Uptake of glutamate by perisynaptic astrocyte processes limits glutamate escape into extrasynaptic space and thus determines the spatial fidelity of synaptic transmission. Importantly, the coverage of synapses by perisynaptic astrocyte processes can vary strongly between nearby synapses. However, the factors that determine local astrocytic coverage of synapses and the functional significance of variable coverage remain largely unknown. Interestingly, expansion microscopy of dendritic spines of pyramidal cells in the hippocampal CA1 region and adjacent astrocyte processes revealed a negative correlation between the spine size and the abundance of perisynaptic glutamate transporters. Functional tests using two-photon excitation imaging of extracellular glutamate and intracellular Ca2+ provided evidence for more efficient glutamate uptake at smaller spines. This indicates that the spine size may determine the efficiency of local glutamate uptake and thus the spatial precision of synaptic transmission. It also implies that astrocytic coverage of spines should decrease after induction of spine growth. The latter is a common observation after induction of synaptic long-term potentiation (LTP). We provide evidence that LTP induction indeed withdraws astrocyte processes from synapses. On the functional level, this withdrawal led to increased escape of glutamate into extrasynaptic space (detected by optical glutamate sensors). In addition, increased glutamate spill-over onto high-affinity N-methyl-D-aspartate receptors at inactive synapses was observed after LTP induction. Our observations indicate that spine size and synaptic plasticity dynamically determine the spatial configuration of synapses and perisynaptic astrocyte processes. On the functional level and as a consequence, glutamate uptake is less efficient at larger postsynaptic spines and after LTP induction, which increases the probability of glutamate to escape active synapses and to invade neighbouring synapses. FINANCIAL SUPPORT: NRW-Rückkehrerprogramm, HFSP, DFG.
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.