1 Receptor saturation controls short - term synaptic plasticity at corticothalamic synapses

Glutamatergic synapses of layer 6 corticothalamic (CT) neurons form a major 28 excitatory input onto thalamic relay cells, allowing neocortex to continuously control sensory 29 information processing in thalamic circuits. CT synapses display both shortand long-term forms 30 of use-dependent synaptic enhancement, mediated at least in part by increases in the probability 31 of transmitter release. At some synapses, such increases in release probability are accompanied by 32 a higher degree of multivesicular release and larger glutamate transients at individual release sites, 33 resulting in the saturation of postsynaptic receptors. The extent to which multivesicular release 34 (MVR) and postsynaptic saturation interact and control short-term plasticity at CT synapses is not 35 known. Here we examined two distinct presynaptic forms of short-term enhancement, facilitation 36 and augmentation, at CT synapses contacting relay neurons in the ventrobasal nucleus of the 37 mouse thalamus. We found that in the presence of the low-affinity antagonist γ-D-glutamylglycine 38 (DGG) to relieve postsynaptic AMPA receptor saturation, the magnitude of facilitation and 39 augmentation increased. Whereas receptor saturation was prominent for both AMPA and NMDA 40 receptors, desensitization of AMPA receptors did not significantly alter short-term plasticity. Our 41 results suggest that at CT synapses the activity-dependent increase in synaptic strength is 42 controlled by postsynaptic receptor saturation. 43 44