大脳皮質と海馬の抑制性細胞の機能解析
Inhibitory Neuron Function in Neocortex and Hippocampus
S1-2-3-1
Functional properties of GABAergic neurons in layer 2/3 mouse barrel cortex
○Carl C.H. Petersen1
Laboratory of Sensory Processing, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland1

A key goal of modern neuroscience is to understand the neural circuits and synaptic mechanisms underlying sensory perception. Here, I will discuss our efforts to characterise sensory processing in the mouse barrel cortex, a brain region known to process tactile information relating to the whiskers on the snout. Each whisker is individually represented in the primary somatosensory neocortex by an anatomical unit termed a 'barrel'. The barrels are arranged in a stereotypical map, which allows recordings and manipulations to be targeted with remarkable precision. In this cortical region it may therefore be feasible to gain a quantitative understanding of neocortical function. Here, I will focus on our efforts to obtain whole-cell membrane potential recordings from genetically-defined GABAergic neurons, visualised through two-photon microscopy in layer 2/3 of awake head-restrained mice. I will present the differential regulation of membrane potential dynamics in different subtypes of GABAergic neurons as a function of whisker behavior. In addition, I will discuss the function of GABAergic neurons in a simple learned whisker-dependent sensory task. These ongoing investigations begin to detail the functional operation of superficial GABAergic neurons and their sub-type specific properties.
S1-2-3-2
GABAergic neurones - the cellular substrate for local and long-range synchrony
○Hannah Monyer1
Dept. Clinical Neurobiology, Medical Faculty of Heidelberg University & DKFZ1

Over the past decade we used genetic manipulations to study the contribution of GABAergic interneurones for rhythmic synchronous activity. We focused on the hippocampus, and more recently on the medial entorhinal cortex, two brain structures that are crucially involved in spatial coding and spatial memory. Genetic manipulations included ablations of glutamate receptors or electrical coupling in GABAergic interneurones in the whole forebrain, or locally in the hippocampal-entohinal formation. Our studies underline the functional role of local GABAergic interneurones for spatial or temporal coding in the hippocampus. The genetic manipulations were always associated with distinct spatial memory deficits. These results will be summarized and discussed in the context of current models of memory formation and storage. In addition I will present data demonstrating the presence of long-range GABAergic cells that bilaterally connect the hippocampus and entorhinal cortex. Also these data will be discussed in a larger context, since there is good reason to believe that long-range GABAergic neurones are more abundant in the forebrain as previously thought. By virtue of their connectivity - the target cells are most often local interneurones - this class of cells is ideally suited to synchronize brain regions over long distance.
S1-2-3-3
Firing patterns of GABAergic interneurons during cognitive behavior
○Thomas Klausberger1
Medical University of Vienna, Austria1

The distributed temporal activity in neuronal circuits of the hippocampus combines emotional information with episodic and spatial memory to guide behavioural action. In the hippocampus of rodents, single neurons of unknown identity exhibit specific firing patterns during spatial navigation and decision-making tasks. The hippocampus consists of highly diverse neuronal types with distinct synaptic connectivity, molecular expression profile and contribution to network activity. Neurons can be divided into excitatory pyramidal cells, which use glutamate as a neurotransmitter and give both local and long-range axonal projections, and inhibitory interneurons, which are GABAergic and control the activity and timing of pyramidal cells mainly through local axons. These neurons can be further subdivided on the basis of their distinct axo-dendritic arborisations, subcellular post-synaptic targets, and by their differential expression of signalling molecules, including receptors, ion channels, neuropeptides, transcription factors and Ca2+ binding proteins. We have recorded from identified GABAergic interneurons and pyramidal cells in the hippocampus of freely-moving as well as anaesthetised rats using the juxtacellular recording and labelling technique and investigated their contribution to behavioural states and network oscillations. Our results indicate that different GABAergic interneurons release GABA at distinct times to different domains of pyramidal cells explaining the need of diverse classes of interneurons and thereby contributing to the formation of cell assemblies and representations in the hippocampus.
S1-2-3-4
Structural plasticity of neocortical inhibitory circuits
○Elly Nedivi1, Katherine Villa1, Kalen Berry1, Jerry Chen1
Massachusetts Institute of Technology, U.S.A.1

The role of inhibition within the cortical circuit has recently gained prominence as it has become clear that the balance of excitation/inhibition is critical to proper brain development as well as for cognitive function. Indeed, many mental and neuropsychiatric diseases have been linked to deficits in inhibitory function. Yet our understanding of how inhibitory connectivity is modified by experience and how that relates to the excitatory network is minimal. We previously showed that dendrites of inhibitory interneurons in the adult visual cortex remodel on a day-to-day basis and that experience can drive the structural remodeling of interneuron dendrites and axons in an input- and circuit-specific manner. A major obstacle to visualizing the synaptic correlates of inhibitory arbor remodeling, as well as how it may be coordinated with remodeling of excitatory inputs, has been the inability to visualize inhibitory synapses in vivo. Recently, we developed high-resolution multi-color two-photon microscopy to simultaneously monitor inhibitory synapse, excitatory synapse, and dendritic spine remodeling across the entire dendritic arbor of cortical L2/3 pyramidal neurons in vivo during normal and altered sensory experience. This has allowed us to address, for the first time, fundamental questions about the interplay between excitatory and inhibitory synaptic transmission during normal adult brain function as well as experience-dependent plasticity.
S1-2-3-5
大脳皮質FSバスケット細胞から錐体細胞への抑制性シナプス結合特性
Locally limited conductance of IPSCs elicited by fast spiking interneurons synapsing onto cortical pyramidal cells

○窪田芳之1,2,3
○Yoshiyuki Kubota1,2,3
生理学研究所1, 総合研究大学院大学2
National Institute for Physiological Sciences, Japan1, SOKENDAI, Okazaki, Japan2, JST-CREST, Tokyo, Japan3

Little is known about the functional mechanism of inhibition during the integration of synaptic signals in cortical pyramidal cell. Thus, paired recordings were obtained from fast-spiking (FS) basket and pyramidal cells in layer V of rat prefrontal cortex. IPSC amplitudes were measured at the pyramidal cell soma, followed by quantitative light/electron microscopic (LM/EM) 3D reconstructions of the pairs to reveal the location of synaptic contacts and synaptic junction structure. Cortical FS basket cells provide three distinct modalities of inhibition, on somata, dendrites and spines of the postsynaptic pyramidal cells. Somatic inhibition was most efficient and strong, whereas inhibition on dendrites and spines is locally restricted and weaker, however dependent on the geometric distance of synaptic contacts to the soma. The three modes of inhibition are directly correlated to the size of the junction area. Using this maneuver inhibitory synapse intercepts excitatory signal inputs on the target cells efficiently.

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