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Danko Georgiev

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Danko D. Georgiev earned his M.D. from Medical University of Varna, Bulgaria, in 2004, and his Ph.D. in Pharmaceutical Sciences from Kanazawa University, Japan, in 2008 for his research in the area of neuronal differentiation. He has worked as an anesthesiologist at the Naval Hospital, Varna, and was also a researcher in the Department of Psychiatry and Neurobiology at Kanazawa University, where he studied the molecular alterations in the cerebral cortex of subjects with schizophrenia. He held a two-year JSPS Postdoctoral Fellowship awarded by the Japan Society for the Promotion of Science, and was a short-term visiting scholar at the Department of Psychiatry, University of Pittsburgh. He was then a postdoctoral associate in the Department of Environmental and Occupational Health, University of Pittsburgh, where he studied the pathogenesis and treatment of Alzheimer's disease. Dr. Georgiev is currently a principal investigator at the Institute for Advanced Study, Varna, Bulgaria, where he performs interdisciplinary research on quantum foundations, quantum physics, quantum chemistry, neuroscience, information science and applied mathematics.
Address: Varna, Varna, Bulgaria

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University of Lausanne

University of Delhi

University of Ljubljana, Biotechnical Faculty

Dirk K F Meijer

University of Groningen

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University of Alberta

Physical Studies Institute

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Books by Danko Georgiev

20% Discount flyer "Quantum Information and Consciousness: A Gentle Introduction"

This book addresses the fascinating cross-disciplinary field of quantum information theory applie... more This book addresses the fascinating cross-disciplinary field
of quantum information theory applied to the study of
brain function. It offers a self-study guide to probe the
problems of consciousness, including a concise but rigorous
introduction to classical and quantum information theory,
theoretical neuroscience, and philosophy of the mind. It
aims to address long-standing problems related to
consciousness within the framework of modern theoretical
physics in a comprehensible manner that elucidates the
nature of the mind-body relationship. The reader also gains
an overview of methods for constructing and testing
quantum informational theories of consciousness.

Quantum Information and Consciousness: A Gentle Introduction

This book addresses the fascinating cross-disciplinary field of quantum information theory applie... more This book addresses the fascinating cross-disciplinary field of quantum information theory applied to the study of brain function. It offers a self-study guide to probe the problems of consciousness, including a concise but rigorous introduction to classical and quantum information theory, theoretical neuroscience, and philosophy of the mind. It aims to address long-standing problems related to consciousness within the framework of modern theoretical physics in a comprehensible manner that elucidates the nature of the mind-body relationship. The reader also gains an overview of methods for constructing and testing quantum informational theories of consciousness.

Papers by Danko Georgiev

Quantum information theoretic approach to the mind-brain problem

Progress in Biophysics and Molecular Biology, 2020

The brain is composed of electrically excitable neuronal networks regulated by the activity of vo... more The brain is composed of electrically excitable neuronal networks regulated by the activity of voltage-gated ion channels. Further portraying the molecular composition of the brain, however, will not reveal anything remotely reminiscent of a feeling, a sensation or a conscious experience. In classical physics, addressing the mind-brain problem is a formidable task because no physical mechanism is able to explain how the brain generates the unobservable, inner psychological world of conscious experiences and how in turn those conscious experiences steer the underlying brain processes toward desired behavior. Yet, this setback does not establish that consciousness is non-physical. Modern quantum physics affirms the interplay between two types of physical entities in Hilbert space: unobservable quantum states, which are vectors describing what exists in the physical world, and quantum observables, which are operators describing what can be observed in quantum measurements. Quantum no-go theorems further provide a framework for studying quantum brain dynamics, which has to be governed by a physically admissible Hamiltonian. Comprising consciousness of unobservable quantum information integrated in quantum brain states explains the origin of the inner privacy of conscious experiences and revisits the dynamic timescale of conscious processes to picosecond conformational transitions of neural biomolecules. The observable brain is then an objective construction created from classical bits of information, which are bound by Holevo's theorem, and obtained through the measurement of quantum brain observables. Thus, quantum information theory clarifies the distinction between the unobservable mind and the observable brain, and supports a solid physical foundation for consciousness research. Highlights • Psychological inner world remains private and unobservable from a third-person perspective. • Physiological brain activity due to electric excitations of neuronal networks is observable. • Quantum information theory makes a distinction between physical states and observables. • Unobservable quantum information built in quantum brain states comprises consciousness. • The observable brain is constructed from bits of information constrained by Holevo's theorem.

Enhancing user creativity: Semantic measures for idea generation

Knowledge-Based Systems, 2018

Human creativity generates novel ideas to solve real-world problems. This thereby grants us the p... more Human creativity generates novel ideas to solve real-world problems. This thereby grants us the power to transform the surrounding world and extend our human attributes beyond what is currently possible. Creative ideas are not just new and unexpected, but are also successful in providing solutions that are useful, efficient and valuable. Thus, creativity optimizes the use of available resources and increases wealth. The origin of human creativity, however, is poorly understood, and semantic measures that could predict the success of generated ideas are currently unknown. Here, we analyze a dataset of design problem-solving conversations in real-world settings by using 49 semantic measures based on WordNet 3.1 and demonstrate that a divergence of semantic similarity, an increased information content, and a decreased polysemy predict the success of generated ideas. The first feedback from clients also enhances information content and leads to a divergence of successful ideas in creative problem solving. These results advance cognitive science by identifying real-world processes in human problem solving that are relevant to the success of produced solutions and provide tools for real-time monitoring of problem solving , student training and skill acquisition. A selected subset of information content (IC Sánchez-Batet) and semantic similarity (Lin/Sánchez-Batet) measures, which are both statistically powerful and computation-ally fast, could support the development of technologies for computer-assisted enhancements of human creativity or for the implementation of creativity in machines endowed with general artificial intelligence .

Probing finite coarse-grained virtual Feynman histories with sequential weak values

Physical Review A, 2018

Feynman's sum-over-histories formulation of quantum mechanics has been considered a useful calcul... more Feynman's sum-over-histories formulation of quantum mechanics has been considered a useful calculational tool in which virtual Feynman histories entering into a coherent quantum superpo-sition cannot be individually measured. Here we show that sequential weak values, inferred by consecutive weak measurements of projectors, allow direct experimental probing of individual virtual Feynman histories thereby revealing the exact nature of quantum interference of coherently superposed histories. Because the total sum of sequential weak values of multi-time projection operators for a complete set of orthogonal quantum histories is unity, complete sets of weak values could be interpreted in agreement with the standard quantum mechanical picture. We also elucidate the relationship between sequential weak values of quantum histories with different coarse-graining in time and establish the incompatibility of weak values for non-orthogonal quantum histories in history Hilbert space. Bridging theory and experiment, the presented results may enhance our understanding of both weak values and quantum histories. In this work, we revisit the important yet controversial concept of quantum weak values and elucidate the relationship between Aharonov's two-state vector formalism and Feynman's sum-over-histories. This interesting relationship resonates with past works which studied non-demolition and continuous quantum measurements [1-4], while connecting them with path integration [5]. Recently , the above relationship was further analyzed and strengthened by different researchers [6-11], but here we focus on the notion of sequential weak values as a piv-otal issue, which has not been mentioned before in the above literature. In particular, we show that sequential weak values are able to probe directly the quantum probability amplitudes along individual virtual Feynman histories thereby possibly supporting their physical mean-ingfulness. Conversely, we utilize the mathematical constraints behind Feynman summation in order to provide rules for consistent interpretation of experimentally measured weak values. I. PRELIMINARIES To begin with, we succinctly describe a finite coarse-grained Feynman's sum-over-histories procedure applicable to any experiment performed with a finite precision. Definition 1. (Quantum history) Quantum histories from an initial time t i to a final time t f are constructed at k + 2 different times t i , t 1 , t 2 ,. .. , t k , t f * Electronic address: [email protected] † Electronic address:

On the quantum dynamics of Davydov solitons in protein α-helices

Physica A: Statistical Mechanics and its Applications, 2019

The transport of energy inside protein α-helices is studied by deriving a system of quantum equat... more The transport of energy inside protein α-helices is studied by deriving a system of quantum equations of motion from the Davydov Hamiltonian with the use of the Schrödinger equation and the generalized Ehrenfest theorem. Numerically solving the system of quantum equations of motion for different initial distributions of the amide I energy over the peptide groups confirmed the generation of both moving or stationary Davydov solitons. In this simulation the soliton generation, propagation, and stability were found to be dependent on the symmetry of the exciton-phonon interaction Hamiltonian and the initial site of application of the exciton energy.

Quantum tunneling of Davydov solitons through massive barriers

Chaos, Solitons & Fractals, 2019

Protein clamps provide the cell with effective mechanisms for sensing of environmental changes an... more Protein clamps provide the cell with effective mechanisms for sensing of environmental changes and triggering adaptations that maintain homeostasis. The general physical mechanism behind protein clamping action, however, is poorly understood. Here, we explore the Davydov model for quantum transport of amide I energy, which is self-trapped in soliton states that propagate along the protein α-helix spines and preserve their shape upon reflection from the α-helix ends. We study computationally whether the Davydov solitons are able to reflect from massive barriers that model the presence of external protein clamps acting on a portion of the α-helix, and characterize the range of barrier conditions for which the Davydov solitons are capable of tunneling through the barrier. The simulations showed that the variability of amino acid masses in proteins has a negligible effect on Davydov soliton dynamics, but a massive barrier that is a hundred times the mass of a single amino acid presents an obstacle for the soliton propagation. The greater width of Davydov solitons stabilizes the soliton upon reflection from such a massive barrier and increases the probability of tunneling through it, whereas the greater isotropy of the exciton-lattice coupling suppresses the tunneling efficiency by increasing the interaction time between the Davydov soliton and the barrier, thereby prolonging the tunneling time through the barrier and enhancing the probability for reflection from the latter. The results as presented, demonstrate the feasibility of Davydov solitons reflecting from or tunneling through massive barriers, and suggest a general physical mechanism underlying the action of protein clamps through local enhancement of an effective protein α-helix mass.

Inner privacy of conscious experiences and quantum information

Biosystems, 2020

The human mind is constituted by inner, subjective, private, first-person conscious experiences t... more The human mind is constituted by inner, subjective, private, first-person conscious experiences that cannot be measured with physical devices or observed from an external, objective, public, third-person perspective. The qualitative, phenomenal nature of conscious experiences also cannot be communicated to others in the form of a message composed of classical bits of information. Because in a classical world everything physical is observable and communicable, it is a daunting task to explain how an empirically unobservable, incommunicable consciousness could have any physical substrates such as neurons composed of biochemical molecules, water, and electrolytes. The challenges encountered by classical physics are exemplified by a number of thought experiments including the inverted qualia argument, the private language argument, the beetle in the box argument and the knowledge argument. These thought experiments, however, do not imply that our consciousness is nonphysical and our introspective conscious testimonies are untrustworthy. The principles of classical physics have been superseded by modern quantum physics, which contains two fundamentally different kinds of physical objects: unobservable quantum state vectors, which define what physically exists, and quantum operators (observables), which define what can physically be observed. Identifying consciousness with the unobservable quantum information contained by quantum physical brain states allows for application of quantum information theorems to resolve possible paradoxes created by the inner privacy of conscious experiences, and explains how the observable brain is constructed by accessible bits of classical information that are bound by Holevo's theorem and extracted from the physically existing quantum brain upon measurement with physical devices.

Quantum transport and utilization of free energy in protein α-helices

Advances in Quantum Chemistry, 2020

The essential biological processes that sustain life are catalyzed by protein nano-engines, which... more The essential biological processes that sustain life are catalyzed by protein nano-engines, which maintain living systems in far-from-equilibrium ordered states. To investigate energetic processes in proteins, we have analyzed the system of generalized Davydov equations that govern the quantum dynamics of multiple amide I exciton quanta propagating along the hydrogen-bonded peptide groups in α-helices. Computational simulations have confirmed the generation of moving Davydov solitons by applied pulses of amide I energy for protein α-helices of varying length. The stability and mobility of these solitons depended on the uniformity of dipole-dipole coupling between amide I oscillators, and the isotropy of the exciton-phonon interaction. Davydov solitons were also able to quantum tunnel through massive barriers, or to quantum interfere at collision sites. The results presented here support a non-trivial role of quantum effects in biological systems that lies beyond the mechanistic support of covalent bonds as binding agents of macromolecular structures. Quantum tunneling and interference of Davydov solitons provide catalytically active macromolecular protein complexes with a physical mechanism allowing highly efficient transport, delivery, and utilization of free energy, besides the evolutionary mandate of biological order that supports the existence of such genuine quantum phenomena, and may indeed demarcate the quantum boundaries of life.

Launching of Davydov solitons in protein α-helix spines

Physica E: Low-dimensional Systems and Nanostructures, 2020

The biological order provided by α-helical secondary protein structures is an important resource ... more The biological order provided by α-helical secondary protein structures is an important resource exploitable by living organisms for increasing the efficiency of energy transport. In particular, self-trapping of amide I energy quanta by the induced phonon deformation of the hydrogen-bonded lattice of peptide groups is capable of generating either pinned or moving solitary waves following the Davydov quasiparticle/soliton model. The effect of applied in-phase Gaussian pulses of amide I energy, however, was found to be strongly dependent on the site of application. Moving solitons were only launched when the amide I energy was applied at one of the α-helix ends, whereas pinned solitons were produced in the α-helix interior. In this paper, we describe a general mechanism that launches moving solitons in the interior of the α-helix through phase-modulated Gaussian pulses of amide I energy. We also compare the predicted soliton velocity based on effective soliton mass and the observed soliton velocity in computer simulations for different parameter values of the isotropy of the exciton-phonon interaction. The presented results demonstrate the capacity for explicit control of the soliton velocity in protein α-helices, and further support the plausibility of gradual optimization of quantum dynamics for achieving specialized protein functions through natural selection.

Computational capacity of pyramidal neurons in the cerebral cortex

Brain Research, 2020

The electric activities of cortical pyramidal neurons are supported by structurally stable, morph... more The electric activities of cortical pyramidal neurons are supported by structurally stable, morphologically complex axo-dendritic trees. Anatomical differences between axons and dendrites in regard to their length or caliber reflect the underlying functional specializations, for input or output of neural information, respectively. For a proper assessment of the computational capacity of pyramidal neurons, we have analyzed an extensive dataset of three-dimensional digital reconstructions from the NeuroMorpho.Org database, and quantified basic dendritic or axonal morphometric measures in different regions and layers of the mouse, rat or human cerebral cortex. Physical estimates of the total number and type of ions involved in neuronal electric spiking based on the obtained morphometric data, combined with energetics of neurotransmitter release and signaling fueled by glucose consumed by the active brain, support highly efficient cerebral computation performed at the thermodynamically allowed Landauer limit for implementation of irreversible logical operations. Individual proton tunneling events in voltage-sensing S4 protein α-helices of Na + , K + or Ca 2+ ion channels are ideally suited to serve as single Landauer elementary logical operations that are then amplified by selective ionic currents traversing the open channel pores. This miniaturization of computational gating allows the execution of over 1.2 zetta logical operations per second in the human cerebral cortex without combusting the brain by the released heat.

Lower Gene Expression for KCNS3 Potassium Channel Subunit in Parvalbumin-Containing Neurons in the Prefrontal Cortex in Schizophrenia

American Journal of Psychiatry, 2014

OBJECTIVE: In schizophrenia, alterations in markers of cortical GABA neurotransmission are promin... more OBJECTIVE: In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent in parvalbumin-containing neurons. Parvalbumin neurons selectively express KCNS3, the gene encoding the Kv9.3 potassium channel α-subunit. Kv9.3 subunits are present in voltage-gated potassium channels that contribute to the precise detection of coincident excitatory synaptic inputs to parvalbumin neurons. This distinctive feature of parvalbumin neurons appears important for the synchronization of cortical neural networks in γ-oscillations. Because impaired prefrontal cortical γ-oscillations are thought to underlie the cognitive impairments in schizophrenia, the authors investigated whether KCNS3 mRNA levels are altered in the prefrontal cortex of schizophrenia subjects.
METHOD: KCNS3 mRNA expression was evaluated by in situ hybridization in 22 matched pairs of schizophrenia and comparison subjects and by microarray analyses of pooled samples of individually dissected neurons that were labeled with Vicia villosa agglutinin (VVA), a parvalbumin neuron-selective marker, in a separate cohort of 14 pairs. Effects of chronic antipsychotic treatments on KCNS3 expression were tested in the prefrontal cortex of antipsychotic-exposed monkeys.
RESULTS: By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower. By microarray, KCNS3 mRNA levels were lower by 40% in VVA-labeled neurons from schizophrenia subjects. KCNS3 mRNA levels were not altered in antipsychotic-exposed monkeys.
CONCLUSIONS: These findings reveal lower KCNS3 expression in prefrontal cortical parvalbumin neurons in schizophrenia, providing a molecular basis for compromised detection of coincident synaptic inputs to parvalbumin neurons that could contribute to altered γ-oscillations and impaired cognition in schizophrenia.

Selective Expression of KCNS3 Potassium Channel α-Subunit in Parvalbumin-Containing GABA Neurons in the Human Prefrontal Cortex

PLoS ONE, 2012

The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurot... more The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV) or somatostatin (SST). Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K+ channel Kv9.3 modulatory α-subunit, LIM homeobox protein 6, K+ channel Kvβ1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with 35S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia.

A critical importance of polyamine site in NMDA receptors for neurite outgrowth and fasciculation at early stages of P19 neuronal differentiation

Experimental Cell Research, 2008

We have investigated the role of N-methyl-d-aspartate receptors (NMDARs) and gamma-aminobutyric a... more We have investigated the role of N-methyl-d-aspartate receptors (NMDARs) and gamma-aminobutyric acid receptors type A (GABA(A)Rs) at an early stage of P19 neuronal differentiation. The subunit expression was profiled in 24-hour intervals with RT-PCR and functionality of the receptors was verified via fluo-3 imaging of Ca(2+) dynamics in the immature P19 neurons showing that both NMDA and GABA excite neuronal bodies, but only polyamine-site sensitive NMDAR stimulation leads to enhanced Ca(2+) signaling in the growth cones. Inhibition of NR1/NR2B NMDARs by 1 muM ifenprodil severely impaired P19 neurite extension and fasciculation, and this negative effect was fully reversible by polyamine addition. In contrast, GABA(A)R antagonism by a high dose of 200 microM bicuculline had no observable effect on P19 neuronal differentiation and fasciculation. Except for the differential NMDAR and GABA(A)R profiles of Ca(2+) signaling within the immature P19 neurons, we have also shown that inhibition of NR1/NR2B NMDARs strongly decreased mRNA level of NCAM-180, which has been previously implicated as a regulator of neuronal growth cone protrusion and neurite extension. Our data thus suggest a critical role of NR1/NR2B NMDARs during the process of neuritogenesis and fasciculation of P19 neurons via differential control of local growth cone Ca(2+) surges and NCAM-180 signaling.

Promotion of neuronal differentiation through activation of N-methyl-D-aspartate receptors transiently expressed by undifferentiated neural progenitor cells in fetal rat neocortex

by Danko Georgiev and Masanori Yoneyama

Journal of Neuroscience Research, 2008

Neural progenitor cell is a generic term for undifferentiated cell populations composed of neural... more Neural progenitor cell is a generic term for undifferentiated cell populations composed of neural stem, neuronal progenitor, and glial progenitor cells with abilities for self-renewal and multipotentiality. In this study, we have attempted to evaluate the possible functional expression of N-methyl-D-aspartate (NMDA) receptors by neural progenitor cells prepared from neocortex of 18-day-old embryonic rats. Cells were cultured in the presence of basic ﬁbroblast growth factor (bFGF) for different periods up to 12 days under ﬂoating conditions. Reverse transcription-polymerase chain reaction and ﬂuorescence imaging analyses revealed transient expression of functional NMDA receptors in neurospheres formed by clustered progenitors during the culture with bFGF. A similarly potent increase was seen in the ﬂuorescence intensity after brief exposure to NMDA in cells differentiated after the removal of bFGF under adherent conditions, and an NMDA receptor antagonist invariably prevented these increases by NMDA. Moreover, sustained exposure to NMDA not only inhibited the formation of neurospheres when exposed for 10 days from day 2 to day 12 but also promoted spontaneous and induced differentiation of neurospheres to cells immunoreactive for a neuronal marker protein on immunocytochemistry and Western blotting analyses. These results suggest that functional NMDA receptors may be transiently expressed to play a role in mechanisms underlying the modulation of proliferation along with the determination of subsequent differentiation fate toward a neuronal lineage in neural progenitor cells of developing rat neocortex.

Insensitivity to glutamate neurotoxicity mediated by NMDA receptors in association with delayed mitochondrial membrane potential disruption in cultured rat cortical neurons

Journal of Neurochemistry, 2008

We have attempted to elucidate mechanisms underlying differential vulnerability to glutamate (Glu... more We have attempted to elucidate mechanisms underlying differential vulnerability to glutamate (Glu) using cultured neurons prepared from discrete structures of embryonic rat brains. Brief exposure to Glu led to a significant decrease in the mitochondrial activity in hippocampal neurons cultured for 9 or 12 days at 10 μM to 1 mM with an apoptosis-like profile, without markedly affecting that in cortical neurons. Brief exposure to Glu also increased lactate dehydrogenase release along with a marked decrease in the number of cells immunoreactive for a neuronal marker protein in hippocampal, but not cortical, neurons. Similar insensitivity was seen to the cytotoxicity by NMDA, but not to that by tunicamycin, 2,4-dinitrophenol, hydrogen peroxide or A23187, in cortical neurons. However, NMDA was more efficient in increasing intracellular free Ca2+ levels in cortical neurons than in hippocampal neurons. Antagonists for neuroprotective metabotropic Glu receptors failed to significantly affect the insensitivity to Glu, while NMDA was more effective in disrupting mitochondrial membrane potentials in hippocampal than cortical neurons. These results suggest that cortical neurons would be insensitive to the apoptotic neurotoxicity mediated by NMDA receptors through a mechanism related to mitochondrial membrane potentials, rather than intracellular free Ca2+ levels, in the rat brain.

Crosstalk between brain-derived neurotrophic factor and N-methyl-D-aspartate receptor signaling in neurons

Biomedical Reviews, 2008

Glutamate is the major excitatory neurotransmitter in brain exerting prosurvival effect on neuron... more Glutamate is the major excitatory neurotransmitter in brain exerting prosurvival effect on neurons via N-methyl-D-aspartate receptor (NMDAR) signaling under physiological conditions. However in pathological circumstances such as ischemia, NMDARs might have proapoptotic excitotoxic activity. In contrast brain-derived neurotrophic factor (BDNF) signaling via tropomyosinrelated receptor kinase B (TrkB) has been largely considered to promote neuronal differentiation, plasticity and survival during normal development, and protect neurons in pathophysiological conditions antagonizing the NMDAR-mediated excitotoxic cell death. In this review we summarize recent evidence for the existent crosstalk and positive feedback loops between the BDNF and NMDAR signaling and point out some of the important specific features of each signaling pathway.

Tex261 modulates the excitotoxic cell death induced by N-methyl-d-aspartate (NMDA) receptor activation

Biochemical and Biophysical Research Communications, 2007

N-methyl-D-aspartate (NMDA) receptor is a calcium-permeable ionotropic glutamate receptor and pla... more N-methyl-D-aspartate (NMDA) receptor is a calcium-permeable ionotropic glutamate receptor and plays a role in many neurologic disorders such as brain ischemia through its involvement in excitotoxicity. We have performed differential display PCR to identify changes in gene expression that occur in the hippocampus of the mouse brain after intraperitoneal injection of NMDA and identified a gene, Tex261 as an inducible gene by NMDA stimulation in vivo. Tex261 mRNA was gradually induced in response to NMDA and reached about 4.5-fold at 24 h. When HEK 293 cells are transfected with NMDA receptors, the cells die in a manner that mimics excitotoxicity in neurons. HEK 293 cells transfected with the combination of Tex261 and the NMDA receptors NR1/NR2A produced the greater cell death compared with the cells transfected with the NMDA receptors alone. These findings suggest that Tex261 modulates the excitotoxic cell death induced by NMDA receptor activation.

Quantum No-Go Theorems and Consciousness

Axiomathes, 2013

Our conscious minds exist in the Universe, therefore they should be identified with physical stat... more Our conscious minds exist in the Universe, therefore they should be identified with physical states that are subject to physical laws. In classical theories of mind, the mental states are identified with brain states that satisfy the deterministic laws of classical mechanics. This approach, however, leads to insurmountable paradoxes such as epiphenomenal minds and illusionary free will. Alternatively, one may identify mental states with quantum states realized within the brain and try to resolve the above paradoxes using the standard Hilbert space formalism of quantum mechanics. In this essay, we first show that identification of mind states with quantum states within the brain is biologically feasible, and then elaborating on the mathematical proofs of two quantum mechanical no-go theorems, we explain why quantum theory might have profound implications for the scientific understanding of one’s mental states, self identity, beliefs and free will.

SNARE proteins as molecular masters of interneuronal communication

Biomedical Reviews, 2010

In the beginning of the 20th century the groundbreaking work of Ramon y Cajal firmly established ... more In the beginning of the 20th century the groundbreaking work of Ramon y Cajal firmly established the neuron doctrine, according to which neurons are the basic structural and functional units of the nervous system. Von Weldeyer coined the term "neuron" in 1891, but the huge leap forward in neuroscience was due to Cajal's meticulous microscopic observations of brain sections stained with an improved version of Golgi's la reazione nera (black reaction). The latter improvement of Golgi's technique made it possible to visualize the arborizations of single neurons that were "colored brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink". The high quality of both the visualization of individual nerve cells and the work performed on studying the anatomy of the central nervous system lead Ramon y Cajal to the conclusion that axons output the nervous impulses to the dendrites or the soma of other target neurons. The name "dendrite" was coined by His in 1889 and "axon" by von Kölliker in 1896, but it was Ramon y Cajal who developed and provided extensive anatomical evidence for the idea that neurons are dynamically polarized and within each neuron the transmission of information is from the dendrites towards the axon.

20% Discount flyer "Quantum Information and Consciousness: A Gentle Introduction"

This book addresses the fascinating cross-disciplinary field of quantum information theory applie... more This book addresses the fascinating cross-disciplinary field
of quantum information theory applied to the study of
brain function. It offers a self-study guide to probe the
problems of consciousness, including a concise but rigorous
introduction to classical and quantum information theory,
theoretical neuroscience, and philosophy of the mind. It
aims to address long-standing problems related to
consciousness within the framework of modern theoretical
physics in a comprehensible manner that elucidates the
nature of the mind-body relationship. The reader also gains
an overview of methods for constructing and testing
quantum informational theories of consciousness.

Quantum Information and Consciousness: A Gentle Introduction

This book addresses the fascinating cross-disciplinary field of quantum information theory applie... more This book addresses the fascinating cross-disciplinary field of quantum information theory applied to the study of brain function. It offers a self-study guide to probe the problems of consciousness, including a concise but rigorous introduction to classical and quantum information theory, theoretical neuroscience, and philosophy of the mind. It aims to address long-standing problems related to consciousness within the framework of modern theoretical physics in a comprehensible manner that elucidates the nature of the mind-body relationship. The reader also gains an overview of methods for constructing and testing quantum informational theories of consciousness.

Quantum information theoretic approach to the mind-brain problem

Progress in Biophysics and Molecular Biology, 2020

The brain is composed of electrically excitable neuronal networks regulated by the activity of vo... more The brain is composed of electrically excitable neuronal networks regulated by the activity of voltage-gated ion channels. Further portraying the molecular composition of the brain, however, will not reveal anything remotely reminiscent of a feeling, a sensation or a conscious experience. In classical physics, addressing the mind-brain problem is a formidable task because no physical mechanism is able to explain how the brain generates the unobservable, inner psychological world of conscious experiences and how in turn those conscious experiences steer the underlying brain processes toward desired behavior. Yet, this setback does not establish that consciousness is non-physical. Modern quantum physics affirms the interplay between two types of physical entities in Hilbert space: unobservable quantum states, which are vectors describing what exists in the physical world, and quantum observables, which are operators describing what can be observed in quantum measurements. Quantum no-go theorems further provide a framework for studying quantum brain dynamics, which has to be governed by a physically admissible Hamiltonian. Comprising consciousness of unobservable quantum information integrated in quantum brain states explains the origin of the inner privacy of conscious experiences and revisits the dynamic timescale of conscious processes to picosecond conformational transitions of neural biomolecules. The observable brain is then an objective construction created from classical bits of information, which are bound by Holevo's theorem, and obtained through the measurement of quantum brain observables. Thus, quantum information theory clarifies the distinction between the unobservable mind and the observable brain, and supports a solid physical foundation for consciousness research. Highlights • Psychological inner world remains private and unobservable from a third-person perspective. • Physiological brain activity due to electric excitations of neuronal networks is observable. • Quantum information theory makes a distinction between physical states and observables. • Unobservable quantum information built in quantum brain states comprises consciousness. • The observable brain is constructed from bits of information constrained by Holevo's theorem.

Enhancing user creativity: Semantic measures for idea generation

Knowledge-Based Systems, 2018

Human creativity generates novel ideas to solve real-world problems. This thereby grants us the p... more Human creativity generates novel ideas to solve real-world problems. This thereby grants us the power to transform the surrounding world and extend our human attributes beyond what is currently possible. Creative ideas are not just new and unexpected, but are also successful in providing solutions that are useful, efficient and valuable. Thus, creativity optimizes the use of available resources and increases wealth. The origin of human creativity, however, is poorly understood, and semantic measures that could predict the success of generated ideas are currently unknown. Here, we analyze a dataset of design problem-solving conversations in real-world settings by using 49 semantic measures based on WordNet 3.1 and demonstrate that a divergence of semantic similarity, an increased information content, and a decreased polysemy predict the success of generated ideas. The first feedback from clients also enhances information content and leads to a divergence of successful ideas in creative problem solving. These results advance cognitive science by identifying real-world processes in human problem solving that are relevant to the success of produced solutions and provide tools for real-time monitoring of problem solving , student training and skill acquisition. A selected subset of information content (IC Sánchez-Batet) and semantic similarity (Lin/Sánchez-Batet) measures, which are both statistically powerful and computation-ally fast, could support the development of technologies for computer-assisted enhancements of human creativity or for the implementation of creativity in machines endowed with general artificial intelligence .

Probing finite coarse-grained virtual Feynman histories with sequential weak values

Physical Review A, 2018

Feynman's sum-over-histories formulation of quantum mechanics has been considered a useful calcul... more Feynman's sum-over-histories formulation of quantum mechanics has been considered a useful calculational tool in which virtual Feynman histories entering into a coherent quantum superpo-sition cannot be individually measured. Here we show that sequential weak values, inferred by consecutive weak measurements of projectors, allow direct experimental probing of individual virtual Feynman histories thereby revealing the exact nature of quantum interference of coherently superposed histories. Because the total sum of sequential weak values of multi-time projection operators for a complete set of orthogonal quantum histories is unity, complete sets of weak values could be interpreted in agreement with the standard quantum mechanical picture. We also elucidate the relationship between sequential weak values of quantum histories with different coarse-graining in time and establish the incompatibility of weak values for non-orthogonal quantum histories in history Hilbert space. Bridging theory and experiment, the presented results may enhance our understanding of both weak values and quantum histories. In this work, we revisit the important yet controversial concept of quantum weak values and elucidate the relationship between Aharonov's two-state vector formalism and Feynman's sum-over-histories. This interesting relationship resonates with past works which studied non-demolition and continuous quantum measurements [1-4], while connecting them with path integration [5]. Recently , the above relationship was further analyzed and strengthened by different researchers [6-11], but here we focus on the notion of sequential weak values as a piv-otal issue, which has not been mentioned before in the above literature. In particular, we show that sequential weak values are able to probe directly the quantum probability amplitudes along individual virtual Feynman histories thereby possibly supporting their physical mean-ingfulness. Conversely, we utilize the mathematical constraints behind Feynman summation in order to provide rules for consistent interpretation of experimentally measured weak values. I. PRELIMINARIES To begin with, we succinctly describe a finite coarse-grained Feynman's sum-over-histories procedure applicable to any experiment performed with a finite precision. Definition 1. (Quantum history) Quantum histories from an initial time t i to a final time t f are constructed at k + 2 different times t i , t 1 , t 2 ,. .. , t k , t f * Electronic address: [email protected] † Electronic address:

On the quantum dynamics of Davydov solitons in protein α-helices

Physica A: Statistical Mechanics and its Applications, 2019

The transport of energy inside protein α-helices is studied by deriving a system of quantum equat... more The transport of energy inside protein α-helices is studied by deriving a system of quantum equations of motion from the Davydov Hamiltonian with the use of the Schrödinger equation and the generalized Ehrenfest theorem. Numerically solving the system of quantum equations of motion for different initial distributions of the amide I energy over the peptide groups confirmed the generation of both moving or stationary Davydov solitons. In this simulation the soliton generation, propagation, and stability were found to be dependent on the symmetry of the exciton-phonon interaction Hamiltonian and the initial site of application of the exciton energy.

Quantum tunneling of Davydov solitons through massive barriers

Chaos, Solitons & Fractals, 2019

Protein clamps provide the cell with effective mechanisms for sensing of environmental changes an... more Protein clamps provide the cell with effective mechanisms for sensing of environmental changes and triggering adaptations that maintain homeostasis. The general physical mechanism behind protein clamping action, however, is poorly understood. Here, we explore the Davydov model for quantum transport of amide I energy, which is self-trapped in soliton states that propagate along the protein α-helix spines and preserve their shape upon reflection from the α-helix ends. We study computationally whether the Davydov solitons are able to reflect from massive barriers that model the presence of external protein clamps acting on a portion of the α-helix, and characterize the range of barrier conditions for which the Davydov solitons are capable of tunneling through the barrier. The simulations showed that the variability of amino acid masses in proteins has a negligible effect on Davydov soliton dynamics, but a massive barrier that is a hundred times the mass of a single amino acid presents an obstacle for the soliton propagation. The greater width of Davydov solitons stabilizes the soliton upon reflection from such a massive barrier and increases the probability of tunneling through it, whereas the greater isotropy of the exciton-lattice coupling suppresses the tunneling efficiency by increasing the interaction time between the Davydov soliton and the barrier, thereby prolonging the tunneling time through the barrier and enhancing the probability for reflection from the latter. The results as presented, demonstrate the feasibility of Davydov solitons reflecting from or tunneling through massive barriers, and suggest a general physical mechanism underlying the action of protein clamps through local enhancement of an effective protein α-helix mass.

Inner privacy of conscious experiences and quantum information

Biosystems, 2020

The human mind is constituted by inner, subjective, private, first-person conscious experiences t... more The human mind is constituted by inner, subjective, private, first-person conscious experiences that cannot be measured with physical devices or observed from an external, objective, public, third-person perspective. The qualitative, phenomenal nature of conscious experiences also cannot be communicated to others in the form of a message composed of classical bits of information. Because in a classical world everything physical is observable and communicable, it is a daunting task to explain how an empirically unobservable, incommunicable consciousness could have any physical substrates such as neurons composed of biochemical molecules, water, and electrolytes. The challenges encountered by classical physics are exemplified by a number of thought experiments including the inverted qualia argument, the private language argument, the beetle in the box argument and the knowledge argument. These thought experiments, however, do not imply that our consciousness is nonphysical and our introspective conscious testimonies are untrustworthy. The principles of classical physics have been superseded by modern quantum physics, which contains two fundamentally different kinds of physical objects: unobservable quantum state vectors, which define what physically exists, and quantum operators (observables), which define what can physically be observed. Identifying consciousness with the unobservable quantum information contained by quantum physical brain states allows for application of quantum information theorems to resolve possible paradoxes created by the inner privacy of conscious experiences, and explains how the observable brain is constructed by accessible bits of classical information that are bound by Holevo's theorem and extracted from the physically existing quantum brain upon measurement with physical devices.

Quantum transport and utilization of free energy in protein α-helices

Advances in Quantum Chemistry, 2020

The essential biological processes that sustain life are catalyzed by protein nano-engines, which... more The essential biological processes that sustain life are catalyzed by protein nano-engines, which maintain living systems in far-from-equilibrium ordered states. To investigate energetic processes in proteins, we have analyzed the system of generalized Davydov equations that govern the quantum dynamics of multiple amide I exciton quanta propagating along the hydrogen-bonded peptide groups in α-helices. Computational simulations have confirmed the generation of moving Davydov solitons by applied pulses of amide I energy for protein α-helices of varying length. The stability and mobility of these solitons depended on the uniformity of dipole-dipole coupling between amide I oscillators, and the isotropy of the exciton-phonon interaction. Davydov solitons were also able to quantum tunnel through massive barriers, or to quantum interfere at collision sites. The results presented here support a non-trivial role of quantum effects in biological systems that lies beyond the mechanistic support of covalent bonds as binding agents of macromolecular structures. Quantum tunneling and interference of Davydov solitons provide catalytically active macromolecular protein complexes with a physical mechanism allowing highly efficient transport, delivery, and utilization of free energy, besides the evolutionary mandate of biological order that supports the existence of such genuine quantum phenomena, and may indeed demarcate the quantum boundaries of life.

Launching of Davydov solitons in protein α-helix spines

Physica E: Low-dimensional Systems and Nanostructures, 2020

The biological order provided by α-helical secondary protein structures is an important resource ... more The biological order provided by α-helical secondary protein structures is an important resource exploitable by living organisms for increasing the efficiency of energy transport. In particular, self-trapping of amide I energy quanta by the induced phonon deformation of the hydrogen-bonded lattice of peptide groups is capable of generating either pinned or moving solitary waves following the Davydov quasiparticle/soliton model. The effect of applied in-phase Gaussian pulses of amide I energy, however, was found to be strongly dependent on the site of application. Moving solitons were only launched when the amide I energy was applied at one of the α-helix ends, whereas pinned solitons were produced in the α-helix interior. In this paper, we describe a general mechanism that launches moving solitons in the interior of the α-helix through phase-modulated Gaussian pulses of amide I energy. We also compare the predicted soliton velocity based on effective soliton mass and the observed soliton velocity in computer simulations for different parameter values of the isotropy of the exciton-phonon interaction. The presented results demonstrate the capacity for explicit control of the soliton velocity in protein α-helices, and further support the plausibility of gradual optimization of quantum dynamics for achieving specialized protein functions through natural selection.

Computational capacity of pyramidal neurons in the cerebral cortex

Brain Research, 2020

The electric activities of cortical pyramidal neurons are supported by structurally stable, morph... more The electric activities of cortical pyramidal neurons are supported by structurally stable, morphologically complex axo-dendritic trees. Anatomical differences between axons and dendrites in regard to their length or caliber reflect the underlying functional specializations, for input or output of neural information, respectively. For a proper assessment of the computational capacity of pyramidal neurons, we have analyzed an extensive dataset of three-dimensional digital reconstructions from the NeuroMorpho.Org database, and quantified basic dendritic or axonal morphometric measures in different regions and layers of the mouse, rat or human cerebral cortex. Physical estimates of the total number and type of ions involved in neuronal electric spiking based on the obtained morphometric data, combined with energetics of neurotransmitter release and signaling fueled by glucose consumed by the active brain, support highly efficient cerebral computation performed at the thermodynamically allowed Landauer limit for implementation of irreversible logical operations. Individual proton tunneling events in voltage-sensing S4 protein α-helices of Na + , K + or Ca 2+ ion channels are ideally suited to serve as single Landauer elementary logical operations that are then amplified by selective ionic currents traversing the open channel pores. This miniaturization of computational gating allows the execution of over 1.2 zetta logical operations per second in the human cerebral cortex without combusting the brain by the released heat.

Lower Gene Expression for KCNS3 Potassium Channel Subunit in Parvalbumin-Containing Neurons in the Prefrontal Cortex in Schizophrenia

American Journal of Psychiatry, 2014

OBJECTIVE: In schizophrenia, alterations in markers of cortical GABA neurotransmission are promin... more OBJECTIVE: In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent in parvalbumin-containing neurons. Parvalbumin neurons selectively express KCNS3, the gene encoding the Kv9.3 potassium channel α-subunit. Kv9.3 subunits are present in voltage-gated potassium channels that contribute to the precise detection of coincident excitatory synaptic inputs to parvalbumin neurons. This distinctive feature of parvalbumin neurons appears important for the synchronization of cortical neural networks in γ-oscillations. Because impaired prefrontal cortical γ-oscillations are thought to underlie the cognitive impairments in schizophrenia, the authors investigated whether KCNS3 mRNA levels are altered in the prefrontal cortex of schizophrenia subjects.
METHOD: KCNS3 mRNA expression was evaluated by in situ hybridization in 22 matched pairs of schizophrenia and comparison subjects and by microarray analyses of pooled samples of individually dissected neurons that were labeled with Vicia villosa agglutinin (VVA), a parvalbumin neuron-selective marker, in a separate cohort of 14 pairs. Effects of chronic antipsychotic treatments on KCNS3 expression were tested in the prefrontal cortex of antipsychotic-exposed monkeys.
RESULTS: By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower. By microarray, KCNS3 mRNA levels were lower by 40% in VVA-labeled neurons from schizophrenia subjects. KCNS3 mRNA levels were not altered in antipsychotic-exposed monkeys.
CONCLUSIONS: These findings reveal lower KCNS3 expression in prefrontal cortical parvalbumin neurons in schizophrenia, providing a molecular basis for compromised detection of coincident synaptic inputs to parvalbumin neurons that could contribute to altered γ-oscillations and impaired cognition in schizophrenia.

Selective Expression of KCNS3 Potassium Channel α-Subunit in Parvalbumin-Containing GABA Neurons in the Human Prefrontal Cortex

PLoS ONE, 2012

The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurot... more The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV) or somatostatin (SST). Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K+ channel Kv9.3 modulatory α-subunit, LIM homeobox protein 6, K+ channel Kvβ1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with 35S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia.

A critical importance of polyamine site in NMDA receptors for neurite outgrowth and fasciculation at early stages of P19 neuronal differentiation

Experimental Cell Research, 2008

We have investigated the role of N-methyl-d-aspartate receptors (NMDARs) and gamma-aminobutyric a... more We have investigated the role of N-methyl-d-aspartate receptors (NMDARs) and gamma-aminobutyric acid receptors type A (GABA(A)Rs) at an early stage of P19 neuronal differentiation. The subunit expression was profiled in 24-hour intervals with RT-PCR and functionality of the receptors was verified via fluo-3 imaging of Ca(2+) dynamics in the immature P19 neurons showing that both NMDA and GABA excite neuronal bodies, but only polyamine-site sensitive NMDAR stimulation leads to enhanced Ca(2+) signaling in the growth cones. Inhibition of NR1/NR2B NMDARs by 1 muM ifenprodil severely impaired P19 neurite extension and fasciculation, and this negative effect was fully reversible by polyamine addition. In contrast, GABA(A)R antagonism by a high dose of 200 microM bicuculline had no observable effect on P19 neuronal differentiation and fasciculation. Except for the differential NMDAR and GABA(A)R profiles of Ca(2+) signaling within the immature P19 neurons, we have also shown that inhibition of NR1/NR2B NMDARs strongly decreased mRNA level of NCAM-180, which has been previously implicated as a regulator of neuronal growth cone protrusion and neurite extension. Our data thus suggest a critical role of NR1/NR2B NMDARs during the process of neuritogenesis and fasciculation of P19 neurons via differential control of local growth cone Ca(2+) surges and NCAM-180 signaling.

Promotion of neuronal differentiation through activation of N-methyl-D-aspartate receptors transiently expressed by undifferentiated neural progenitor cells in fetal rat neocortex

by Danko Georgiev and Masanori Yoneyama

Journal of Neuroscience Research, 2008

Neural progenitor cell is a generic term for undifferentiated cell populations composed of neural... more Neural progenitor cell is a generic term for undifferentiated cell populations composed of neural stem, neuronal progenitor, and glial progenitor cells with abilities for self-renewal and multipotentiality. In this study, we have attempted to evaluate the possible functional expression of N-methyl-D-aspartate (NMDA) receptors by neural progenitor cells prepared from neocortex of 18-day-old embryonic rats. Cells were cultured in the presence of basic ﬁbroblast growth factor (bFGF) for different periods up to 12 days under ﬂoating conditions. Reverse transcription-polymerase chain reaction and ﬂuorescence imaging analyses revealed transient expression of functional NMDA receptors in neurospheres formed by clustered progenitors during the culture with bFGF. A similarly potent increase was seen in the ﬂuorescence intensity after brief exposure to NMDA in cells differentiated after the removal of bFGF under adherent conditions, and an NMDA receptor antagonist invariably prevented these increases by NMDA. Moreover, sustained exposure to NMDA not only inhibited the formation of neurospheres when exposed for 10 days from day 2 to day 12 but also promoted spontaneous and induced differentiation of neurospheres to cells immunoreactive for a neuronal marker protein on immunocytochemistry and Western blotting analyses. These results suggest that functional NMDA receptors may be transiently expressed to play a role in mechanisms underlying the modulation of proliferation along with the determination of subsequent differentiation fate toward a neuronal lineage in neural progenitor cells of developing rat neocortex.

Insensitivity to glutamate neurotoxicity mediated by NMDA receptors in association with delayed mitochondrial membrane potential disruption in cultured rat cortical neurons

Journal of Neurochemistry, 2008

We have attempted to elucidate mechanisms underlying differential vulnerability to glutamate (Glu... more We have attempted to elucidate mechanisms underlying differential vulnerability to glutamate (Glu) using cultured neurons prepared from discrete structures of embryonic rat brains. Brief exposure to Glu led to a significant decrease in the mitochondrial activity in hippocampal neurons cultured for 9 or 12 days at 10 μM to 1 mM with an apoptosis-like profile, without markedly affecting that in cortical neurons. Brief exposure to Glu also increased lactate dehydrogenase release along with a marked decrease in the number of cells immunoreactive for a neuronal marker protein in hippocampal, but not cortical, neurons. Similar insensitivity was seen to the cytotoxicity by NMDA, but not to that by tunicamycin, 2,4-dinitrophenol, hydrogen peroxide or A23187, in cortical neurons. However, NMDA was more efficient in increasing intracellular free Ca2+ levels in cortical neurons than in hippocampal neurons. Antagonists for neuroprotective metabotropic Glu receptors failed to significantly affect the insensitivity to Glu, while NMDA was more effective in disrupting mitochondrial membrane potentials in hippocampal than cortical neurons. These results suggest that cortical neurons would be insensitive to the apoptotic neurotoxicity mediated by NMDA receptors through a mechanism related to mitochondrial membrane potentials, rather than intracellular free Ca2+ levels, in the rat brain.

Crosstalk between brain-derived neurotrophic factor and N-methyl-D-aspartate receptor signaling in neurons

Biomedical Reviews, 2008

Glutamate is the major excitatory neurotransmitter in brain exerting prosurvival effect on neuron... more Glutamate is the major excitatory neurotransmitter in brain exerting prosurvival effect on neurons via N-methyl-D-aspartate receptor (NMDAR) signaling under physiological conditions. However in pathological circumstances such as ischemia, NMDARs might have proapoptotic excitotoxic activity. In contrast brain-derived neurotrophic factor (BDNF) signaling via tropomyosinrelated receptor kinase B (TrkB) has been largely considered to promote neuronal differentiation, plasticity and survival during normal development, and protect neurons in pathophysiological conditions antagonizing the NMDAR-mediated excitotoxic cell death. In this review we summarize recent evidence for the existent crosstalk and positive feedback loops between the BDNF and NMDAR signaling and point out some of the important specific features of each signaling pathway.

Tex261 modulates the excitotoxic cell death induced by N-methyl-d-aspartate (NMDA) receptor activation

Biochemical and Biophysical Research Communications, 2007

N-methyl-D-aspartate (NMDA) receptor is a calcium-permeable ionotropic glutamate receptor and pla... more N-methyl-D-aspartate (NMDA) receptor is a calcium-permeable ionotropic glutamate receptor and plays a role in many neurologic disorders such as brain ischemia through its involvement in excitotoxicity. We have performed differential display PCR to identify changes in gene expression that occur in the hippocampus of the mouse brain after intraperitoneal injection of NMDA and identified a gene, Tex261 as an inducible gene by NMDA stimulation in vivo. Tex261 mRNA was gradually induced in response to NMDA and reached about 4.5-fold at 24 h. When HEK 293 cells are transfected with NMDA receptors, the cells die in a manner that mimics excitotoxicity in neurons. HEK 293 cells transfected with the combination of Tex261 and the NMDA receptors NR1/NR2A produced the greater cell death compared with the cells transfected with the NMDA receptors alone. These findings suggest that Tex261 modulates the excitotoxic cell death induced by NMDA receptor activation.

Quantum No-Go Theorems and Consciousness

Axiomathes, 2013

Our conscious minds exist in the Universe, therefore they should be identified with physical stat... more Our conscious minds exist in the Universe, therefore they should be identified with physical states that are subject to physical laws. In classical theories of mind, the mental states are identified with brain states that satisfy the deterministic laws of classical mechanics. This approach, however, leads to insurmountable paradoxes such as epiphenomenal minds and illusionary free will. Alternatively, one may identify mental states with quantum states realized within the brain and try to resolve the above paradoxes using the standard Hilbert space formalism of quantum mechanics. In this essay, we first show that identification of mind states with quantum states within the brain is biologically feasible, and then elaborating on the mathematical proofs of two quantum mechanical no-go theorems, we explain why quantum theory might have profound implications for the scientific understanding of one’s mental states, self identity, beliefs and free will.

SNARE proteins as molecular masters of interneuronal communication

Biomedical Reviews, 2010

In the beginning of the 20th century the groundbreaking work of Ramon y Cajal firmly established ... more In the beginning of the 20th century the groundbreaking work of Ramon y Cajal firmly established the neuron doctrine, according to which neurons are the basic structural and functional units of the nervous system. Von Weldeyer coined the term "neuron" in 1891, but the huge leap forward in neuroscience was due to Cajal's meticulous microscopic observations of brain sections stained with an improved version of Golgi's la reazione nera (black reaction). The latter improvement of Golgi's technique made it possible to visualize the arborizations of single neurons that were "colored brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink". The high quality of both the visualization of individual nerve cells and the work performed on studying the anatomy of the central nervous system lead Ramon y Cajal to the conclusion that axons output the nervous impulses to the dendrites or the soma of other target neurons. The name "dendrite" was coined by His in 1889 and "axon" by von Kölliker in 1896, but it was Ramon y Cajal who developed and provided extensive anatomical evidence for the idea that neurons are dynamically polarized and within each neuron the transmission of information is from the dendrites towards the axon.

Quantum Histories and Quantum Complementarity

ISRN Mathematical Physics, 2012

We discuss the origin of quantum complementarity using Feynman's sum-over-histories approach to Q... more We discuss the origin of quantum complementarity using Feynman's sum-over-histories approach to Quantum Mechanics (QM). We analyze two experimental setups introduced by W. G. Unruh and S. Afshar and show how one should consistently calculate the existence of which-way information using interfering quantum histories. Then we discuss the possible problems associated with the notion of which way information and provide an explanation why Englert-Greenberger duality relation cannot be violated experimentally if the standard QM postulates are accepted.