PLASTICITY IN EXCITATORY INTERNEURONS OF THE ADULT OLFACTORY BULB DURING SPONTANEOUS POST-INJURY REGENERATION OF SENSORY INPUTS

Successful recovery after nervous system injury requires not only the restoration of damaged projections, but also appropriate processing of restored input by downstream circuits. How do target circuits change during denervation and re-innervation? We addressed this question by studying a unique model of naturally occurring regeneration in the adult mammalian brain. After a single dose of the olfactotoxin methimazole, olfactory sensory neurons in the nasal olfactory epithelium degenerate and are subsequently replaced via local neurogenesis. This process leaves their target structure in the brain – the olfactory bulb (OB) – transiently denervated before being reinnervated by new axonal inputs. Using immunohistochemistry and acute slice electrophysiology, we studied the changes occurring in OB circuits during this process of naturally occurring input regeneration. We focused especially on external tufted cells (ETCs), a class of excitatory glutamatergic interneurons that play a key role in amplifying sensory inputs in the OB’s glomerular layer. During the initial phase of post-injury re-innervation, we found that ETCs had lower levels of baseline activity as revealed by expression of the immediate early gene c-fos. Despite this, ETCs’ intrinsic membrane properties, their axon initial segment location and length, and their gross dendritic morphology were all unchanged compared to non-injured controls. We did, however, observe a decrease in ETC dendritic spine density, and an increase in spontaneous long-lasting excitatory events during post-injury regeneration. This suggests that input-specific changes to a key interneuron subtype may play a crucial role in regulating target circuit function during naturally occurring recovery from nervous system damage.