Neuronal activity of pyramidal cells in the CA1 area of the hippocampus enables spatial navigation, learning and memory and their firing is tightly controlled by GABAergic interneurons. Both, pyramidal cells and interneurons are highly heterogeneous cell types. Different CA1 pyramidal cells project to distinct brain areas including the subiculum, entorhinal, retrosplenial, prefrontal cortex, olfactory bulb, striatum and/or hypothalamus. Distinct classes of interneurons innervate different subcellular domains of pyramidal cells and operate with different molecular machineries. However, how the different types of pyramidal cells and interneurons contribute to cognitive behaviour remains unknown. In the present proposal we will use novel techniques to test the hypothesis that different types of pyramidal cells and interneurons define spatio-temporal circuitries in the hippocampus of freely-moving rodents underlying cognitive processing. We will test if pyramidal cells projecting to different brain areas make different contribution to spatial information coding, prospective coding for future choices and memory consolidation during sleep. Also, we will determine how identified classes of GABAergic interneurons control pyramidal cell activity and network oscillations during cognitive tasks in freely-moving rats. In addition, we will use transgenic mice in order to up- or down-regulate quickly and reversibly the activity of specific classes of neurons and determine their causal contribution to network operations and cognitive behaviour. Our experiments will determine spatio-temporal codes in and beyond the hippocampal circuit by defining simultaneously the neuronal activity and synaptic connectivity of identified neurons during cognitive behaviours, learning and memory.
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