A Snapshot seminar hosted by the School of Physiology, Pharmacology and Neuroscience

AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and have a central role in learning and memory. AMPAR channels can be composed of four subunits (GluA1-4) with different combinations and the subunit composition can affect channel properties, receptor trafficking and interaction with other associated proteins. Synaptic plasticity involving changes in the AMPAR numbers and subunit composition has been reported in various in vitro preparations combined with artificial stimulation protocols. However, what happens in vivo by physiological learning has been only sparsely demonstrated. Using the high sensitivity SDS-digested freeze-fracture replica labeling (SDS-FRL) for electron microscopy, we investigated the number, density, and localization patterns of AMPAR subunits, GluA1, GluA2, GluA3, and panAMPAR (GluA1-3) in the CA1 area of the mouse hippocampus. In naïve animals, we have found that the immunogold labeling for all of these subunits in the postsynaptic sites was highest in stratum radiatum and lowest in stratum lacunosum-moleculare. The intra-synaptic labeling density for GluA1 and GluA2 was higher in the periphery than the center of synapses, whereas GluA3 was more concentrated in the center. In the extrasynaptic sites, we found high densities of GluA1 and GluA2, showing about 10% of synaptic densities, while the ratio of extrasynaptic GluA3 was significantly lower. The extrasynaptic densities for all the subunits showed a gradual increase from the pyramidal cell soma towards the distal part of stratum radiatum. By combining inhibitory avoidance task with SDS-FRL, we have revealed an increase in synaptic density and re-organization specific to GluA1 in the CA1 area. The intra-synaptic GluA1 distribution changed to the center-concentrated pattern 30 min after the conditioning. Furthermore, this type of synaptic plasticity occurred selectively in stratum radiatum but not stratum oriens, and selectively in the CA1 sub-region proximal to the CA2 area. These findings contribute to our understanding of how specific hippocampal sub-regions and AMPA receptor subunits are involved in physiological learning.

Prof. Ryuichi Shigemoto (https://ist.ac.at/en/research/shigemoto-group/)

Host: Elek Molnar

Location: https://bristol-ac-uk.zoom.us/j/4798119105?pwd=MlZRZEt6aWhQb0NYT2pXd3N5aVRvQT09