The many ways astroglial connexins regulate neurotransmission and behavior

Abstract

Astrocytes have emerged as major players in the brain, contributing to many functions such as energy supply, neurotransmission, and behavior. They accomplish these functions in part via their capacity to form widespread intercellular networks and to release neuroactive factors, which can modulate neurotransmission at different levels, from individual synapses to neuronal networks. The extensive network communication of astrocytes is primarily mediated by gap junction channels composed of two connexins, Cx30 and Cx43, which present distinct temporal and spatial expression patterns. Yet, astroglial connexins are also involved in direct exchange with the extracellular space via hemichannels, as well as in adhesion and signaling processes via unconventional nonchannel functions. Accumulating evidence indicate that astrocytes modulate neurotransmission and behavior through these diverse connexin functions. We here review the many ways astroglial connexins regulate neuronal activity from the molecular level to behavior.

Brainstem astrocytes control homeostatic regulation of caloric intake

“…The current study used chemogenetic approaches, both in vivo and in vitro , to study the effects of DMV astrocyte inhibition, an approach that is not without controversy (Shen et al., 2021), given chemogenetic inhibition may have bidirectional effects on astrocytes, with previous studies showing either an increase (Durkee et al., 2019), an attenuation (Kim et al., 2021), or no change (Van Den Herrewegen et al., 2021) in astrocyte calcium transients. There is notable diversity in the type and time course of calcium responses of astrocytes that are mediated via distinct mechanisms, however, (Khakh & Sofroniew, 2015; Paniccia et al., 2022) and astrocyte activity and gliotransmission may be modulated by additional mechanisms, including alterations in gap junctions, transporters and ion channels (Mazaud et al., 2021; Shen et al., 2021).…”

Connexins Signatures of the Neurovascular Unit and Their Physio-Pathological Functions

“…Astrocytic end feet are connected by GJs composed of Cx43 and Cx30 both temporally and spatially expressed [ 39 , 56 , 57 ]. The consequential homo-cellular (i.e., astrocyte–astrocyte) or hetero-cellular communication represents one of the crucial interaction checkpoints available to modulate NVU functions and CNS homeostasis [ 58 ].…”

“…The roles of Cx30 and Cx43 are likewise evident in the tripartite synapse, where they influence synaptic activity by regulating presynaptic glutamate levels and its transport [ 56 , 65 , 66 , 67 ]. Cx43 is one of the most studied and abundant Cxs; it is widely expressed by glial cells [ 68 , 69 ].…”

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes

“…In most conditions, astrocyte dysfunction is accompanied by changes in the expression of ion channels, neurotransmitter transporters, membrane receptors, or intracellular proteins 65 . Astrocyte gap junctions also control neuronal transmission and behavior 66 . However, we did not find evidence of defective gap junction assembly or abnormal expression of GJA1 in DMSXL astrocytes.…”