Characterization of interregional interactions in brain is essential for understanding the mechan... more Characterization of interregional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (μ)-electrocorticography (μECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped μECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current μECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheetshaped 64-channel μECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the μECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the μECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our μECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.
During the execution of working memory tasks, task-relevant information is processed by local cir... more During the execution of working memory tasks, task-relevant information is processed by local circuits across multiple brain regions. How this multi-area computation is conducted by the brain remains largely unknown. To explore such mechanisms in spatial working memory, we constructed a neural network model involving parvalbumin-positive, somatostatin-positive and vasoactive intestinal polypeptidepositive interneurons in the hippocampal CA1 and the superficial and deep layers of medial entorhinal cortex (MEC). Our model is based on a hypothesis that cholinergic modulations differently regulate information flows across CA1 and MEC at memory encoding, maintenance and recall during delayed nonmatching-to-place tasks. In the model, theta oscillation coordinates the proper timing of interactions between these regions. Furthermore, the model predicts that MEC is engaged in decoding as well as encoding spatial memory, which we confirmed by experimental data analysis. Thus, our model accounts for the neurobiological characteristics of the cross-area information routing underlying working memory tasks.
epidermogenesis and inhibit neurogenesis (Wilson and Hemmati-Brivanlou, 1995; Sasai et al., 1995)... more epidermogenesis and inhibit neurogenesis (Wilson and Hemmati-Brivanlou, 1995; Sasai et al., 1995). Noggin, Follistatin, and Chd bind directly to BMP4-class molecules in the extracellular space and trap BMP into an inactive complex (Piccolo et al., 1996; Zimmerman et
Proceedings of the National Academy of Sciences of the United States of America, Aug 2, 2005
We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3 ؉ rost... more We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3 ؉ rostral brain progenitors are generated by culturing ES cells under serum-free suspension conditions (SFEB culture) in the presence of Wnt and Nodal antagonists (Dkk1 and LeftyA), and subsequently steered to differentiate into Rx ؉ cells (16%) by treatment with activin and serum. Consistent with the characteristics of early neural retinal precursors, the induced Rx ؉ cells coexpress Pax6 and the mitotic marker Ki67, but not Nestin. The ES cell-derived precursors efficiently generate cells with the photoreceptor phenotype (rhodopsin ؉ , recoverin ؉) when cocultured with embryonic retinal cells. Furthermore, organotypic culture studies demonstrate the selective integration and survival of ES cell-derived cells with the photoreceptor phenotype (marker expression and morphology) in the outer nuclear layer of the retina. Taken together, ES cells treated with SFEB͞Dkk1͞LeftyA͞ serum͞activin generate neural retinal precursors, which have the competence of photoreceptor differentiation. regenerative medicine ͉ differentiation ͉ photoreceptor ͉ induction ͉ Six3
bioRxiv (Cold Spring Harbor Laboratory), Feb 4, 2021
Neuronal ensembles in the amygdala, ventral hippocampus, and prefrontal cortex are involved in fe... more Neuronal ensembles in the amygdala, ventral hippocampus, and prefrontal cortex are involved in fear memory; however, how the interregional ensemble interactions support memory remains elusive. Using multi-regional large-scale electrophysiology in the aforementioned structures of fear-conditioned rats, we demonstrated that local ensembles activated during fear memory acquisition were interregionally coactivated during subsequent sleep, which relied on brief bouts of fast network oscillations. During memory retrieval, coactivations reappeared, accompanying fast oscillations. Ensembles contributing to interregional coactivation were configured prior to memory acquisition in the amygdala and prefrontal cortex but developed through experience in the hippocampus. Our observation suggests that elements of a given memory are instantly encoded within various brain regions in a pre-configured manner, whereas hippocampal ensembles and the network for interregional integration of the distributed information develop in an experience-dependent manner to form a new memory, which is consistent with hippocampal memory index hypothesis.
State-of-the-art techniques allow researchers to record large numbers of spike trains in parallel... more State-of-the-art techniques allow researchers to record large numbers of spike trains in parallel for many hours. With enough such data, we should be able to infer the connectivity among neurons. Here we develop a method for reconstructing neuronal circuitry by applying a generalized linear model (GLM) to spike cross-correlations. Our method estimates connections between neurons in units of postsynaptic potentials and the amount of spike recordings needed to verify connections. The performance of inference is optimized by counting the estimation errors using synthetic data. This method is superior to other established methods in correctly estimating connectivity. By applying our method to rat hippocampal data, we show that the types of estimated connections match the results inferred from other physiological cues. Thus our method provides the means to build a circuit diagram from recorded spike trains, thereby providing a basis for elucidating the differences in information processing in different brain regions.
From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expr... more From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expressed in neural tissues and sensory epithelia. In this report, we show that Sox2 function is required for neural differentiation of early Xenopus ectoderm. Microinjection of dominantnegative forms of Sox2 (dnSox2) mRNA inhibits neural differentiation of animal caps caused by attenuation of BMP signals. Expression of dnSox2 in developing embryos suppresses expression of N-CAM and regional neural markers. We have analyzed temporal requirement of Sox2mediated signaling by using an inducible dnSox2 construct fused to the ligand-binding domain of the glucocorticoid receptor. Attenuation of Sox2 function both from the late blastula stage and from the late gastrula stage onwards causes an inhibition of neural differentiation in animal caps and in whole embryos. Additionally, dnSox2-injected cells that fail to differentiate into neural tissues are not able to adopt epidermal cell fate. These data suggest that Sox2class genes are essential for early neuroectoderm cells to consolidate their neural identity during secondary steps of neural differentiation.
Monosynaptic connection from the subiculum to medial mammillary nucleus neurons projecting to the anterior thalamus and Gudden’s ventral tegmental nucleus
Neuroscience Research, Oct 1, 2021
As a major hippocampal output structure, the subiculum projects to diverse cortical and subcortic... more As a major hippocampal output structure, the subiculum projects to diverse cortical and subcortical areas, and its projection to the medial mammillary nucleus (MM) has been implicated in memory. Major efferent targets of the MM are the anteroventral and anteromedial thalamic nuclei and Gudden's ventral tegmental nucleus. These projections may play a key role in distributing subicular information. However, it remains unknown whether neurons in the MM that receive monosynaptic input from the subiculum project to these target regions. We addressed this issue with anterograde transsynaptic tracing mediated using adeno-associated virus serotype 1 (AAV1). Injection of AAV1-Cre and a Cre-dependent AAV encoding enhanced yellow fluorescent protein (EYFP) into the rat dorsal subiculum and MM, respectively, labeled the soma of the MM and axons in the anteroventral / anteromedial thalamic nuclei and Gudden's ventral tegmental nucleus with EYFP. The EYFP-positive neurons in the MM were immunoreactive for glutamate and leu-enkephalin and received perisomatic GABAergic inputs. These results revealed monosynaptic projections from the subiculum to MM neurons projecting to the anteroventral / anteromedial thalamic nuclei and Gudden's ventral tegmental nucleus. This monosynaptic connection may support a fast and robust signal flow through the hippocampal-mammillothalamic and hippocampal-mammillotegmental pathways.
bioRxiv (Cold Spring Harbor Laboratory), Oct 4, 2022
Characterization of interregional interactions in brain is essential for understanding the mechan... more Characterization of interregional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro ()-electrocorticography (ECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped ECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current ECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel ECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the ECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the ECoG device reached to the most ventral part of cerebral preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
following. First, LFP trace during REM epochs were band-pass filtered (5-12 Hz), yielding y(t). A... more following. First, LFP trace during REM epochs were band-pass filtered (5-12 Hz), yielding y(t). Amplitude of theta oscillations were derived from Hilbert transform of y(t), and peaks of theta oscillations were detected as the positive to negative zero crossings of the derivative dy/dt. Inter-peak intervals were smoothed using an eleven-sample rectangular kernel. Candidate epochs were detected if smoothed inter-peak intervals were shorter than 10 percentile of smoothed inter-peak intervals. The candidate epochs were identified as phasic REM epochs if the following criteria were all fulfilled. (1) Duration of an epoch was longer than 900 msec. (2) Minimum of smoothed inter-peak intervals during an epoch was shorter than 5 percentile of smoothed inter-spike intervals. (3) Mean amplitude of theta oscillations during an epoch was larger than mean amplitude of theta oscillations during the entire REM sleep. A total of 5844 sec (3.68 % of REM sleep episodes) was identified as phasic REM ep...
In the present study we provide the first systematic and quantitative hodological study of the ca... more In the present study we provide the first systematic and quantitative hodological study of the calbindin-expressing (CB+) principal neurons in layer II of the entorhinal cortex and compared the respective projections of the lateral and medial subdivisions of the entorhinal cortex. Using elaborate quantitative retrograde tracing, complemented by anterograde tracing, we report that the layer II CB+ population comprises neurons with diverse, mainly excitatory projections. At least half of them originate local intrinsic and commissural projections which distribute mainly to layer I and II. We further show that long-range CB+ projections from the two entorhinal subdivisions differ substantially in that MEC projections mainly target field CA1 of the hippocampus, whereas LEC CB+ projections distribute much more widely to a substantial number of known forebrain targets. This connectional difference between the CB+ populations in LEC and MEC is reminiscent of the overall projection pattern of the two entorhinal subdivisions.
Acquisition of Auditory Discrimination Mediated by Different Processes through Two Distinct Circuits Linked to the Lateral Striatum
The striatum, the central hub of cortico-basal ganglia loops, contains functionally heterogeneous... more The striatum, the central hub of cortico-basal ganglia loops, contains functionally heterogeneous subregions distinguished by the topographic patterns of structural connectivity. These subregions mediate various processes of procedural learning. However, it remains unclear when and how striatal subregions engage in a new learning of sensory stimulus-based decision-making. Here, we show that the anterior dorsolateral striatum (aDLS) and posterior ventrolateral striatum (pVLS) are activated in a different temporal pattern during the acquisition phase of auditory discrimination learning. The aDLS promotes the behavioral strategy by the stimulus-response association while suppressing those driven by the response-outcome association, and the pVLS is involved in forming and maintaining the stimulus-response strategy. These two subregions exhibit distinct event-related neuronal responses during the learning processes. Our findings demonstrate that aDLS and pVLS neurons integrate the new le...
Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2020
The hippocampus processes multimodal information, including place, time, speed, reward, and memor... more The hippocampus processes multimodal information, including place, time, speed, reward, and memory. However, how such information is distributed to multiple downstream areas remains poorly understood. The subiculum is the major hippocampal output structure that receives the hippocampal CA1 output and projects to multiple cortical/subcortical areas. Despite its anatomical importance, the nature of information distribution from the subiculum is unknown. We investigated this issue by optogenetically identifying the projection targets of subicular neurons during large-scale extracellular recordings in freely behaving rats. We introduced channelrhodopsin-2 and a 256-channel silicon probe into the subiculum, and implanted four optical fibers above subicular projection targets. Then, axonal projections of the recorded subicular neurons were determined by detecting antidromic spikes generated by blue-light irradiation to the projection targets. During multiple behavioral tasks and sleep, the subicular projection neurons were entrained to neural oscillations differentially and conveyed distinct information depending on the projection targets. These results suggest the prominent role of the subiculum in distributing hippocampal information to multiple downstream targets in a pathway-specific manner.
Synthetic spike data generated by a network of 1,000 Hodgkin-Huxley type neurons
This is the dataset used for evaluating the performance of the methods for estimating synaptic co... more This is the dataset used for evaluating the performance of the methods for estimating synaptic connectivity from multiple spike trains (Kobayashi et al., 2018 BioRxiv). See README file about the data format and the paper about the simulation procedure.<br>
architectonics and connectivity patterns (MacLean, 1990). However, the physiological mechanisms t... more architectonics and connectivity patterns (MacLean, 1990). However, the physiological mechanisms that allow segregation and integration of neuronal informa-tion in the highly interconnected cortical-hippocampal networks (Sporns et al., 2000) are poorly understood. and Borbely, 1997; Battaglia et al., 2004) as unique temporal windows to examine how neocortical, paleo-cortical (parahippocampal), and hippocampal networks integrate and segregate the activity of their neurons without the disadvantage of surgical or pharmacological manipulations. Do synchronous neocortical patterns associated with slow oscillations invade and affect all parahippocampal and hippocampal subregions equally
CA3 circuit model compressing sequential information in theta oscillation and replay
The hippocampus compresses the sequential information in a theta oscillation cycle and short-term... more The hippocampus compresses the sequential information in a theta oscillation cycle and short-term sequential activities during sharp-wave ripple while sleeping or resting; these processes are known as theta sequence and replay, respectively. The theta sequence is based on theta phase precession patterns of individual neurons. However, how these sequential neuronal activities are generated and how they store information about the outside environment remains unknown. We developed a hippocampal cornu ammonis (CA)3 computational model based on the biological CA3 circuit’s anatomical and electrophysiological evidence to address these. The model comprises theta rhythm inhibition, place input, and CA3-CA3 plastic recurrent connection. The model could compress the sequence of the external inputs and reproduce theta phase precession and replay, learn additional sequences, and reorganize previously learned sequences. A gradual increase in synaptic inputs, controlled by interactions between th...
Characterization of interregional interactions in brain is essential for understanding the mechan... more Characterization of interregional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (μ)-electrocorticography (μECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped μECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current μECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheetshaped 64-channel μECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the μECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the μECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our μECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.
During the execution of working memory tasks, task-relevant information is processed by local cir... more During the execution of working memory tasks, task-relevant information is processed by local circuits across multiple brain regions. How this multi-area computation is conducted by the brain remains largely unknown. To explore such mechanisms in spatial working memory, we constructed a neural network model involving parvalbumin-positive, somatostatin-positive and vasoactive intestinal polypeptidepositive interneurons in the hippocampal CA1 and the superficial and deep layers of medial entorhinal cortex (MEC). Our model is based on a hypothesis that cholinergic modulations differently regulate information flows across CA1 and MEC at memory encoding, maintenance and recall during delayed nonmatching-to-place tasks. In the model, theta oscillation coordinates the proper timing of interactions between these regions. Furthermore, the model predicts that MEC is engaged in decoding as well as encoding spatial memory, which we confirmed by experimental data analysis. Thus, our model accounts for the neurobiological characteristics of the cross-area information routing underlying working memory tasks.
epidermogenesis and inhibit neurogenesis (Wilson and Hemmati-Brivanlou, 1995; Sasai et al., 1995)... more epidermogenesis and inhibit neurogenesis (Wilson and Hemmati-Brivanlou, 1995; Sasai et al., 1995). Noggin, Follistatin, and Chd bind directly to BMP4-class molecules in the extracellular space and trap BMP into an inactive complex (Piccolo et al., 1996; Zimmerman et
Proceedings of the National Academy of Sciences of the United States of America, Aug 2, 2005
We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3 ؉ rost... more We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3 ؉ rostral brain progenitors are generated by culturing ES cells under serum-free suspension conditions (SFEB culture) in the presence of Wnt and Nodal antagonists (Dkk1 and LeftyA), and subsequently steered to differentiate into Rx ؉ cells (16%) by treatment with activin and serum. Consistent with the characteristics of early neural retinal precursors, the induced Rx ؉ cells coexpress Pax6 and the mitotic marker Ki67, but not Nestin. The ES cell-derived precursors efficiently generate cells with the photoreceptor phenotype (rhodopsin ؉ , recoverin ؉) when cocultured with embryonic retinal cells. Furthermore, organotypic culture studies demonstrate the selective integration and survival of ES cell-derived cells with the photoreceptor phenotype (marker expression and morphology) in the outer nuclear layer of the retina. Taken together, ES cells treated with SFEB͞Dkk1͞LeftyA͞ serum͞activin generate neural retinal precursors, which have the competence of photoreceptor differentiation. regenerative medicine ͉ differentiation ͉ photoreceptor ͉ induction ͉ Six3
bioRxiv (Cold Spring Harbor Laboratory), Feb 4, 2021
Neuronal ensembles in the amygdala, ventral hippocampus, and prefrontal cortex are involved in fe... more Neuronal ensembles in the amygdala, ventral hippocampus, and prefrontal cortex are involved in fear memory; however, how the interregional ensemble interactions support memory remains elusive. Using multi-regional large-scale electrophysiology in the aforementioned structures of fear-conditioned rats, we demonstrated that local ensembles activated during fear memory acquisition were interregionally coactivated during subsequent sleep, which relied on brief bouts of fast network oscillations. During memory retrieval, coactivations reappeared, accompanying fast oscillations. Ensembles contributing to interregional coactivation were configured prior to memory acquisition in the amygdala and prefrontal cortex but developed through experience in the hippocampus. Our observation suggests that elements of a given memory are instantly encoded within various brain regions in a pre-configured manner, whereas hippocampal ensembles and the network for interregional integration of the distributed information develop in an experience-dependent manner to form a new memory, which is consistent with hippocampal memory index hypothesis.
State-of-the-art techniques allow researchers to record large numbers of spike trains in parallel... more State-of-the-art techniques allow researchers to record large numbers of spike trains in parallel for many hours. With enough such data, we should be able to infer the connectivity among neurons. Here we develop a method for reconstructing neuronal circuitry by applying a generalized linear model (GLM) to spike cross-correlations. Our method estimates connections between neurons in units of postsynaptic potentials and the amount of spike recordings needed to verify connections. The performance of inference is optimized by counting the estimation errors using synthetic data. This method is superior to other established methods in correctly estimating connectivity. By applying our method to rat hippocampal data, we show that the types of estimated connections match the results inferred from other physiological cues. Thus our method provides the means to build a circuit diagram from recorded spike trains, thereby providing a basis for elucidating the differences in information processing in different brain regions.
From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expr... more From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expressed in neural tissues and sensory epithelia. In this report, we show that Sox2 function is required for neural differentiation of early Xenopus ectoderm. Microinjection of dominantnegative forms of Sox2 (dnSox2) mRNA inhibits neural differentiation of animal caps caused by attenuation of BMP signals. Expression of dnSox2 in developing embryos suppresses expression of N-CAM and regional neural markers. We have analyzed temporal requirement of Sox2mediated signaling by using an inducible dnSox2 construct fused to the ligand-binding domain of the glucocorticoid receptor. Attenuation of Sox2 function both from the late blastula stage and from the late gastrula stage onwards causes an inhibition of neural differentiation in animal caps and in whole embryos. Additionally, dnSox2-injected cells that fail to differentiate into neural tissues are not able to adopt epidermal cell fate. These data suggest that Sox2class genes are essential for early neuroectoderm cells to consolidate their neural identity during secondary steps of neural differentiation.
Monosynaptic connection from the subiculum to medial mammillary nucleus neurons projecting to the anterior thalamus and Gudden’s ventral tegmental nucleus
Neuroscience Research, Oct 1, 2021
As a major hippocampal output structure, the subiculum projects to diverse cortical and subcortic... more As a major hippocampal output structure, the subiculum projects to diverse cortical and subcortical areas, and its projection to the medial mammillary nucleus (MM) has been implicated in memory. Major efferent targets of the MM are the anteroventral and anteromedial thalamic nuclei and Gudden's ventral tegmental nucleus. These projections may play a key role in distributing subicular information. However, it remains unknown whether neurons in the MM that receive monosynaptic input from the subiculum project to these target regions. We addressed this issue with anterograde transsynaptic tracing mediated using adeno-associated virus serotype 1 (AAV1). Injection of AAV1-Cre and a Cre-dependent AAV encoding enhanced yellow fluorescent protein (EYFP) into the rat dorsal subiculum and MM, respectively, labeled the soma of the MM and axons in the anteroventral / anteromedial thalamic nuclei and Gudden's ventral tegmental nucleus with EYFP. The EYFP-positive neurons in the MM were immunoreactive for glutamate and leu-enkephalin and received perisomatic GABAergic inputs. These results revealed monosynaptic projections from the subiculum to MM neurons projecting to the anteroventral / anteromedial thalamic nuclei and Gudden's ventral tegmental nucleus. This monosynaptic connection may support a fast and robust signal flow through the hippocampal-mammillothalamic and hippocampal-mammillotegmental pathways.
bioRxiv (Cold Spring Harbor Laboratory), Oct 4, 2022
Characterization of interregional interactions in brain is essential for understanding the mechan... more Characterization of interregional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro ()-electrocorticography (ECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped ECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current ECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel ECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the ECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the ECoG device reached to the most ventral part of cerebral preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
following. First, LFP trace during REM epochs were band-pass filtered (5-12 Hz), yielding y(t). A... more following. First, LFP trace during REM epochs were band-pass filtered (5-12 Hz), yielding y(t). Amplitude of theta oscillations were derived from Hilbert transform of y(t), and peaks of theta oscillations were detected as the positive to negative zero crossings of the derivative dy/dt. Inter-peak intervals were smoothed using an eleven-sample rectangular kernel. Candidate epochs were detected if smoothed inter-peak intervals were shorter than 10 percentile of smoothed inter-peak intervals. The candidate epochs were identified as phasic REM epochs if the following criteria were all fulfilled. (1) Duration of an epoch was longer than 900 msec. (2) Minimum of smoothed inter-peak intervals during an epoch was shorter than 5 percentile of smoothed inter-spike intervals. (3) Mean amplitude of theta oscillations during an epoch was larger than mean amplitude of theta oscillations during the entire REM sleep. A total of 5844 sec (3.68 % of REM sleep episodes) was identified as phasic REM ep...
In the present study we provide the first systematic and quantitative hodological study of the ca... more In the present study we provide the first systematic and quantitative hodological study of the calbindin-expressing (CB+) principal neurons in layer II of the entorhinal cortex and compared the respective projections of the lateral and medial subdivisions of the entorhinal cortex. Using elaborate quantitative retrograde tracing, complemented by anterograde tracing, we report that the layer II CB+ population comprises neurons with diverse, mainly excitatory projections. At least half of them originate local intrinsic and commissural projections which distribute mainly to layer I and II. We further show that long-range CB+ projections from the two entorhinal subdivisions differ substantially in that MEC projections mainly target field CA1 of the hippocampus, whereas LEC CB+ projections distribute much more widely to a substantial number of known forebrain targets. This connectional difference between the CB+ populations in LEC and MEC is reminiscent of the overall projection pattern of the two entorhinal subdivisions.
Acquisition of Auditory Discrimination Mediated by Different Processes through Two Distinct Circuits Linked to the Lateral Striatum
The striatum, the central hub of cortico-basal ganglia loops, contains functionally heterogeneous... more The striatum, the central hub of cortico-basal ganglia loops, contains functionally heterogeneous subregions distinguished by the topographic patterns of structural connectivity. These subregions mediate various processes of procedural learning. However, it remains unclear when and how striatal subregions engage in a new learning of sensory stimulus-based decision-making. Here, we show that the anterior dorsolateral striatum (aDLS) and posterior ventrolateral striatum (pVLS) are activated in a different temporal pattern during the acquisition phase of auditory discrimination learning. The aDLS promotes the behavioral strategy by the stimulus-response association while suppressing those driven by the response-outcome association, and the pVLS is involved in forming and maintaining the stimulus-response strategy. These two subregions exhibit distinct event-related neuronal responses during the learning processes. Our findings demonstrate that aDLS and pVLS neurons integrate the new le...
Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2020
The hippocampus processes multimodal information, including place, time, speed, reward, and memor... more The hippocampus processes multimodal information, including place, time, speed, reward, and memory. However, how such information is distributed to multiple downstream areas remains poorly understood. The subiculum is the major hippocampal output structure that receives the hippocampal CA1 output and projects to multiple cortical/subcortical areas. Despite its anatomical importance, the nature of information distribution from the subiculum is unknown. We investigated this issue by optogenetically identifying the projection targets of subicular neurons during large-scale extracellular recordings in freely behaving rats. We introduced channelrhodopsin-2 and a 256-channel silicon probe into the subiculum, and implanted four optical fibers above subicular projection targets. Then, axonal projections of the recorded subicular neurons were determined by detecting antidromic spikes generated by blue-light irradiation to the projection targets. During multiple behavioral tasks and sleep, the subicular projection neurons were entrained to neural oscillations differentially and conveyed distinct information depending on the projection targets. These results suggest the prominent role of the subiculum in distributing hippocampal information to multiple downstream targets in a pathway-specific manner.
Synthetic spike data generated by a network of 1,000 Hodgkin-Huxley type neurons
This is the dataset used for evaluating the performance of the methods for estimating synaptic co... more This is the dataset used for evaluating the performance of the methods for estimating synaptic connectivity from multiple spike trains (Kobayashi et al., 2018 BioRxiv). See README file about the data format and the paper about the simulation procedure.<br>
architectonics and connectivity patterns (MacLean, 1990). However, the physiological mechanisms t... more architectonics and connectivity patterns (MacLean, 1990). However, the physiological mechanisms that allow segregation and integration of neuronal informa-tion in the highly interconnected cortical-hippocampal networks (Sporns et al., 2000) are poorly understood. and Borbely, 1997; Battaglia et al., 2004) as unique temporal windows to examine how neocortical, paleo-cortical (parahippocampal), and hippocampal networks integrate and segregate the activity of their neurons without the disadvantage of surgical or pharmacological manipulations. Do synchronous neocortical patterns associated with slow oscillations invade and affect all parahippocampal and hippocampal subregions equally
CA3 circuit model compressing sequential information in theta oscillation and replay
The hippocampus compresses the sequential information in a theta oscillation cycle and short-term... more The hippocampus compresses the sequential information in a theta oscillation cycle and short-term sequential activities during sharp-wave ripple while sleeping or resting; these processes are known as theta sequence and replay, respectively. The theta sequence is based on theta phase precession patterns of individual neurons. However, how these sequential neuronal activities are generated and how they store information about the outside environment remains unknown. We developed a hippocampal cornu ammonis (CA)3 computational model based on the biological CA3 circuit’s anatomical and electrophysiological evidence to address these. The model comprises theta rhythm inhibition, place input, and CA3-CA3 plastic recurrent connection. The model could compress the sequence of the external inputs and reproduce theta phase precession and replay, learn additional sequences, and reorganize previously learned sequences. A gradual increase in synaptic inputs, controlled by interactions between th...
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Papers by Kenji Mizuseki