Astrocytes Are Endogenous Regulators of Basal Transmission at Central Synapses

Abstract

Basal synaptic transmission involves the release of neurotransmitters at individual synapses in response to a single action potential. Recent discoveries show that astrocytes modulate the activity of neuronal networks upon sustained and intense synaptic activity. However, their ability to regulate basal synaptic transmission remains ill defined and controversial. Here, we show that astrocytes in the hippocampal CA1 region detect synaptic activity induced by single-synaptic stimulation. Astrocyte activation occurs at functional compartments found along astrocytic processes and involves metabotropic glutamate subtype 5 receptors. In response, astrocytes increase basal synaptic transmission, as revealed by the blockade of their activity with a Ca(2+) chelator. Astrocytic modulation of basal synaptic transmission is mediated by the release of purines and the activation of presynaptic A(2A) receptors by adenosine. Our work uncovers an essential role for astrocytes in the regulation of elementary synaptic communication and provides insight into fundamental aspects of brain function.

Rapid stimulus-evoked astrocyte Ca 2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo

“…The majority of the fast, high-frequency signals could be identified only after superposition of data points recorded during a stimulation train, which might explain why fast astrocytic Ca 2+ signals have so seldom been reported in vivo (9) and emphasizes the relevance of the method of analysis applied here. Our results are consistent with work in hippocampal slices (16,17). In somatosensory cortex, previous findings suggested that only 5% of astrocyte somas had fast Ca 2+ responses in vivo (9).…”

“…Furthermore, uncaging of Ca 2+ in astrocytes triggers vascular responses in brain slices through specific Ca 2+ -dependent pathways with a protracted time course (14, 15). More recently, stimulation of single presynaptic neurons in hippocampal slices was shown to evoke fast, brief, local Ca 2+ elevations in astrocytic processes that were essential for local synaptic functioning in the adult brain (16,17). This work prompted us to reexamine the characteristics of fast, brief astrocytic Ca 2+ signals in vivo with special regard to neurovascular coupling, i.e., the association between local increases in neural activity and the concomitant rise in local blood flow, which constitutes the physiological basis for functional neuroimaging.…”

Pannexin-1-mediated ATP release from area CA3 drives mGlu5-dependent neuronal oscillations

“…A 2A receptors are present in the hippocampus and respond to astrocytic mGlu5 activation by increasing synaptic strength (Panatier et al, 2011). To establish whether the activation of excitatory A 2A receptors contributed to DHPG-induced bursting we applied ZM 241385 (0.1 µM), a potent A 2A receptor antagonist, and compared DHPG-induced bursting in the presence and absence of ZM 241385 ( Figure 2B).…”

Rapid Genotyping of Animals Followed by Establishing Primary Cultures of Brain Neurons

“…We prefer the last of the three approaches to low-density culture, because the Neurobasal Medium can affect neuronal survival 57 , the astrocytic glial cells will be essential in regulating neuronal functions 8,58 , and the physical contact between neurons and glial cells may be important. The procedures for culturing the mouse and rat glial cells are similar 59,60 , but we have modified them slightly to accommodate for the more rapid in vitro growth of rat vs. mouse glial cells.…”