Optogenetic dissection of local and long-range connections in prefrontal circuits

The prefrontal cortex (PFC) plays an important role in regulating social functions in mammals, and impairments in this region have been linked with social dysfunction in psychiatric disorders. The PFC plays a part in multiple brain-wide networks regulating behavior, and its long-range connections to different cortical and subcortical targets are thought to be involved in distinct behavioral functions. How is information about the multitude of cognitive/behavioral processes routed into and out of the PFC circuit? We are interested in understanding how PFC microcircuits process behavioral information, and how distinct PFC output neuron populations regulate learning, decision-making and social behavior.

I will first describe a set of experiments aimed at understanding the structure of synaptic connectivity among amygdala-projecting neurons in the mPFC. Using single-neuron twophoton optogenetic stimulation and imaging, we demonstrated that these neurons form unique connectivity modules in the deep and superficial layers of the mPFC. I will then describe our efforts to engineer new optogenetic tools for silencing of long-range axonal projections between brain regions. To efficiently suppress synaptic transmission, we engineered a new set of rhodopsin-based optogenetic tools that selectively couple to the Gi/o signaling pathway and strongly suppress synaptic release in vitro and in vivo.


Ofer obtained his PhD from the Tel Aviv University, working on molecular mechanisms of synaptic transmission. He did his postdoctoral work at Stanford University between 2008-2011, and joined the Weizmann Institute in 2011.

Ofer’s lab studies the organization, function and dysfunction of the prefrontal cortex. The prefrontal cortex is a brain region that plays important roles in many high-order processes, including working memory, emotion regulation, behavioral control, social behaivor and long-term memory.

Problems in prefrontal function are associated with various psychiatric disorders, including major depression, schizophrenia, autism and obsessive-compulsive disorders. The lab’s goal is to understand how this complex circuit operates and to gain a basic understanding of the mechanisms for its malfunction in disease states.