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Duke Neurobiology Invited Seminar: Gordon Fishell: Making up your mind: the generation of interneuron diversity and their integration into cortical circuits


Gordon Fishell

Classic work from two decades ago demonstrated that inhibition is mediated through an array of over 50 discrete cortical cell types . Each of these possess unique shapes and properties, suggesting that they have specific roles in the brain. Despite this, our understanding of how these interneurons are assembled into functional cortical circuits is lacking. Parvalbumin and somatostatin interneurons, the two largest populations of inhibitory cortical cells are generated in a specialized region of the subcortex, known as the medial ganglionic eminence. Amazingly, both these cell types migrate during development across the brain to form canonical circuits with excitatory cortical cells. By studying their gene expression during their incorporation into cortical circuitry, we have discovered key regulators of their development, which provided us with the tools to interrogate the different subtypes and witness and perturb their development. These advances provided the tool kit to start tackling two big questions. How do these cells find their right excitatory cell partners in the brain and just how selective are these connections? In this talk, I will focus on the somatostatin populations, which we have recently found selectively connect to different excitatory populations, with one type targeting corticofugal cells and the other targeting intercortical relay neurons. Moreover, it seems these relationships depend on excitatory cells providing signals to the interneurons when they arrive in the cortex. The output and relay excitatory cells, which reside in different layers, appear to provide "instructions" to somatostatin cells as they settle within the cortex, allowing them to literally "learn on the job". This indicates the existence of a lock and key specificity in connectivity that we are only beginning to understand.


Lecture/Talk, Research