Control of spontaneous activity patterns by inhibitory signaling in the developing visual cortex

Abstract

During early development, even before the senses are active, bursts of activity travel across the nervous system. This spontaneously generated activity drives the refinement of synaptic connections, preparing young networks for patterned sensory input. Synaptic fine-tuning relies not only on the presence of spontaneous activity, but also on the specific characteristics of these activity patterns, such as their frequency, amplitude and synchronicity. Here, we provide evidence that these crucial characteristics are shaped by the relative balance of excitation and inhibition, where patterns with distinct characteristics have different excitatory/inhibitory ratios. Inhibition can control whether cells participate during a spontaneous event, as pharmacogenetic suppression of the somatostatin (SST) expressing subtype of inhibitory interneurons increased cell recruitment and lateral spread of events. KeywordsMouse, in vivo, pharmacogenetics, somatostatin expressing interneuron, VIP expressing interneuron, calcium imaging, DREADD

Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

“…Finally, we analyzed whether the distance between neurons determined the oxytocin effect and found that the oxytocin-mediated decrease in correlation increased with interneuronal distance (Fig. 3e, f), possibly reflecting increased lateral inhibition via SST + interneurons (see below 27,28 ). c. Network event frequency during baseline and after oxytocin application.…”

“…Finally, we asked whether the oxytocin-mediated decrease in frequency of spontaneous network activity was the result of the activation of oxytocin receptors expressed in SST + interneurons in vivo. We specifically inactivated SST + interneurons by using a Cre-dependent inhibitory DREADD delivered by virus injections, which results in 80% of the SST + interneurons expressing the hM4Di-DREADD construct 28 . Bath application of clozapine in vitro reduced the excitability of SST + interneurons 28 , replicating previous findings that hM4Di-DREADD activation reduces the excitability of developing layer 2/3 neurons 36 .…”

“…We specifically inactivated SST + interneurons by using a Cre-dependent inhibitory DREADD delivered by virus injections, which results in 80% of the SST + interneurons expressing the hM4Di-DREADD construct 28 . Bath application of clozapine in vitro reduced the excitability of SST + interneurons 28 , replicating previous findings that hM4Di-DREADD activation reduces the excitability of developing layer 2/3 neurons 36 . We performed in vivo wide-field calcium imaging to monitor spontaneous network activity in V1 and then activated the iDREADD receptor by injecting clozapine subcutaneously (Fig.…”

“…This decorrelation is mediated most likely by oxytocin-induced activation of SST + interneurons in agreement with previously published findings: activation of interneurons decreases neuronal correlations in general 51,52 . More specifically, lateral inhibition, a role attributed to SST + interneurons, decorrelates spike trains 53 or stimulus-evoked patterns 54 and pharmacogenetic inactivation of SST + interneurons increases pairwise correlations during spontaneous network activity in the developing visual cortex 28 . Our analyses suggest that correlations are down-regulated in a spatially specific manner: correlation decreases are more pronounced between pairs of relatively distant neurons.…”

“…Virus injections were performed at P0-1. pAAV-hSyn-DIO-hM4D(Gi)-mCherry and pAAV-hSyn-GCaMP6 plasmids were kindly packaged by Fred De Winter as described previously 28 . Immediately after injection, pups were kept warm on a heating pad and placed back to their mother after they awoke from anesthesia.…”