Sol Feiguin
Research Mentor: Gabriel Corfas
Mentor Department: Kesge Hearing Research Institute, Medicine
Author(s): Beatriz Borges Del Grande, Gabriel Corfas, Sol Feiguin
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 56
Abstract
Social isolation during the juvenile period (JSI) disrupts prefrontal cortex (PFC) myelination and function. Previous work from our group demonstrated that many long-term effects of JSI are mediated by reduced expression of type III Neuregulin 1 (NRG1), a key regulator of myelination, neural development, and plasticity. JSI from postnatal day (P)21–P35, a critical developmental window, induces a persistent reduction in PFC NRG1 expression, resulting in impaired ErbB receptor signaling in oligodendrocytes, delayed oligodendrocyte maturation, and hypomyelination of PFC neurons. Although myelination was long thought to be restricted to excitatory neurons, recent evidence shows that inhibitory interneurons are also myelinated; however, the functional significance of this remains poorly understood. Using RNAscope, we found that type III NRG1 is expressed by both excitatory and inhibitory neurons in the PFC. To examine the effects of JSI on inhibitory parvalbumin-expressing (PV+) neurons and their myelination, wild-type mice were either group-housed or isolated from P21–P35. At P35, JSI mice exhibited reduced PV expression and decreased apparent PV+ neuronal density in the PFC. To distinguish between neuronal loss and altered maturation, we used PV-Cre::tdTomato mice to fate-map PV+ neurons. While colocalization of PV immunoreactivity with tdTomato labeling was ~85% in controls, it was reduced to ~52.5% following JSI, without a change in total tdTomato+ cell number. This indicates that JSI downregulates PV expression rather than causing PV+ neuron loss. Consistent with this, PV expression strongly correlated with myelin basic protein (MBP) levels. JSI reduced MBP+ axons, PV+ axons, and myelinated PV+ axons in the PFC. Notably, selective NRG1 knockdown in PV+ neurons phenocopied these effects. Together, these findings demonstrate that impaired NRG1/ErbB signaling following juvenile social isolation leads to hypomyelination of PV+ neurons and reduced parvalbumin expression in the PFC.
