S100β‐mediated astroglial control of firing and input processing in layer 5 pyramidal neurons of the mouse visual cortex

Abstract

Inputs impinging on layer 5 pyramidal neurons perform essential operations as these cells represent one of the most important output carriers of the cerebral cortex. However, the contribution of astrocytes, a type of glial cell, to these operations is poorly documented. r Here we found that optogenetic activation of astrocytes in the vicinity of layer 5 in the mouse primary visual cortex induces spiking in local pyramidal neurons through Nav1.6 ion channels and prolongs the responses elicited in these neurons by stimulation of their distal inputs in cortical layer 1. r This effect partially involved glutamatergic signalling but relied mostly on the astrocytic calcium-binding protein S100β, which regulates the concentration of calcium in the extracellular space around neurons. r These findings show that astrocytes contribute to the fundamental computational operations of the cortex by acting on the ionic environment of neurons.

Freely Behaving Mice Can Brake and Turn During Optogenetic Stimulation of the Mesencephalic Locomotor Region

“…Coronal brainstem slices were obtained from 15-to 23-days old mice as previously described (Ryczko et al, 2020a). Briefly, mice were anesthetized with isoflurane (0.5-1 ml of isoflurane in a 1.5 L induction chamber) and decapitated with a guillotine.…”

Extracellular S100B alters spontaneous Ca2+fluxes in dopaminergic neurons via L-type voltage gated calcium channels: Implications for Parkinson’s disease

“…Recent studies have shown that exposure to extracellular S100B alters the firing properties of pacemaking neurons (Morquette et al, 2015;Ryczko et al, 2021). Based on these findings, we rationalized that any abnormal increase in extracellular S100B concentrations in the SNc could similarly alter DA neuron function.…”

“…Recent studies show that secreted S100B can buffer extracellular Ca 2+ , thereby altering the function of Ca 2+ sensitive K + channels in pacemaking neurons of the trigeminal ganglion and the cortex (Morquette et al, 2015;Ryczko et al, 2021). Given the precedence for a mechanism by which extracellular S100B can modulate neuronal function in multiple brain regions, we sought to determine the extent to which extracellular S100B exposure alters the activity of DA neurons.…”

“…Among the many proteins that are upregulated in reactive astrocytes, S100B is of particular interest in the context of PD because of its potential to initiate pathological processes in DA neurons during early stage PD. Indeed, extracellular S100B has been shown to alter neuronal activity in multiple brain regions (Morquette et al, 2015;Ryczko et al, 2021), and extracellularly secreted S100B from astrocytes accelerates neurodegeneration by engaging receptor for advanced glycation endproducts (RAGE)-mediated pro-inflammatory pathways on astrocytes and microglia (Hofmann et al, 1999;Huttunen et al, 2000;Riuzzi, Sorci, Beccafico, & Donato, 2012). In addition to signaling through RAGE receptors, S100B and the S100 family of proteins interact intracellularly with several ion channels and receptors expressed in neurons, and these interactions result in significant biological effects such as increased neurotropism or the modulation of neuronal excitability (Hermann, Donato, Weiger, & Chazin, 2012).…”

Astrocytes control the spiking of mouse visual cortex layer 5 pyramidal neurons

“…Despite the wealth of literature available on how glia support neuronal functions, there are still substantial gaps in our understanding of how stimulated astrocytes regulate information processing of neurons at the cellular level. In a recent article published in The Journal of Physiology, Ryczko et al (2021) provide evidence that activation of astrocytes regulates the firing of layer 5 pyramidal neurons (L5PNs) by controlling extracellular Ca 2+ levels via releasing the Ca 2+ binding protein S100β.…”