Neural circuitry underlies human behavior in all of its forms. High-level ‘Executive’ regions such as the prefrontal cortex (PFC) are the subject of particular interest as functional imaging, electrophysiological, and post-mortem studies have shown cellular and neurophysiological abnormalities in these regions associated with psychiatric disorders (e.g. schizophrenia, mood disorders, and addiction). The prefrontal cortex is one of the most highly interconnected regions of the brain, integrating inputs from widespread cortical and subcortical regions and transmitting information to an equally diverse set of targets. Major sources of synaptic input into the PFC include the thalamus and the hippocampus, which convey sensory, contextual and spatial information to be processed in the PFC and guide decision making and goal-directed behavior. A direct synaptic connection between the ventral hippocampus and the prefrontal cortex has been proposed to subserve the synchronization of activity between these two regions in defined behavioral states. Recent studies have indicated that the organization of PFC neurons that receive direct hippocampal input might support the entrainment of PFC activity to hippocampal theta oscillations. The goal of this proposal is to identify the prefrontal neuron population which receives direct hippocampal input and test the contribution of these neurons to cognitive processing and emotional states. Using an innovative combination of imaging approaches, electrophysiology and optogenetic techniques, we will first quantify the functional properties of hippocampal-prefrontal synapses and then examine the effects of neuromodulation on the properties of these synapses. Finally, through trans-synaptic labeling we will directly manipulate the activity of cells receiving monosynaptic hippocampal input and test the hypothesis that hippocampal-prefrontal theta phase-locking plays an important role in cognitive processing.
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