Ye Z, Mostajo-Radji MA, Brown JR, Rouaux C, Tomassy GS, Hensch TK, Arlotta P. Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons. Neuron. 2015 Nov 04; 88(3):475-83.

Citation

Ye Z, Mostajo-Radji MA, Brown JR, Rouaux C, Tomassy GS, Hensch TK, Arlotta P. 2015. Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons. Neuron. 88(3):475-83. Pubmed: 26539889 DOI:S0896-6273(15)00872-7

Abstract

During development of the cerebral cortex, local GABAergic interneurons recognize and pair with excitatory projection neurons to ensure the fine excitatory-inhibitory balance essential for proper circuit function. Whether the class-specific identity of projection neurons has a role in the establishment of afferent inhibitory synapses is debated. Here, we report that direct in vivo lineage reprogramming of layer 2/3 (L2/3) callosal projection neurons (CPNs) into induced corticofugal projection neurons (iCFuPNs) increases inhibitory input onto the converted neurons to levels similar to that of endogenous CFuPNs normally found in layer 5 (L5). iCFuPNs recruit increased numbers of inhibitory perisomatic synapses from parvalbumin (PV)-positive interneurons, with single-cell precision and despite their ectopic location in L2/3. The data show that individual reprogrammed excitatory projection neurons extrinsically modulate afferent input by local PV(+) interneurons, suggesting that projection neuron class-specific identity can actively control the wiring of the cortical microcircuit.

Related Faculty

Paola Arlotta, Ph.D.

Arlotta Lab

Dr. Arlotta is interested in understanding the molecular laws that govern the birth, differentiation and assembly of the cerebral cortex, the part of the brain that controls how we sense, move and think. She integrates developmental and evolutionary knowledge to investigate therapies for brain repair and for modeling neuropsychiatric disease.