Papers by Anita Cybulska-Klosowicz
Acta neurobiologiae experimentalis, 2001
An adaptation of roughness discrimination task successfully used on rats was performed on mice. I... more An adaptation of roughness discrimination task successfully used on rats was performed on mice. It was found that mice can master discrimination of rough surfaces using only mystacial vibrissae. This task can be used for studying sensory abilities of genetically modified mice as well as dynamics and pharmacology of complex sensory learning.
Journal of Neuroscience, 2005
Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded t... more Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded trinucleotide (CAG) repeat coding for an extended polyglutamine tract. The disease is inherited in an autosomal dominant manner, with onset of motor, cognitive, and psychiatric symptoms typically occurring in midlife, followed by unremitting progression and eventual death. We report here that motor presymptomatic R6/1 HD mice show a severe impairment of somatosensory-discrimination learning ability in a behavioral task that depends heavily on the barrel cortex. In parallel, there are deficits in barrel-cortex plasticity after a somatosensory whisker-deprivation paradigm. The present study demonstrates deficits in neocortical plasticity correlated with a specific learning impairment involving the same neocortical area, a finding that provides new insight into the cellular basis of early cognitive deficits in HD.
Journal of Neuroscience, 2010
The structure of neurons changes during development and in response to injury or alteration in se... more The structure of neurons changes during development and in response to injury or alteration in sensory experience. Changes occur in the number, shape, and dimensions of dendritic spines together with their synapses. However, precise data on these changes in response to learning are sparse. Here, we show using quantitative transmission electron microscopy that a simple form of learning involving mystacial vibrissae results in ϳ70% increase in the density of inhibitory synapses on spines of neurons located in layer IV barrels that represent the stimulated vibrissae. The spines contain one asymmetrical (excitatory) and one symmetrical (inhibitory) synapse (double-synapse spines), and their density increases threefold as a result of learning with no apparent change in the density of asymmetrical synapses. This effect seems to be specific for learning because pseudoconditioning (in which the conditioned and unconditioned stimuli are delivered at random) does not lead to the enhancement of symmetrical synapses but instead results in an upregulation of asymmetrical synapses on spines. Symmetrical synapses of cells located in barrels receiving the conditioned stimulus also show a greater concentration of GABA in their presynaptic terminals. These results indicate that the immediate effect of classical conditioning in the "conditioned" barrels is rapid, pronounced, and inhibitory.
Neuroscience, 2013
The maintenance of neural circuit stability is a dynamic process that requires the plasticity of ... more The maintenance of neural circuit stability is a dynamic process that requires the plasticity of many cellular and synaptic components. By changing the excitatory/inhibitory balance, inhibitory GABAergic plasticity can regulate excitability, and contribute to neural circuit function and refinement in learning and memory. Increased inhibitory GABAergic neurotransmission has been shown in brain structures involved in the learning process. Previously, we showed that classical conditioning in which tactile stimulation of one row of vibrissae (conditioned stimulus, CS) was paired with a tail shock (unconditioned stimulus, UCS) in adult mice results in the increased density of GABAergic interneurons and increased expression of glutamic acid decarboxylase (GAD)-67 in barrels of the ''trained'' row cortical representation. In inhibitory neurons of the rat cortex GAD co-localizes with several proteins and peptides. We found previously that the density of the parvalbumin (GAD+/Prv+)-containing subpopulation is not changed after conditioning. In the present study, we examined GAB-Aergic somatostatin (Som)-, calbindin (CB)-and calretinin (CR)-positive interneurons in the cortical representation of ''trained'' vibrissae after training. Cells showing double immunostaining for GAD/Som, GAD/CR and GAD/CB were counted in the barrels representing vibrissae activated during the training and in control, untouched rows. We found a substantial increase of GAD/Som-containing cells in the trained row representation. No changes in the density of GAD/CR or GAD/CB neurons were observed. These results suggest that Som-containing interneurons are involved in learning-induced changes in the inhibitory cortical network.
Neurobiology of Disease, 2004
Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropatho... more Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropathology in HD is a selective neuronal cell death in several brain regions including cortex. Although changes in synaptic plasticity were shown within the hippocampus and striatum of HD transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in HD. We examined the impact of the HD transgene upon learning-dependent plasticity of cortical representational maps. The effect of associative learning, in which stimulation of a row of vibrissae was paired with appetitive stimulus, upon functional representations of vibrissae in the barrel cortex, was investigated with 2-deoxyglucose brain mapping in presymptomatic R6/1 HD mice. In wild-type mice, cortical representation of the row of vibrissae involved in the training was expanded, while in HD mice the representation of this row was not expanded. The results suggest that presymptomatic R6/1 HD transgenic mice show deficits in plasticity of primary somatosensory cortex. D 2004 Elsevier Inc. All rights reserved.
Experimental Brain Research, 2011
This study addressed the paradoxical observation that movement is essential for tactile explorati... more This study addressed the paradoxical observation that movement is essential for tactile exploration, and yet is accompanied by movement-related gating or suppression of tactile detection. Knowing that tactile gating covaries with the speed of movement (faster movements, more gating), we hypothesized that there would be no tactile gating at slower speeds of movement, corresponding to speeds commonly used during tactile exploration (<200 mm/s). Subjects (n = 21) detected the presence or absence of a weak electrical stimulus applied to the skin of the right middle Wnger during two conditions: rest and active elbow extension. Movement speed was systematically varied from 50 to »1,000 mm/s. No subject showed evidence of tactile gating at the slowest speed tested, 50 mm/s (rest versus movement), but all subjects showed decreased detection at one or more higher speeds. For each subject, we calculated the critical speed, corresponding to the speed at which detection fell to 0.5 (chance). The mean critical speed was 472 mm/s and >200 mm/s in almost all subjects (19/21). This result is consistent with our hypothesis that subjects optimize the speed of movement during tactile exploration to avoid speeds associated with tactile gating. This strategy thus maximizes the quality of the tactile feedback generated during tactile search and improves perception.
European Journal of Neuroscience, 2004
The effect of the extracellular matrix recognition molecule tenascin-C on cerebral plasticity ind... more The effect of the extracellular matrix recognition molecule tenascin-C on cerebral plasticity induced by vibrissectomy was investigated with 2-deoxyglucose (2DG) brain mapping in tenascin-C-deficient mice. Unilateral vibrissectomy sparing row C of vibrissae was performed in young adult mice. Two months later, cortical representations of spared row C vibrissae and control row C on the other side of the snout were visualized by [(14)C]2DG autoradiography. In both wild-type and tenascin-C-deficient mice, cortical representation of the spared row was expanded in all layers of the barrel cortex. However, the effect was significantly more extensive in wild-type animals than in the mutant. Elimination of tenascin-C by genetic manipulation thus reduces the effect of vibrissectomy observed in the somatosensory cortex. No increase in number of fibres in the vibrissal nerve of spared vibrissae was seen, and occurrence of additional nerve to the spared follicle was very rare. Thus, in tenascin-C-deficient mice functional plasticity seems to be impaired within the CNS.
European Journal of Neuroscience, 2011
ABSTRACT Matrix metalloproteinases (MMPs) are fine modulators of brain plasticity and pathophysio... more ABSTRACT Matrix metalloproteinases (MMPs) are fine modulators of brain plasticity and pathophysiology. The inhibition of MMPs shortly after ischaemic stroke reduces the infarct size and has beneficial effects on post-stroke behavioural recovery. Our previous studies have shown that photothrombotic cortical stroke disrupts use-dependent plasticity in the neighbouring cortex. The aim of the present study was to check whether the inhibition of MMPs after photothrombosis rescued the plastic capacity of the barrel cortex. To induce plasticity in adult mice, a unilateral deprivation of all vibrissae except row C was applied. The deprivation started immediately after stroke and lasted 7 days. This procedure, in control (non-stroke) animals, results in an enlargement of functional representation of the spared row, as shown with [(14)C]2-deoxyglucose uptake mapping. In mice with stroke induced by photothrombosis in the vicinity of the barrel cortex, vibrissae deprivation did not result in an enlargement of the cortical representation of the spared row C of vibrissae, which confirmed our previous results. However, when mice were injected with the broad-spectrum inhibitor of MMPs FN-439 (10 mg/kg, i.v.) immediately before a stroke, an enlargement of the representation of the spared row similar to the enlargement found in sham mice was observed. These results indicate the involvement of MMPs in the impairment of use-dependent plasticity in the vicinity of an ischaemic lesion.
European Journal of Neuroscience, 2006
In the somatosensory system, inputs from one side of the body are only transmitted to the contral... more In the somatosensory system, inputs from one side of the body are only transmitted to the contralateral primary somatosensory cortex, but both sides of the body representation can interact via interhemispheric connections. These interactions depend on the behavioural requirements of the animal and its level of arousal. During the process of learning, alertness and attention may modify the responsiveness of neuronal pathways. We functionally mapped the brains of mice by using [ 14 C]2-deoxyglucose (2DG) autoradiography during the first and the third session of a classical conditioning paradigm, involving whiskers stimulation on one side of the muzzle paired with an aversive or appetitive unconditioned stimulus. During the first pairing session, an increased 2DG uptake was seen in the barrel cortex of both hemispheres, independently of the type of applied unconditioned stimulus. In the third session of the sensory pairing, activation of the barrel cortex was solely contralateral, as expected after unilateral whisker stimulation. Thus, sensory stimulation directed to one cerebral hemisphere during the initial stages of Pavlovian conditioning activates the primary sensory area in both hemispheres. These results suggest that during the early phase of conditioning, when alertness is presumably strongest, the interhemispheric interactions are enhanced.
Behavioural Brain Research, 2013
h i g h l i g h t s • We studied cross-correlations among the elements of the thalamocortical loop.
Behavioural Brain Research, 2009
The neural bases of appetitive and aversive conditioning are different, and at various stages of ... more The neural bases of appetitive and aversive conditioning are different, and at various stages of learning, may engage distinct cortical and subcortical networks. Using [ 14 C]2-deoxyglucose (2-DG) autoradiography, we examined brain activation in mice during the first and the third sessions of a classical conditioning involving stimulation of whiskers on one side of the muzzle (conditioned stimulus, CS) paired with an aversive or appetitive unconditioned stimulus (UCS). The nucleus basalis magnocellularis showed stronger labelling during appetitive conditioning while the lateral hypothalamus was activated only during aversive pairing session. Also, in the appetitive training (both conditioning and pseudoconditioning), the ventral pallidum responded differently than in the aversive situation. A tendency for higher labelling of basolateral amygdala was noted in aversive conditioning. Somatosensory thalamic nuclei, as well as posterior parietal cortex and nucleus accumbens core, were strongly activated in both conditions during the first training session, but only by appetitive conditioning during the third session. With the exception of the nucleus basalis, ventral pallidum and lateral hypothalamus, appetitive or aversive classical conditioning increased 2-DG uptake in a similar set of brain structures. Activation of nucleus accumbens core, posterior parietal cortex, and structures of the somatosensory pathway decreases with the duration of training presumably due to different involvement of attention and different dynamics of the two variants of conditioning.
Behavioural brain …, Jan 1, 2010
The cingulate cortex, which comprises of two major subdivisions -anterior cingulate cortex (CG) a... more The cingulate cortex, which comprises of two major subdivisions -anterior cingulate cortex (CG) and retrosplenial cortex (RSP), is implicated in many cognitive functions. The RSP is an important node in the systemic integration network. Studies point to its role in learning that involves spatial stimuli and navigation. Relatively little is known about its involvement in simple learning such as classical conditioning. We examined the involvement of the two cytoarchitectonic divisions, agranular and granular, of the rostral and caudal RSP in a delay conditioning, where stimulation of the facial vibrissae was paired with a tail shock. During the conditioning session the [ 14 C]-2-deoxyglucose (2DG) brain mapping was performed. Effectiveness of conditioning was assessed with frequency of head movements, which decreased in the course of the conditioning. 2DG uptake in RSP and additionally in CG was examined in conditioned, pseudoconditioned and stimulated control groups. The metabolic labeling was elevated in caudal and rostral both RSP and CG in the conditioned group, but not in animals which received CS or UCS alone. Comparison between conditioned and pseudoconditioned groups showed the specific activation by associative learning in both divisions of the rostral RSP and rostral CG. Counts of c-Fos expressing nuclei confirmed activation of the rostral RSP in the CS + UCS group. These data support the concept of RSP as structure that, besides its recognized role in visuospatial learning, monitors and reacts to activity of brain systems responsible for other types of learning and, together with CG, subserve cognitive processes, with simple associative learning among them.
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Papers by Anita Cybulska-Klosowicz