Input-independent homeostasis of developing thalamocortical activity

The isocortex of all mammals studied to date shows a progressive increase in the amount and continuity of background activity during early development. In humans the transition from a discontinuous (mostly silent, intermittently bursting) cortex to one that is continuously active is complete soon after birth and is a critical prognostic indicator. In the visual cortex of rodents this switch from discontinuous to continuous background activity occurs during the two days before eye-opening, driven by activity changes in relay thalamus. The factors that regulate the timing of continuity development, which enables mature visual processing, are unknown. Here we test the role of the retina, the primary input, in the development of continuous spontaneous activity in the visual cortex of mice using depth electrode recordings from Enucleated mice in vivo. Bilateral enucleation at postnatal day (P)6, one week prior to the onset of continuous activity, acutely silences cortex, yet firing rates and early oscillations return to normal within two days and show a normal developmental trajectory through P12. Enucleated animals showed differences in silent period duration and continuity on P13 that resolved on P16, and an increase in low frequency power that did not. Our results show that the timing of cortical activity development is not determined by the major driving input to the system. Rather, even during a period of rapid increase in firing rates and continuity, neural activity in the visual cortex is under homeostatic control that is largely robust to the loss of the primary input. SIGNIFICANCE STATEMENT Uncovering the mechanistic underpinnings of EEG development is critical to increasing the diagnostic potential of this cheap and portable methodology. An important component of this maturation is the acquisition of activity that is continuous, i.e. lacking silent periods. Here we used background activity in the visual cortex of developing unanesthetized mice to show that the primary sensory input plays little role in the development of continuity and normal firing rates, which instead appear to be regulated by mechanism internal to thalamus and cortex. These findings suggest that damage to driving thalamic inputs will be difficult to detect by EEG, and point to the importance of firing rate homeostasis in regulating even early development.