Vesicular GABA transporter is necessary for transplant-induced critical period plasticity in mouse visual cortex

Abstract

The maturation of GABAergic inhibitory circuits is necessary for the onset of the critical period for ocular dominance plasticity in the postnatal visual cortex (Espinosa & Stryker, 2012; Hensch, 2005). When it is deficient, the critical period does not start. When inhibitory maturation or signaling is precocious, it induces a precocious critical period. Heterochronic transplantation of GABAergic interneuron precursors derived from the medial ganglionic eminence (MGE) can induce a second period of functional plasticity in the visual cortex (Southwell, 2010). While the timing of MGE transplant-induced plasticity is dictated by the maturation of the transplanted cells, its mechanisms remain largely unknown. Here we sought to test the effect of blocking vesicular GABA loading and subsequent release by transplanted interneurons on the ability to migrate, integrate, and induce plasticity in the host circuitry. We show that MGE cells taken from male and female donors that lack vesicular GABA transporter (Vgat) expression disperse and differentiate into somatostatin- (SST) and parvalbumin- (PV) expressing interneurons upon heterochronic transplantation in the postnatal mouse cortex. While transplanted Vgat mutant interneurons come to express mature interneuron markers and display electrophysiological properties similar to those of control cells, their morphology is significantly more complex. Significantly, Vgat mutant MGE transplants fail to induce ocular dominance plasticity, demonstrating the pivotal role of vesicular GABAergic transmission for MGE transplant-induced plasticity in the postnatal mouse visual cortex.

SIGNIFICANCE STATEMENT

Embryonic inhibitory neurons thrive when transplanted into postnatal brains, migrating and differentiating in the host as they would have done if left in the donor. Once integrated into the host, these new neurons can have profound effects. For example, in the visual cortex, such neurons induce a second critical period of activity-dependent plasticity when they reach the appropriate stage of development. The cellular mechanism by which these transplanted GABAergic interneurons induce plasticity is unknown. Here we show that transplanted interneurons that are unable to fill synaptic vesicles with GABA migrate and integrate into the host circuit, but they do not induce a second period of plasticity. These data suggest a role for the vesicular GABA transporter in transplant-mediated plasticity.