Understanding the function of cortical neuronal networks requires knowledge on the properties and interactions between principal cells and GABAergic interneurons. Interneurons are startlingly diverse. Different groups of GABAergic cells form synapses selectively with each other or with distinct regions of pyramidal cell membrane. This complex connectivity provides a maximal flexibility in the formation and dissolution of assemblies of principal cells. As well as assuring the autonomy and independence of subsets of pyramidal cells, interneurons assure timing functions for a range of population oscillations at distinct frequencies associated with distinct behavioral states. Finally, distinct interneurons, targeting specific domains of principal cell membrane, can rapidly reconfigure the biophysical properties of principal cells. Since learning-related information enters the hippocampus via the entorhinal cortex and dentate area, we propose to examine how interneurons control network operations in these structures. First, we must recognize and separate the extracellular spike signatures of principal cells and different classes of interneurons. We will attempt to classify interneurons of the dentate gyrus and entorhinal cortex on the basis of their network affiliated properties and on their distinct biophysical and anatomical features. The discharge patterns of distinct inhibitory cell types during major types of network oscillation in the behaving rat will be characterized large scale recordings and anatomy of a subset of interneurons will be recovered by juxtacellular electroporesis of Neurobiotin in behaving rats. The physiologically derived groups will be confronted with dendritic and axon arbors and with molecular content of the labeled cells. Parallel slice work will compare features of extracellularly recorded spikes with intracellular action potentials of histologically identified interneurons. The resulting identification of interneuron types in the entorhinal cortex and dentate will let us examine how distinct cell types contribute to theta, gamma and slow oscillations and sharp waves and control the formation of principal cell assemblies during behavior. This work should enhance our knowledge of interneuron function and serve as a base to understand how inhibitory circuits may be compromised in learning difficulties as well as in schizophrenia, depression, Alzheimer's disease and some epileptic syndromes.
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| Khodagholy, Dion; Gelinas, Jennifer N; Buzsáki, György (2017) Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus. Science 358:369-372 |
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| Peyrache, Adrien; Schieferstein, Natalie; Buzsáki, Gyorgy (2017) Transformation of the head-direction signal into a spatial code. Nat Commun 8:1752 |
| Buzsáki, György; Llinás, Rodolfo (2017) Space and time in the brain. Science 358:482-485 |
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