Speaker: Josiah Boivin (Nedivi Lab) 

Title: Balancing excitation and inhibition in the developing mouse brain

Abstract: Despite the importance of inhibition for regulating developmental plasticity, the emergence of inhibitory neocortical innervation and synapse formation have not been well characterized. Inhibitory somatostatin (SST) neurons, which innervate pyramidal dendrites, play a key role in cortical signal processing but are particularly understudied in the context of developmental plasticity. Here, we use a genetic labeling strategy to visualize SST boutons and their resident synapses across development in the mouse visual cortex. We show that SST innervation fills in across all cortical layers simultaneously, with the sharpest increase occurring after eye opening and during the opening of the cortical critical period for ocular dominance plasticity. Using epitope-preserving Magnified Analysis of Proteome (eMAP) to visualize individual synapses on each SST bouton, we found that before eye opening, many boutons are present without resident inhibitory synapses, and the number of synapses per bouton increases across development. Surprisingly, SST bouton and synapse formation are unaffected by dark-rearing, suggesting that the development of SST innervation does not require visual experience.  Our results show that in contrast to the developmental trajectory of excitatory circuitry, which follows a deep to shallow progression and goes through an exuberant growth phase followed by pruning, inhibitory innervation emerges concurrently across layers and progresses steadily without subsequent pruning. Further, unlike excitatory circuit development, inhibitory SST innervation and synapse formation appear independent of visual experience. These findings suggest that inhibitory innervation follows fundamentally different rules than excitatory innervation during development.