Developmental Regulation of Homeostatic Plasticity in Mouse Primary Visual Cortex

Homeostatic plasticity maintains network stability by adjusting excitation, inhibition, or the intrinsic excitability of neurons, but the developmental regulation and coordination of these distinct forms of homeostatic plasticity remains poorly under-stood. A major contributor to this information gap is the lack of a uniform paradigm for chronically manipulating activity at different developmental stages. To overcome this limitation, we used designer receptors exclusively activated by designer drugs (DREADDs) to directly suppress neuronal activity in layer2/3 (L2/3) of mouse primary visual cortex of either sex at two important developmental timepoints: the classic visual system critical period [CP; postnatal day 24 (P24) to P29], and adulthood (P45 to P55). We show that 24 h of DREADD-mediated activity suppression simultaneously induces excitatory syn-aptic scaling up and intrinsic homeostatic plasticity in L2/3 pyramidal neurons during the CP, consistent with previous obser-vations using prolonged visual deprivation. Importantly, manipulations known to block these forms of homeostatic plasticity when induced pharmacologically or via visual deprivation also prevented DREADD-induced homeostatic plasticity. We next used the same paradigm to suppress activity in adult animals. Surprisingly, while excitatory synaptic scaling persisted into adulthood, intrinsic homeostatic plasticity was completely absent. Finally, we found that homeostatic changes in quantal in-hibitory input onto L2/3 pyramidal neurons were absent during the CP but were present in adults. Thus, the same population of neurons can express distinct sets of homeostatic plasticity mechanisms at different development stages. Our findings sug-gest that homeostatic forms of plasticity can be recruited in a modular manner according to the evolving needs of a develop-ing neural circuit.

Automated summary

Homeostatic plasticity in neural circuits can be modulated differently at various developmental stages, with excitatory synaptic scaling and intrinsic homeostatic plasticity being induced during critical periods but only excitatory synaptic scaling persisting into adulthood. This suggests that distinct sets of homeostatic plasticity mechanisms are recruited based on the needs of the developing neural circuit.