Abstract
The majority of synaptic activity in the brain consists of glutamatergic transmission, and there are numerous mechanisms, both intra- and inter-cellular that regulate this excitatory synaptic activity. Importantly, uptake of glutamate plays an important role and a reduced level of astrocytic glutamate transporters affect the normally balanced neurotransmission and is observed in many mental disorders. However, reduced glutamate uptake affects many different synaptic mechanisms in the astrocyte as well as in the neuron, and the effects are challenging to delineate. Combining electrophysiological recordings from neurons and astrocytes as well as extracellular glutamate recordings in rat hippocampal slices, we confirmed previous work showing that synaptic stimulation induces a long-lasting depolarization of the astrocytic membrane that is dependent on inward-rectifier potassium channels. We further showed that when glutamate transporters are blocked, this astrocytic depolarization is greatly enhanced although synaptic responses are reduced. We propose that increasing the levels of synaptic glutamate through blocking glutamate transporters reduces the AMPA-mediated synaptic response while the NMDA receptor current increases, contributing to a rise in extracellular K+ leading to enhanced astrocytic depolarization.
Highlights
Glutamate uptake is a key component in the regulation of excitatory synaptic strength
These results suggest that astrocytes respond to synaptic activity with a slow depolarization mediated by an increase in extracellular K+ triggered by synaptic activity
We show that astrocytes in the hippocampus depolarize upon synaptic stimulation
Summary
Glutamate uptake is a key component in the regulation of excitatory synaptic strength. In the central nervous system the astrocytic excitatory amino acid transporters 1 and 2 (EAAT-1 and 2) are responsible for the majority of glutamate uptake (Bergles and Jahr, 1998), and the neuronal transporters EAAT 3–5 contribute to a lesser extent (Rose et al, 2018). Enhanced Astrocyte Membrane Depolarization receptors as well as presynaptic metabotropic glutamate receptors (Potier et al, 2010), increasing postsynaptic excitation (Tong and Jahr, 1994; Arnth-Jensen et al, 2002) and eventually to excitotoxicity. With increased knowledge about the very tight synapse-astrocyte interaction, it is becoming clear that a pathological increase in glutamate affects the neuronal activity in more complex ways than by inducing excessive increase in activity and excitotoxicity (Goncalves-Ribeiro et al, 2019)
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