Cortical astrocyte N-Methyl-D-Aspartate receptors influence whisker barrel activity and sensory discrimination

Abstract

Cortical astrocytes encode sensory information through their calcium dynamics, but it remains unclear if modulation of astrocyte calcium transients can change somatosensory circuits and behaviour in vivo. Here, we used a novel knockdown approach to selectively reduce astrocyte N-methyl-D-aspartate receptors (NMDAR). We found that these ionotropic receptors contribute to astrocyte Ca2+transients encoding sensory information. This was essential for the optimal processing of sensory information in nearby neurons, since a reduction in astrocyte NMDARs caused circuit dysfunction and impaired neuronal responses to stimulation. This led to sensory discrimination deficits in the animal. Overall, our findings show that astrocytes can rapidly respond to glutamatergic transmission via their NMDAR and these receptors are an important component for astrocyte-neuron interactions that regulate cortical sensory discrimination in vivo.

L-Type Ca2+channels and TRPC3 channels shape brain pericyte Ca2+signaling and hemodynamics throughout the arteriole to capillary networkin vivo

“…To access brain pericytes in mice, in an in vivo setting via two-photon imaging, a chronic cranial window was implanted as described in our previous work (56, 57). The surgery was done in two parts.…”

Active enhancement of synapse driven depolarization of perisynaptic astrocytic processes

“…Next, we examined astrocytic channels with sustained currents activated with potassium or glutamate from the AP. As recent reports imply the functional expression of NMDAR on the astrocyte and at the PAP [14][15][16], we examined the effects of these channels on PAP depolarization. As sub-compartment proteomes of tripartite synapses show a lack of NMDAR [17] as well as many reports contradicting the expression of astrocytic NMDAR [18,19], we hypothesize that these channels are expressed at a much lower density than Kir 4.1 channels, making them difficult to detect with conventional methods.…”

Astrocyte modulation of synaptic plasticity mediated by activity-dependent Sonic hedgehog signaling

“…Astrocytes associate intimately with synapses, comprising the third partner in the tripartite synapse, along with the pre and postsynaptic terminals 1 . They express a large complement of receptors, transporters, and ion channels [2][3][4] , enabling them to monitor and respond to neural activity [5][6][7] and reciprocally regulate synapse function [8][9][10][11][12][13] . This is accomplished through Ca 2+ -mediated gliotransmission 14 as well as activity-dependent changes in astrocyte gene expression.…”

“…They associate intimately with synapses, comprising the third partner in the tripartite synapse, along with the pre and postsynaptic terminals 5 . Astrocytes monitor and respond to neural activity [6][7][8][9] and engage in reciprocal regulation of synapse function [10][11][12][13][14] through a large complement of receptors, transporters, and ion channels embedded within their membranes [15][16][17] . They also exert broad influence on the plasticity of synapses and circuits in development and in learning and memory [18][19][20][21][22] .…”