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Role of MGE- and CGE-derived Interneuron Subtypes in Transplant-induced Cortical Plasticity

  • Author(s): Tang, Yunshuo
  • Advisor(s): Alvarez-Buylla, Arturo
  • et al.
Abstract

Cortical GABAergic interneurons have been shown to play a pivotal role in ocular dominance plasticity (ODP) during the developmental critical period. GABAergic interneurons are extremely diverse, and currently it is unclear which interneuron subtypes contribute to critical period plasticity. The majority of cortical GABAergic interneurons originate from the medial and caudal ganglionic eminences (MGE and CGE, respectively). Transplanted into the visual cortex of postnatal animals, MGE-derived interneuron precursors can disperse, mature, integrate into local visual cortical circuit, and open a second window of critical-period-like plasticity. Because transplanted MGE precursor cells differentiate primarily into parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) cells, we genetically ablated PV+ or SST+ cells in the transplants and tested whether the remaining cells can induce plasticity in the recipients. Surprisingly, removing PV+ cells did not prevent MGE transplants from inducing plasticity, despite strong evidence linking PV+ interneurons to critical period plasticity. Depleting SST+ cells did not abolish transplant-induced plasticity, either, but removing both PV+ and SST+ cells eliminated plasticity. Our results show that SST+ interneurons, which are abundant and powerful inhibitors in the visual cortex but have scarcely been studied in the context of ODP, are as competent as PV+ interneurons in mediating plasticity.

To investigate the contribution of other interneuron subtypes to critical period plasticity, we transplanted CGE-derived interneuron precursors into postnatal recipients. Cells from CGE transplants migrated into the visual cortex as efficiently as MGE-derived interneurons. CGE-derived precursor cells did not differentiated into PV+ or SST+ cells, but instead generated interneurons expressing diverse subtype markers such as reelin, calretinin, and vasoactive intestinal peptide. Despite successful engraftment and efficient migration, CGE-derived interneurons failed to induce plasticity. Our results demonstrate that transplanted interneuron precursors from both MGE and CGE migrate vigorously in the postnatal cortex and differentiate into a diverse panel of cortical interneuron subtypes. However, only PV+ and SST+ interneurons derived from the MGE can modify host neural circuits and reintroduce juvenile-like plasticity into the adult cortex. These findings provide important insights into the functional application of interneuron subtypes. Such information will be crucial in investigating the mechanisms of critical period plasticity and devising effective strategies of transplant therapy.

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