Dendritic signal processing and functional compartmentalization in GABAergic interneurons

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Dendrites correspond to a receiving apparatus of the neuron, integrating the vast majority of synaptic inputs over time. Dendrites exhibit a large diversity of active ion conductances and, therefore, operate as non-linear signaling devices. Calcium signal represents an important aspect of dendritic integration. It may have different spatial and temporal ranges of action, and can exert various functions from induction of synaptic plasticity to local tuning of neuronal firing. Recent methodological advances, including the ability to monitor optically local Ca2+ elevations in dendritic compartments using two-photon microscopy in brain slices and in vivo, have enabled the close observation of the processes that occur within dendrites and of the manner via which information received from synapses is transformed into a neural code and modified by changes in activity during dendritic development and plasticity. Nonetheless, the mechanisms and roles of active dendritic processes in dendrites of different cell types remain unexplored. Local circuit GABAergic interneurons control the integration and transfer of information in many brain regions. Despite the fact that different types of interneurons exhibit a highly complex dendritic organization, with a large variety of voltage-gated ion conductances and specific neurotransmitter receptors, interneuron dendrites have received little attention. We propose to explore the activity-dependent recruitment and the functional significance of active dendritic conductances at excitatory synapses of inhibitory interneurons using a combination of targeted somatic patch-clamp and sharp intracellular recordings, two-photon microscopy (Ca2+ imaging and uncaging), optogenetics, immunohistoshemistry, and neuroanatomy in brain slices and in vivo. As the functional organization of dendritic signal processing is fundamental for the learning, memory and higher cognitive functions affected in multiple neurological and mental health disorders, this study will be of value to cell biologists and neuroscientists working in the fields of cellular and system neuroscience and cognitive disorders.