Gord Fishell, PhD
Professor of Neurobiology
Harvard Medical School and the Broad Institute
Host(s): Maria Tosches (Faculty)
Making up your mind: The integration of interneurons into cortical circuits
The mammalian cerebral cortex comprises a complex neuronal network that maintains a delicate balance between excitatory neurons and inhibitory interneurons. Previous studies, including our own research, have shown that specific interneuron subtypes are closely associated with particular pyramidal neuron types, forming stereotyped local inhibitory microcircuits. However, the developmental processes that establish these precise networks are not well understood. Here we show that pyramidal neuron types are instrumental in driving the terminal differentiation and maintaining survival of specific associated interneuron subtypes. In a wild-type cortex, the relative abundance of different interneuron subtypes aligns precisely with the pyramidal neuron types with which they synaptically target. In Fezf2 mutant cortex, characterized by the absence of layer 5 pyramidal tract neurons and an expansion of layer 6 intratelencephalic neurons, we observed a corresponding decrease in associated layer 5b interneurons and an increase in layer 6 subtypes. Interestingly, these shifts in composition are achieved through mechanisms that are specific to different interneuron types. While SST interneurons adjust their abundance to the change in pyramidal neuron prevalence through the regulation of programmed cell death, parvalbumin interneurons alter their identity. These findings illustrate two key strategies by which the dynamic interplay between pyramidal neurons and interneurons allows local microcircuits to be sculpted precisely. These insights underscored the precise roles of extrinsic signals from pyramidal cells in the establishment of interneuron diversity and their subsequent integration into local cortical microcircuits.
Relevant Publications:
Cortical somatostatin interneuron subtypes form cell-type-specific circuits
Tuesdays@10 is a signature Zuckerman Institute initiative that aims to expose researchers at all levels to high-quality science and stimulate scientific discourse. The speakers featured in this series represent various fields and techniques in neuroscience, and include invited guests of the Columbia Neuroscience Seminars, the Zuckerman Institute's Local Circuits Affiliates Program, and other special seminar series through a combined, collaborative effort of one or more of the following: Columbia's Zuckerman Institute, the Center for Precision Psychiatry, the Center for Theoretical Neuroscience, the Department of Neuroscience, the Doctoral Program in Neurobiology and Behavior and the Columbia Translational Neuroscience Initiative, and with support from the Kavli Institute for Brain Science.
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