Input-Independent Homeostasis of Developing Thalamocortical Activity

Abstract

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 STATEMENTUncovering 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.

Activity in developing prefrontal cortex is shaped by sleep and sensory experience

“…As expected ( Dooley et al, 2021 ; Glanz et al, 2021 ; Gómez et al, 2021 ), pups spent more time in AS than wake at P8 (AS: 57.7 ± 2.5%; wake: 30.9 ± 1.9%) and P12 (AS: 44.0 ± 3.6%; wake: 39.3 ± 3.5%). Also, the transition from discontinuous cortical activity at P8 to continuous activity at P12 was evident in all three areas, as described previously in primary somatosensory, motor, and visual cortex ( Golshani et al, 2009 ; Rochefort et al, 2009 ; van der Bourg et al, 2017 ; Glanz et al, 2021 ; Riyahi et al, 2021 ).…”

Experience dependence of alpha rhythms and neural dynamics in mouse visual cortex

“…Our results indicate however that homeostatic set-points can be altered by the profound changes in excitatory and inhibitory circuits resulting from visual deprivation (Ribic, 2020). While enucleation at P6--when spontaneous firing rates are 10% of adults (Riyahi et al, 2021)--did not significantly change adult firing rates, binocular deprivation–a procedure that causes less acute reduction in firing-rates and allows for greater homeostatic plasticity in adults (Hengen et al, 2013; Keck et al, 2013)--did lower firing-rates, but only during Stationary periods. It is unclear whether mean firing-rates were truly lower in sutured animals and an increased movement-related signal normalized them, or whether the firing-rate set points are similar in both animals but set during the movement period.…”

“…Here we examined the effect of two forms of early-life blindness on the establishment and maintenance of cortical dynamics. Bilateral enucleation at P6 or P13 allows us to compare the effect of retinal input removal before and after the onset of mature dynamics (Riyahi et al, 2021), without the significant thalamic and cortical rewiring caused by earlier loss of retinal inputs in mice (Olavarria and Hiroi, 2003; Golding et al, 2014). Binocular eyelid suture initiated before eye-opening deprives the animal of pattern vision and the ability to guide behavior visually, while preserving luminance detection and circadian rhythms (Kampf-Lassin et al, 2011), similar to bilateral cataracts.…”

Synaptic and circuit mechanisms prevent detrimentally precise correlation in the developing mammalian visual system

“…We found that PCA of model parameters could be useful for qualitative assessment of EMO quality and heterogeneity of obtained models. Second, to set the strength of retinal inputs, we used the firing rate of TC neurons observed in vivo and ‘functionally’ estimated synaptic conductance at this age by assuming that total synaptic conductance is subject to homeostatic regulation and firing rate is the target activity parameter ( Riyahi et al, 2021 ). Using homeostatic regulation to set synaptic conductance is critical for modeling heterogeneous networks, where a single value for synaptic conductance would not work for all neurons.…”