EPFL Neuro Seminar //Ofer Yizhar: Optogenetic dissection of local and long-range connections in prefrontal circuits

Hybrid!

The prefrontal cortex (PFC) plays an important role in regulating multiple cognitive functions in mammals, and impairments in this region have been linked with behavioral dysfunction in psychiatric disorders. Neurons in the PFC connect with multiple brain-wide networks regulating behavior, and their long-range connections to different cortical and subcortical targets are thought to be involved in distinct behavioral functions. Specifically, long-range outputs from the PFC to the amygdala are known to be involved in emotional learning, social behavior and anxiety. I will describe a set of experiments aimed at understanding the structure of synaptic connectivity among amygdala-projecting neurons in the mPFC. Using single-neuron two-photon optogenetic stimulation and imaging, we demonstrated that these neurons form distinct connectivity modules in the deep and superficial layers of the mPFC. I will then descibe the engineering of a new class of optogenetic tools for silencing of long-range axonal projections between brain regions. I will focus on the development of eOPN3, a light-activated G-protein coupled receptor that couples to the inhibitory G_i/o signaling pathway and strongly suppresses synaptic release in vitro and in vivo. eOPN3 allows specific manipulation of long-range axonal connections, and can be used in behaving animals to understand the role of specific network connections in cognitive function and behavior.