Community Research and Development Information Service - CORDIS

Final Report Summary - HIPPOFRONTALSYN (Hippocampal-prefrontal synaptic transmission in cognitive function)

The prefrontal cortex (PFC) is a major information processing hub in the brain, integrating inputs from many different brain regions. The PFC is crucially required for goal-directed behaviour, cognitive processing and modulation of emotional responses. These diverse functions are thought to be supported by neurons of various types, forming intricate networks that are coupled with synaptic connections. Impairment in the function of these networks is thought to give rise to various neuropsychiatric disorders, including autism, major depression and schizophrenia. In this project we aimed at developing new methodologies for dissecting the role of defined inputs to the prefrontal circuit, combining state of the art optogenetic approaches with functional imaging and electrophysiology to gain a circuit-level understanding of the contribution of inputs from different brain regions to behavior. The PFC receives strong synaptic input from the hippocampus and basolateral amygdala, both limbic structures that are involved in processing spatial, mnemonic and emotional information. By manipulating the strength of synaptic input from the BLA to the PFC, we have been able to obtain insight into the direct contribution of this synaptic pathway to the formation of emotional memories.

Another important objective of this project was to better understand the contribution of dopamine (DA) and norepinephrine (NE), two important neuromodulatory transmitters, to the function and behavioral output of neural circuits in awake behaving animals. Using an innovative method for mapping synaptic connections, we are studying the effect of these two neuromodulators on synaptic connectivity within the PFC. By introducing light-activated channelrhodopsins into neurons located at the input regions, we are able to precisely activate these inputs while recording from identified and studying the impact of these neuromodulatory inputs over the functional properties of neural circuits and the correlation of their activity with behavior. In a recent study, we examined the role of dopaminergic neurotransmission on sexually-dimorphic behavior. We found that DA neurons located in the anterior ventral hypothalamus play a crucial role in the regulation of maternal behavior in female mice, and in suppression of aggressive behavior in male mice. We also identified a novel synaptic pathway supporting dopaminergic regulation over the secretion of oxytocin, a hormone implicated in numerous behavioral processes, including maternal behavior, pair bonding, lactation, anxiety and pain. Our work has further enhanced the understanding of the links between the activity of defined neural circuits and behavior.

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Life Sciences
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