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Matricryptins Trigger Inhibitory Synapse Formation in the Developing Neocortex, Mike Fox, PhD
October 6, 2016 @ 4:10 pm - 4:35 pm
Mike Fox, PhD, Associate Professor, Virginia Tech Carilion Research Institute and Director of the VTCRI Developmental and Translational Neurobiology Center —
Although inhibitory synapses comprise only ~20% of the total synapses in the mammalian cerebrum, they play essential roles in controlling neuronal activity. In fact, perturbing inhibitory synapses is associated with complex brain disorders, such as schizophrenia. Although many types of inhibitory synapses exist, these disorders have been strongly linked to defects in inhibitory synapses formed by Parvalbumin-expressing interneurons. Despite their importance, we lack a complete understanding of the mechanisms that underlie these Parvalbumin+ GABAergic synapses. Here, we present a role for an unconventional collagen â€“ Collagen XIX â€“ in the formation of Parvalbumin+ GABAergic synapses. Loss of this collagen results in decreased numbers of GABAergic synapses and in the acquisition of schizophrenia-related behaviors. Finally, studies presented here reveal a proteolytically shed fragment of Collagen XIX (termed a matricryptin) triggers nerve terminal assembly. Taken together, these findings reveal a novel role for collagens in the formation of cortical circuits associated with complex brain disorders.