Optogenetic dissection of orbitofrontal to motor cortex circuits for behavioral flexibility

• Applicant: Dr. Verena Senn, since 7/2015
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255197095

The ability to behave in a flexible manner is an essential skill of humans and animals to survive in a changing environment. Behavioural flexibility requires multiple cognitive processes including recognition of new outcomes to older behaviours, inhibition of the outmoded responses and adaptation of behaviour accordingly. This process is thought to depend on top-down modulation by the prefrontal cortex over lower-order circuits that reach motor cortex through a prefrontal-striatal-thalamic loop. However, the prefrontal cortex also projects directly to cortical areas involved in movement generation through a cortical path. The role of the cortico-cortical connections remain elusive by now. The proposed project aims to investigate the functional prefrontal-motor cortex connectivity that supports response initiation and inhibition in behavioural flexibility. Specifically, we will focus on disentangling the projections from orbitofrontal cortex to motor cortex and compare them to the OFC to striatum connections. We aim to investigate how the interaction between the cortical and the subcortical pathways is coordinated and how this affects motor behaviour. To understand the role of OFC-motor cortex circuits we will dissect the projection pathways from OFC supplementary motor (premotor) cortex and characterize discrete cell populations within these paths. To achieve this, we will use advanced projection-based optogenetic manipulation techniques in combination with in vivo approaches. From rats, involved in a behavioural flexibility task, we will record neural activity in anatomically identified neurons within motor cortical areas, and ask how incoming prefrontal input modulates these cells. This approach promises to advance our understanding of complex neural activities in motor cortex during flexible behaviour. Comparing responses of neurons directly influenced through OFC with other motor cortex neurons might shed new light on the various response types within motor cortical areas. Furthermore, the detailed dissection of the mechanisms underlying behavioural flexibility will increase our knowledge of decision making in neuronal circuits, and may also further our understanding of certain behavioural disorders, since disturbances in behavioural flexibility have been associated with disorders such as schizophrenia and obsessive-compulsive disorder.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Professorin Dr. Ilka Diester, until 7/2015