Objective The neocortex is organized into neural circuits that perform distinct computations, from sensory processing and motor control to memory, learning and language. Neuromodulatory systems projecting to the neocortex exert a powerful influence on cortical computations through neurotransmitters such as acetylcholine, monoamines and neuropeptides. The prefrontal cortex (PFC), a cortical region required for working memory, attention and goal-directed behavior, receives dense projections from multiple neuromodulatory systems that dramatically impact its function. Pioneering work has shown that pharmacological manipulation of these systems can potently modulate attention and cognitive function and that impaired neuromodulation can lead to psychiatric disease. Yet, much of the view of high level cortical function is focused on models that either ignore neuromodulation altogether or treat it as a reward or arousal signal.We propose to elucidate the dynamics and mechanisms of prefrontal neuromodulatory tuning, from the level of synapses and cells to circuits and animal behavior. To achieve this goal, we will map the circuit-level impact of synaptic neuromodulatory inputs on the prefrontal cortex circuit dynamics, develop and apply two novel optogenetic approaches for light-based synaptic silencing and optical recording of cortical neuromodulatory activity in vivo, and establish the causal roles of PFC neuromodulation in attention and working memory. These experiments will enable us for the first time to delineate the specific contribution of distinct neuromodulatory systems to prefrontal function, integrating comprehensive cell- and circuit-level analysis with unique opto-physiological readouts in behaving animals. The project will yield an integrative view of prefrontal neuromodulation, revealing its impact on cortical function and dissecting its roles in cognitive function. Fields of science natural sciencesbiological sciencesneurobiologycognitive neurosciencenatural sciencesbiological sciencesbiological behavioural sciencesethology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS5 - ERC Starting Grant - Neurosciences and neural disorders Call for proposal ERC-2013-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution WEIZMANN INSTITUTE OF SCIENCE EU contribution € 1 429 460,00 Address HERZL STREET 234 7610001 Rehovot Israel See on map Activity type Higher or Secondary Education Establishments Administrative Contact Gabi Bernstein (Ms.) Principal investigator Ofer Yizhar (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all WEIZMANN INSTITUTE OF SCIENCE Israel EU contribution € 1 429 460,00 Address HERZL STREET 234 7610001 Rehovot See on map Activity type Higher or Secondary Education Establishments Administrative Contact Gabi Bernstein (Ms.) Principal investigator Ofer Yizhar (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data