bioRxiv (Cold Spring Harbor Laboratory), Dec 11, 2022
Recent progress in cortical stem cell transplantation has demonstrated its potential to repair th... more Recent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types within the grafts, abnormal proportions of cell types, abnormal cytoarchitecture, and inefficient vascularization. Here, we devised a transplant platform for testing neocortical tissue prototypes. Dissociated mouse embryonic telencephalic cells in a liquid scaffold were transplanted into aspiration-lesioned adult mouse cortices. The donor neuronal precursors differentiated into upper and deep layer neurons that exhibited synaptic puncta, projected outside of the graft to appropriate brain areas, became electrophysiologically active within one month post-transplant, and responded to visual stimuli. Interneurons and oligodendrocytes were present at normal densities in grafts. Grafts became fully vascularized by 1-week posttransplant and vessels in grafts were perfused with blood. With this paradigm, we could also organize cells into layers. Overall, we have provided proof of concept for an in vivo platform that can be used for developing and testing neocortical-like tissue prototypes.
Mentor: Dennis Barbour From the Washington University Undergraduate Research Digest: WUURD, Volum... more Mentor: Dennis Barbour From the Washington University Undergraduate Research Digest: WUURD, Volume 2, Issue 2, Spring 2007. Published by the Office of Undergraduate Research. Henry Biggs, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator, Editor, and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Co-editor
Because of its anatomical connectivity, the entorhinal cortex (EC) in the medial temporal lobe (M... more Because of its anatomical connectivity, the entorhinal cortex (EC) in the medial temporal lobe (MTL) is well-positioned to play a critical role in hippocampal-cortical interaction. Superficial layers of the EC receive processed multisensory information and provide the main cortical input to the hippocampus, while the deep layers of the EC receive output from the hippocampus and provide feedback to other cortical areas (Witter et al., 2000). Owing to this arrangement, the EC may show layerspecific differences in activity related to memory formation and recognition. We examined neuronal activity in the EC of two monkeys performing the Visual Preferential Looking Task (VPLT). Performance on this task reflects recognition memory and is sensitive to the integrity of the hippocampus and adjacent cortical regions (Buffalo et al., 1999; Manns et al., 2000; Zola et al., 2000). Methods Visual preferential looking task (VPLT) For each recording session the monkeys (Macaca mulatta) performed the VPLT, where 200 novel, complex visual images constituted the stimuli of one session. Each image was viewed twice with up to 10 intervening stimuli between presentations. Gaze location was recorded with an infrared eye-tracking system (ISCAN).
Pathological high frequency oscillations (250-600 Hz) are present in the brains of epileptic anim... more Pathological high frequency oscillations (250-600 Hz) are present in the brains of epileptic animals and humans. The etiology of these oscillations and how they contribute to the diseased state remains unclear. This work identifies the presence of microstimulation-evoked high frequency oscillations (250-400 Hz) in dissociated neuronal networks cultured on microelectrode arrays (MEAs). Oscillations are more apparent with higher stimulus voltages. As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away. Oscillations develop across four weeks in vitro. Oscillations still occur in the presence of tetrodotoxin and synaptic blockers, and they cause no apparent disruption in the ability of oscillation-presenting electrodes to elicit directly evoked action potentials (dAPs) or promote the spread of synaptic activity throughout the culture. Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation. Finally, carbenoxolone significantly reduces or eliminates the high frequency oscillations. Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies. This is the first demonstration of stimulus-evoked high frequency oscillations in dissociated cultures. Unlike current models that rely on complex in vivo recording conditions, this work presents a simple controllable model in neuronal cultures on MEAs to further investigate how the oscillations occur at the molecular level and how they may contribute to the pathophysiology of disease.
Proceedings of the National Academy of Sciences, 2015
Significance Characterizing the dynamic encoding of body orientation and eye movements in the bra... more Significance Characterizing the dynamic encoding of body orientation and eye movements in the brain is central to understanding spatial representation. Studies in rodents have revealed an allocentric heading representation system known as the head-direction network. Visual information is presumed to be critical to rodent head-direction encoding; however, differences in the primate and rodent visual systems along with differences in exploratory behaviors across species have made it difficult to directly extend the findings from rodents to primates. This study describes a previously unidentified functional cell type in the primate entorhinal cortex that shows selectivity for the direction of saccadic eye movements. Future research avenues critical to increasing our understanding of spatial representation in the brain are suggested.
Because of its anatomical connectivity, the entorhinal cortex (EC) in the medial temporal lobe (M... more Because of its anatomical connectivity, the entorhinal cortex (EC) in the medial temporal lobe (MTL) is well-positioned to play a critical role in hippocampal-cortical interaction. Superficial layers of the EC receive processed multisensory information and provide the main cortical input to the hippocampus, while the deep layers of the EC receive output from the hippocampus and provide feedback to other cortical areas (Witter et al., 2000). Owing to this arrangement, the EC may show layer-specific differences in activity related to memory formation and recognition. We examined neural activity in the EC in a monkey performing the Visual Paired Comparison (VPC) task. Performance on this task represents recognition memory and is sensitive to the integrity of the hippocampus and adjacent cortical regions (Buffalo et al., 1999; Manns et al., 2000; Zola et al., 2000). 1. Behavioral performance Across 20 test sessions, the monkey demonstrated a significant preference for novelty. On average, he spent about two-thirds of the test phase looking at the novel image (mean 64 % +/- 15%; p < 0.001, t-test). percentage of trials
We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory c... more We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast v...
We recently demonstrated that position in visual space is represented by grid cells in the primat... more We recently demonstrated that position in visual space is represented by grid cells in the primate entorhinal cortex (EC), suggesting that visual exploration of complex scenes in primates may employ signaling mechanisms similar to those used during exploration of physical space via movement in rodents. Here, we describe a group of saccade direction (SD) cells that encode eye movement information in the monkey EC during free-viewing of complex images. Significant saccade direction encoding was found in 20% of the cells recorded in the posterior EC. SD cells were generally broadly tuned and two largely separate populations of SD cells encoded future and previous saccade direction. Some properties of these cells resemble those of head-direction cells in rodent EC, suggesting that the same neural circuitry may be capable of performing homologous spatial computations under different exploratory contexts.
vision spatial representation medial temporal lobe head direction grid cell
Pathological high frequency oscillations (250–600 Hz) are present in the brains of epileptic anim... more Pathological high frequency oscillations (250–600 Hz) are present in the brains of epileptic animals and humans. The etiology of these oscillations and how they contribute to the diseased state remains unclear. This work identifies the presence of microstimulation-evoked high frequency oscillations (250–400 Hz) in dissociated neuronal networks cultured on microelectrode arrays (MEAs). Oscillations are more apparent with higher stimulus voltages. As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away. Oscillations develop across four weeks in vitro. Oscillations still occur in the presence of tetrodotoxin and synaptic blockers, and they cause no apparent disruption in the ability of oscillation-presenting electrodes to elicit directly evoked action potentials (dAPs) or promote the spread of synaptic activity throughout the culture. Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation. Finally, carbenoxolone significantly reduces or eliminates the high frequency oscillations. Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies. This is the first demonstration of stimulus-evoked high frequency oscillations in dissociated cultures. Unlike current models that rely on complex in vivo recording conditions, this work presents a simple controllable model in neuronal cultures on MEAs to further investigate how the oscillations occur at the molecular level and how they may contribute to the pathophysiology of disease.
Place-modulated activity among neurons in the hippocampal formation presents a means to organize ... more Place-modulated activity among neurons in the hippocampal formation presents a means to organize contextual information in the service of memory formation and recall. One particular spatial representation, that of grid cells, has been observed in the entorhinal cortex (EC) of rats and bats, but has yet to be described in single units in primates. Here we examined spatial representations in the EC of head-fixed monkeys performing a free-viewing visual memory task. Individual neurons were identified in the primate EC that emitted action potentials when the monkey fixated multiple discrete locations in the visual field in each of many sequentially presented complex images. These firing fields possessed spatial periodicity similar to a triangular tiling with a corresponding well-defined hexagonal structure in the spatial autocorrelation. Further, these neurons showed theta-band oscillatory activity and changing spatial scale as a function of distance from the rhinal sulcus, which is consistent with previous findings in rodents. These spatial representations may provide a framework to anchor the encoding of stimulus content in a complex visual scene. Together, our results provide a direct demonstration of grid cells in the primate and suggest that EC neurons encode space during visual exploration, even without locomotion.
a b s t r a c t 23 Mapping neuronal responses in the lateral geniculate nucleus (LGN) is key to u... more a b s t r a c t 23 Mapping neuronal responses in the lateral geniculate nucleus (LGN) is key to understanding how visual 24 information is processed in the brain. This paper focuses on our current knowledge of the dynamics the 25 receptive field (RF) as broken down into the classical receptive field (CRF) and the extra-classical 26 receptive field (ECRF) in primate LGN. CRFs in the LGN are known to be similar to those in the retinal gan-27 glion cell layer in terms of both spatial and temporal characteristics, leading to the standard interpreta-28 tion of the LGN as a relay center from retina to primary visual cortex. ECRFs have generally been found to 29 be large and inhibitory, with some differences in magnitude between the magno-, parvo-, and koniocel-30 lular pathways. The specific contributions of the retina, thalamus, and visual cortex to LGN ECRF proper-31 ties are presently unknown. Some reports suggest a retinal origin for extra-classical suppression based on 32 latency arguments and other reports have suggested a thalamic origin for extra-classical suppression. 33 This issue is complicated by the use of anesthetized animals, where cortical activity is likely to be altered. 34 Thus further study of LGN ECRFs is warranted to reconcile these discrepancies. Producing descriptions of 35 RF properties of LGN neurons could be enhanced by employing preferred naturalistic stimuli. Although 36 there has been significant work in cats with natural scene stimuli and noise that statistically imitates nat-37 ural scenes, we highlight a need for similar data from primates. Obtaining these data may be aided by 38 recent advancements in experimental and analytical techniques that permit the efficient study of nonlin-39 ear RF characteristics in addition to traditional linear factors. In light of the reviewed topics, we conclude 40 by suggesting experiments to more clearly elucidate the spatial and temporal structure of ECRFs of pri-41 mate LGN neurons.
Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 µm thick tissue p... more Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 µm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations.
bioRxiv (Cold Spring Harbor Laboratory), Dec 11, 2022
Recent progress in cortical stem cell transplantation has demonstrated its potential to repair th... more Recent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types within the grafts, abnormal proportions of cell types, abnormal cytoarchitecture, and inefficient vascularization. Here, we devised a transplant platform for testing neocortical tissue prototypes. Dissociated mouse embryonic telencephalic cells in a liquid scaffold were transplanted into aspiration-lesioned adult mouse cortices. The donor neuronal precursors differentiated into upper and deep layer neurons that exhibited synaptic puncta, projected outside of the graft to appropriate brain areas, became electrophysiologically active within one month post-transplant, and responded to visual stimuli. Interneurons and oligodendrocytes were present at normal densities in grafts. Grafts became fully vascularized by 1-week posttransplant and vessels in grafts were perfused with blood. With this paradigm, we could also organize cells into layers. Overall, we have provided proof of concept for an in vivo platform that can be used for developing and testing neocortical-like tissue prototypes.
Mentor: Dennis Barbour From the Washington University Undergraduate Research Digest: WUURD, Volum... more Mentor: Dennis Barbour From the Washington University Undergraduate Research Digest: WUURD, Volume 2, Issue 2, Spring 2007. Published by the Office of Undergraduate Research. Henry Biggs, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator, Editor, and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Co-editor
Because of its anatomical connectivity, the entorhinal cortex (EC) in the medial temporal lobe (M... more Because of its anatomical connectivity, the entorhinal cortex (EC) in the medial temporal lobe (MTL) is well-positioned to play a critical role in hippocampal-cortical interaction. Superficial layers of the EC receive processed multisensory information and provide the main cortical input to the hippocampus, while the deep layers of the EC receive output from the hippocampus and provide feedback to other cortical areas (Witter et al., 2000). Owing to this arrangement, the EC may show layerspecific differences in activity related to memory formation and recognition. We examined neuronal activity in the EC of two monkeys performing the Visual Preferential Looking Task (VPLT). Performance on this task reflects recognition memory and is sensitive to the integrity of the hippocampus and adjacent cortical regions (Buffalo et al., 1999; Manns et al., 2000; Zola et al., 2000). Methods Visual preferential looking task (VPLT) For each recording session the monkeys (Macaca mulatta) performed the VPLT, where 200 novel, complex visual images constituted the stimuli of one session. Each image was viewed twice with up to 10 intervening stimuli between presentations. Gaze location was recorded with an infrared eye-tracking system (ISCAN).
Pathological high frequency oscillations (250-600 Hz) are present in the brains of epileptic anim... more Pathological high frequency oscillations (250-600 Hz) are present in the brains of epileptic animals and humans. The etiology of these oscillations and how they contribute to the diseased state remains unclear. This work identifies the presence of microstimulation-evoked high frequency oscillations (250-400 Hz) in dissociated neuronal networks cultured on microelectrode arrays (MEAs). Oscillations are more apparent with higher stimulus voltages. As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away. Oscillations develop across four weeks in vitro. Oscillations still occur in the presence of tetrodotoxin and synaptic blockers, and they cause no apparent disruption in the ability of oscillation-presenting electrodes to elicit directly evoked action potentials (dAPs) or promote the spread of synaptic activity throughout the culture. Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation. Finally, carbenoxolone significantly reduces or eliminates the high frequency oscillations. Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies. This is the first demonstration of stimulus-evoked high frequency oscillations in dissociated cultures. Unlike current models that rely on complex in vivo recording conditions, this work presents a simple controllable model in neuronal cultures on MEAs to further investigate how the oscillations occur at the molecular level and how they may contribute to the pathophysiology of disease.
Proceedings of the National Academy of Sciences, 2015
Significance Characterizing the dynamic encoding of body orientation and eye movements in the bra... more Significance Characterizing the dynamic encoding of body orientation and eye movements in the brain is central to understanding spatial representation. Studies in rodents have revealed an allocentric heading representation system known as the head-direction network. Visual information is presumed to be critical to rodent head-direction encoding; however, differences in the primate and rodent visual systems along with differences in exploratory behaviors across species have made it difficult to directly extend the findings from rodents to primates. This study describes a previously unidentified functional cell type in the primate entorhinal cortex that shows selectivity for the direction of saccadic eye movements. Future research avenues critical to increasing our understanding of spatial representation in the brain are suggested.
Because of its anatomical connectivity, the entorhinal cortex (EC) in the medial temporal lobe (M... more Because of its anatomical connectivity, the entorhinal cortex (EC) in the medial temporal lobe (MTL) is well-positioned to play a critical role in hippocampal-cortical interaction. Superficial layers of the EC receive processed multisensory information and provide the main cortical input to the hippocampus, while the deep layers of the EC receive output from the hippocampus and provide feedback to other cortical areas (Witter et al., 2000). Owing to this arrangement, the EC may show layer-specific differences in activity related to memory formation and recognition. We examined neural activity in the EC in a monkey performing the Visual Paired Comparison (VPC) task. Performance on this task represents recognition memory and is sensitive to the integrity of the hippocampus and adjacent cortical regions (Buffalo et al., 1999; Manns et al., 2000; Zola et al., 2000). 1. Behavioral performance Across 20 test sessions, the monkey demonstrated a significant preference for novelty. On average, he spent about two-thirds of the test phase looking at the novel image (mean 64 % +/- 15%; p < 0.001, t-test). percentage of trials
We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory c... more We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast v...
We recently demonstrated that position in visual space is represented by grid cells in the primat... more We recently demonstrated that position in visual space is represented by grid cells in the primate entorhinal cortex (EC), suggesting that visual exploration of complex scenes in primates may employ signaling mechanisms similar to those used during exploration of physical space via movement in rodents. Here, we describe a group of saccade direction (SD) cells that encode eye movement information in the monkey EC during free-viewing of complex images. Significant saccade direction encoding was found in 20% of the cells recorded in the posterior EC. SD cells were generally broadly tuned and two largely separate populations of SD cells encoded future and previous saccade direction. Some properties of these cells resemble those of head-direction cells in rodent EC, suggesting that the same neural circuitry may be capable of performing homologous spatial computations under different exploratory contexts.
vision spatial representation medial temporal lobe head direction grid cell
Pathological high frequency oscillations (250–600 Hz) are present in the brains of epileptic anim... more Pathological high frequency oscillations (250–600 Hz) are present in the brains of epileptic animals and humans. The etiology of these oscillations and how they contribute to the diseased state remains unclear. This work identifies the presence of microstimulation-evoked high frequency oscillations (250–400 Hz) in dissociated neuronal networks cultured on microelectrode arrays (MEAs). Oscillations are more apparent with higher stimulus voltages. As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away. Oscillations develop across four weeks in vitro. Oscillations still occur in the presence of tetrodotoxin and synaptic blockers, and they cause no apparent disruption in the ability of oscillation-presenting electrodes to elicit directly evoked action potentials (dAPs) or promote the spread of synaptic activity throughout the culture. Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation. Finally, carbenoxolone significantly reduces or eliminates the high frequency oscillations. Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies. This is the first demonstration of stimulus-evoked high frequency oscillations in dissociated cultures. Unlike current models that rely on complex in vivo recording conditions, this work presents a simple controllable model in neuronal cultures on MEAs to further investigate how the oscillations occur at the molecular level and how they may contribute to the pathophysiology of disease.
Place-modulated activity among neurons in the hippocampal formation presents a means to organize ... more Place-modulated activity among neurons in the hippocampal formation presents a means to organize contextual information in the service of memory formation and recall. One particular spatial representation, that of grid cells, has been observed in the entorhinal cortex (EC) of rats and bats, but has yet to be described in single units in primates. Here we examined spatial representations in the EC of head-fixed monkeys performing a free-viewing visual memory task. Individual neurons were identified in the primate EC that emitted action potentials when the monkey fixated multiple discrete locations in the visual field in each of many sequentially presented complex images. These firing fields possessed spatial periodicity similar to a triangular tiling with a corresponding well-defined hexagonal structure in the spatial autocorrelation. Further, these neurons showed theta-band oscillatory activity and changing spatial scale as a function of distance from the rhinal sulcus, which is consistent with previous findings in rodents. These spatial representations may provide a framework to anchor the encoding of stimulus content in a complex visual scene. Together, our results provide a direct demonstration of grid cells in the primate and suggest that EC neurons encode space during visual exploration, even without locomotion.
a b s t r a c t 23 Mapping neuronal responses in the lateral geniculate nucleus (LGN) is key to u... more a b s t r a c t 23 Mapping neuronal responses in the lateral geniculate nucleus (LGN) is key to understanding how visual 24 information is processed in the brain. This paper focuses on our current knowledge of the dynamics the 25 receptive field (RF) as broken down into the classical receptive field (CRF) and the extra-classical 26 receptive field (ECRF) in primate LGN. CRFs in the LGN are known to be similar to those in the retinal gan-27 glion cell layer in terms of both spatial and temporal characteristics, leading to the standard interpreta-28 tion of the LGN as a relay center from retina to primary visual cortex. ECRFs have generally been found to 29 be large and inhibitory, with some differences in magnitude between the magno-, parvo-, and koniocel-30 lular pathways. The specific contributions of the retina, thalamus, and visual cortex to LGN ECRF proper-31 ties are presently unknown. Some reports suggest a retinal origin for extra-classical suppression based on 32 latency arguments and other reports have suggested a thalamic origin for extra-classical suppression. 33 This issue is complicated by the use of anesthetized animals, where cortical activity is likely to be altered. 34 Thus further study of LGN ECRFs is warranted to reconcile these discrepancies. Producing descriptions of 35 RF properties of LGN neurons could be enhanced by employing preferred naturalistic stimuli. Although 36 there has been significant work in cats with natural scene stimuli and noise that statistically imitates nat-37 ural scenes, we highlight a need for similar data from primates. Obtaining these data may be aided by 38 recent advancements in experimental and analytical techniques that permit the efficient study of nonlin-39 ear RF characteristics in addition to traditional linear factors. In light of the reviewed topics, we conclude 40 by suggesting experiments to more clearly elucidate the spatial and temporal structure of ECRFs of pri-41 mate LGN neurons.
Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 µm thick tissue p... more Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 µm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations.
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Papers by Nathan Killian
vision spatial representation medial temporal lobe head direction grid cell
vision spatial representation medial temporal lobe head direction grid cell