The development of synaptic transmission is time-locked to early social behaviors in rats

Shovan Naskar,Andrzej W Cwetsch,Roberto Narducci,Edoardo Balzani,Laura Cancedda,Valter Tucci

doi:10.1038/s41467-019-09156-3

Abstract

The development of functional synapses is a sequential process preserved across many brain areas. Here, we show that glutamatergic postsynaptic currents anticipated GABAergic currents in Layer II/III of the rat neocortex, in contrast to the pattern described for other brain areas. The frequencies of both glutamatergic and GABAergic currents increased abruptly at the beginning of the second postnatal week, supported by a serotonin upsurge. Integrative behaviors arose on postnatal day (P)9, while most motor and sensory behaviors, which are fundamental for pup survival, were already in place at approximately P7. A reduction in serotonin reuptake accelerated the development of functional synapses and integrative huddling behavior, while sparing motor and sensory function development. A decrease in synaptic transmission in Layer II/III induced by a chemogenetic approach only inhibited huddling. Thus, precise developmental sequences mediate early, socially directed behaviors for which neurotransmission and its modulation in supragranular cortical layers play key roles.

Highlights

The development of functional synapses is a sequential process preserved across many brain areas
To investigate the temporal sequence of glutamatergic and GABAergic synaptogenesis per se—separate from the level of network activity—we recorded pharmacologically isolated miniature postsynaptic currents. The frequency of both glutamatergic and GABAergic mPSCs from pyramidal neurons in supragranular layers of the neocortex displayed an abrupt increase between P8 and P9
These data are consistent with the increased number of cells characterized by low activity (‘low activity cells’ in Supplementary Fig. 1a, see the methods for a quantitative definition) when we recorded GABAergic conductance compared to glutamatergic conductance between P2 and P10 (Supplementary Fig. 1a)

Summary

Introduction

The development of functional synapses is a sequential process preserved across many brain areas. Previous studies in the hippocampus revealed that GABAergic signaling is depolarizing and mildly excitatory during the first postnatal week of development, and the maturation of the glutamatergic system lags behind the GABAergic system[2] This developmental sequence is common to many brain regions[2], and allows neurons to mature at early stages driven by the mild excitation provided by GABA, while avoiding the toxic effects of strong excitation driven by glutamate[2,3]. We show that glutamatergic conductances anticipate GABAergic ones in the supragranular layer of the rat somatosensory cortex Both currents abruptly increase during the second postnatal week with a temporal profile that matches the developmental profile of huddling between littermates. Our findings provide evidence for the association between region-specific timely neurodevelopmental processes and the emergence of complex behaviors relevant for sociability

Methods

Results

Conclusion