How do astrocytes shape synaptic transmission? Insights from electrophysiology

Abstract

A major breakthrough in neuroscience has been the realization in the last decades that the dogmatic view of astroglial cells as being merely fostering and buffering elements of the nervous system is simplistic. A wealth of investigations now shows that astrocytes actually participate in the control of synaptic transmission in an active manner. This was first hinted by the intimate contacts glial processes make with neurons, particularly at the synaptic level, and evidenced using electrophysiological and calcium imaging techniques. Calcium imaging has provided critical evidence demonstrating that astrocytic regulation of synaptic efficacy is not a passive phenomenon. However, given that cellular activation is not only represented by calcium signaling, it is also crucial to assess concomitant mechanisms. We and others have used electrophysiological techniques to simultaneously record neuronal and astrocytic activity, thus enabling the study of multiple ionic currents and in depth investigation of neuro-glial dialogues. In the current review, we focus on the input such approach has provided in the understanding of astrocyte-neuron interactions underlying control of synaptic efficacy.

Dissecting tripartite synapses with STED microscopy

“…In order to carry out our analysis of the tripartite synapse at a mature stage (as opposed to during development), we checked the electrophysiological properties of astrocytes. After five weeks in culture, astrocytes in the stratum radiatum of CA1 appear to be electrophysiologically similar to those in acute slices (figure 3a) [16]. Astrocytes are characterized by (i) hyperpolarized resting membrane potential (%280 mV), (ii) a low input resistance (%4-20 MV), (iii) a linear current -voltage relationship in voltage clamp as well as (iv) absence of spiking behaviour ( figure 3a).…”

“…Astrocytes surely possess powerful mechanisms to influence synaptic function by way of: (i) the clearance of glutamate from the synaptic space by glutamate transporters, such as GLT-1, which are thought to be expressed at extremely high density (more than 5000 mm 22 ) at synapses [15]; (ii) the buffering of potassium ions in the extracellular environment [16]; (iii) the release of a panoply of gliotransmitters; and (iv) physically shaping the diffusional space of the synapse. Given the apposition of astrocytic and neuronal membranes at synapses [17,18], with hyperthin astrocytic processes possibly invading the synaptic cleft [19], a major influence of astrocytes on synapses is easily conceivable.…”

Glial Cell Development and Function in Zebrafish

“…This raises the possibility that some radial glia (which can directly transform into astrocytes at late stages of mammalian nervous system development [Voigt 1989;Barry and McDermott 2005]) become specialized in anamniotes to subserve many of the functions of differentiated astrocytes. Over the past decade, the number of functions associated with mammalian astrocytes has increased greatly, with evidence of their involvement in processes as diverse as responding to neuronal injury (Cregg et al 2014), providing metabolic support to neurons (Bouzier-Sore and Pellerin 2013), maintaining ionic and osmotic balance and integrity of the blood brain barrier, regulating blood flow (Attwell et al 2010), regulating the formation (Eroglu and Barres 2010;Allen et al 2012), pruning (Chung et al 2013c), and function of synapses (Dallérac et al 2013), and even regulating learning and memory, where transplantation of human astrocytes into rodents enhanced synaptic plasticity (Han et al 2013). Detailed discussion of the many roles of astrocytes is beyond the scope of this review, but we briefly consider the evidence that radial glia in zebrafish may serve some specialized roles of astrocytes in mammals.…”

Imaging and monitoring astrocytes in health and disease

“…This method is based on the analysis by conventional microscopy of acutely-dissociated astrocytes from the mouse brain. Dallérac et al (2013) discuss how astrocytes are not silent in the brain and how studying astrocytes by electrophysiological recordings provides insight into their complex communication with neurons at the synapse. In their Original research article, Kabaso et al (2013) use electrophysiology, this time combined with modeling, to describe the mechanical properties of vesicular release from astrocytes.…”