Morphological and molecular changes at dendritic spines orchestrate neuronal shifts in functional identity during monocular deprivation

Abstract

Experience‐dependent plasticity refers to the brain’s ability to sculpt and remodel its circuits in an experience‐dependent manner. In the binocular visual cortex, where inputs from both eyes converge onto single neurons, the relative responsiveness of a neuron to input from one eye can shift when that eye is deprived of input. Ocular dominance plasticity (ODP) is a well‐established model for experience‐dependent plasticity, and it is triggered by monocular deprivation (MD) by suturing an eyelid. This shift is classically measured by calculating the ocular dominance index (ODI), a measure of responsiveness to either eye. The cellular and molecular mechanisms for this reorganization during ODP are not well understood. We hypothesize that morphological and molecular changes at dendritic spines (synapses) allow for functional reprogramming of neurons. To test this, we introduced a plasmid into binocular neurons via single‐cell electroporation that encodes for the calcium sensor GCaMP6s, together with a structural marker mRuby2. Using two‐photon microscopy, spines were imaged in vivo in awake mice to determine their ODIs. We then imaged at later time points during MD to measure how spine size and their responsiveness was affected. Finally, the same neurons were visualized using magnified analysis of proteome (MAP), which evenly expanded tissue by 4X to closely examine scaffolding and transmission‐related proteins at the postsynaptic density. Preliminary data suggests that a combination of extensive spine loss and potentiation of few specific spines allows for shifts in responsiveness. In addition to synaptic plasticity being important for learning and memory in adulthood, many autism spectrum disorders (ASDs) have been associated with mutations in synaptic proteins. Investigation of the molecular mechanisms behind changes in synaptic morphology are therefore important to better understand the mechanisms of learning and memory, as well as these disorders.Support or Funding InformationThis research was supported by:IMSD R25GM076321 (JZ)NIH grants EY007023 and EY028219 (MS).