大脳皮質回路の動作原理解明への最前線
Uncovering functional principles of cortical circuits
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Neural Coding and Project MindScope at The Allen Institute
○R. Clay Reid1
Allen Institute for Brain Science1

Local circuits in the cerebral cortex consist of tens of thousands of neurons, each of which makes and receives thousands of connections. A major impediment to understanding these circuits is that we have no wiring diagrams of their interconnections. But even if we had a wiring diagram, understanding the network would also require information about each neuron's function. Recently, we have demonstrated that the relationship between structure and synaptic connectivity can be studied in the cortex by combining in vivo physiology with subsequent network anatomy with electron microscopy (Bock et al., Nature, 2011), leading towards a functional connectome. This research program is continuing as part of a larger program at the Allen Institute, called MindScope, that seeks to examine the computations that lead from visual input to behavioral responses by observing and modeling the physical transformations of signals in the cortico-thalamic visual system of mice (Koch and Reid, Nature, 2012. I will describe other aspects of this program, including calcium imaging experiments to examine the physiological properties of pyramidal neurons that project between different cortical areas: the functional projectome.
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Excitatory and inhibitory microcircuit underlying visual cortial processing
○Yang Dan1
University of California, Berkeley1


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Synapse reorganization in formation of motor memory
○Yi Zuo1
University of California, Santa Cruz1

One fundamental question in neuroscience is how the brain processes and stores information. As the information-processing elements in the brain, neurons communicate via specialized connections called synapses. The majority of excitatory synapses reside at dendritic spines, which thus serve as a good proxy for synaptic connectivity. Using transcranial two-photon microscopy to visualize fluorescently-labeled neurons in the brain of transgenic mice (YFP-H line), our recent studies followed the dynamics of spines on apical dendrites of L5 pyramidal neurons in the motor cortex during different forelimb specific motor learning. We found that novel tasks lead to rapid emergence of new spines on dendrites of pyramidal neurons in the motor cortex. Subsequent training of the same task preferentially stabilizes these learning-induced spines, which persist long after training terminates and thus may provide a structural basis for durable motor memory. Furthermore, spines that emerge during repetitions of the same motor task tend to cluster along dendrites, whereas spines formed during tandem execution of different motor tasks do not cluster. This suggests that the spatial distribution of synapses is actively regulated in vivo, and may encode memory traces for motor tasks. These studies have established a research platform to follow synapse reorganization during learning over time in living mice, which enable further investigations into motor learning and memory.
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大脳皮質錐体細胞多様性と結合選択性
Cortical pyramidal cell subtypes and connection selectivity

○川口泰雄1,2,3
○Yasuo Kawaguchi1,2,3
自然科学研究機構 生理学研究所1, 総合研究大学院大学、岡崎2
National Institute of Physiological Sciences1, SOKENDAI, Okazaki2, JST-CREST, Tokyo3

Pyramidal cells, especially those in layer 5 (L5), provide cortical output by sending axons to a variety of subcortical areas. However, their functional composition has not yet been fully elucidated. In addition to providing cortical output, pyramidal neurons also form diverse excitatory recurrent subnetworks locally within the cortex. To understand how these excitatory subnetworks generate discreet and parallel output, we are investigating the characteristics of L5 pyramidal neurons in the rat frontal cortex according to their subcortical projection targets, including crossed-corticostriatal (CCS) neurons that project to the contralateral striatum as well as ipsilateral one, and corticopontine (CPn) neurons that project to the ipsilateral pons. Experiments involving pairs of CCS and/or CPn neurons revealed distinct synaptic connectivity patterns in these two classes of L5 pyramidal neuron. CPn/CPn and CCS/CCS pairs had similar connection probabilities, but CPn/CPn pairs exhibited greater reciprocal connectivity, stronger unitary synaptic transmission, and more facilitation of paired-pulse responses. Further, we observed a unidirectional connectivity from CCS neurons to CPn neurons, with few, if any, connections in the opposite direction. Finally, CCS and CPn neurons had morphological differences in their apical dendritic trees, suggesting potential differences in afferent input and synaptic integration. Here we combined these results with the known corticostriatal and basal ganglia internal structures to propose a functional relationship between local intracortical excitatory subnetworks and more global cortico-basal ganglia-thalamic subnetworks. Recently it has been proposed that most of GABAergic interneurons make synapses on nearby pyramidal cells in a non-selective manner, but the intracortical inhibitory system may be organized according to these pyramidal projection subtypes.
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Direct lineage reprogramming of postmitotic callosal neurons into corticofugal neurons in vivo
○Paola Arlotta1, Caroline Rouaux1
Harvard University1

Once programmed to acquire a specific identity and function, cells rarely change in vivo. Neurons of the mammalian central nervous system (CNS) in particular are a classic example of a stable, terminally differentiated cell type. With the exception of the adult neurogenic niches, where a limited set of neuronal subtypes continue to be generated throughout life, CNS neurons are only born during embryonic and early postnatal development. Once generated, neurons become permanently postmitotic and do not change their identity for the life span of the organism. Here, we have investigated whether excitatory neurons of the neocortex can be instructed to directly reprogram their identity postmitotically from one subtype into another, in vivo. We show that embryonic and early postnatal callosal projection neurons (CPN) of layer II/III can be postmitotically lineage reprogrammed into layer V/VI corticofugal projection neurons (CFuPN) upon expression of the transcription factor Fezf2. Reprogrammed callosal neurons acquire molecular properties of corticofugal projection neurons and change their axonal connectivity from interhemispheric, intracortical projections to corticofugal projections directed below the cortex. The data indicate that during a window of postmitotic development neurons can change their identity, acquiring critical features of alternate neuronal lineages.

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