Contribution of astrocytic glutamate and GABA uptake to corticostriatal information processing

Non-technical summary The striatum is a part of the basal ganglia that receives input from the cerebral cortex, extracts relevant information from background noise and relays that information to other parts of the basal ganglia. It is largely composed of nerve cells known as medium-sized spiny neurons (MSNs), and neurons from the cerebral cortex make synaptic connections with them. This study investigates the function of astrocytes at this synaptic connection, where their role is to remove the neurotransmitters glutamate and GABA that spills out from the synaptic cleft. It appears that astrocytes, via the uptake of neurotransmitters, increase the strength of filtering operated by MSNs.The astrocytes, active elements of the tripartite synapse, remove most of the neurotransmitter that spills over the synaptic cleft. Neurotransmitter uptake operated by astrocytes contributes to the strength and timing of synaptic inputs. The striatum, the main input nucleus of basal ganglia, extracts pertinent cortical signals from the background noise and relays cortical information toward basal ganglia output structures. We investigated the role of striatal astrocytic uptake in the shaping of corticostriatal transmission. We performed dual patch-clamp recordings of striatal output neuron (the medium-sized spiny neurons, MSNs)-astrocyte pairs while stimulating the somatosensory cortex. Cortical activity evoked robust synaptically activated transporter-mediated currents (STCs) in 78% of the recorded astrocytes. STCs originated equally from the activities of glutamate transporters and GABA transporters (GATs). Astrocytic STCs reflected here a presynaptic release of neurotransmitters. STCs displayed a large magnitude associated with fast kinetics, denoting an efficient neurotransmitter clearance at the corticostriatal pathway. Inhibition of glutamate transporters type-1 (GLT-1) and GATs decreased the corticostriatal synaptic transmission, through, respectively, desensitization of AMPA receptors and activation of GABA(A) receptor. STCs displayed a bidirectional short-term plasticity (facilitation for paired-pulse intervals less than 100 ms and depression up to 1 s). We report a genuine facilitation of STCs for high-frequency cortical activity, which could strengthen the detection properties of cortical activity operated by MSNs. MSN EPSCs showed a triphasic short-term plasticity, which was modified by the blockade of GLT-1 or GATs. We show here that neurotransmitter uptake by astrocytes plays a key role in the corticostriatal information processing.