Receptor saturation controls short-term synaptic plasticity at corticothalamic synapses

Abstract

Sun Y-G, Beierlein M. Receptor saturation controls short-term synaptic plasticity at corticothalamic synapses. J Neurophysiol 105: 2319 -2329, 2011. First published February 16, 2011 doi:10.1152/jn.00942.2010.-Glutamatergic synapses of layer 6 corticothalamic (CT) neurons form a major excitatory input onto thalamic relay cells, allowing neocortex to continuously control sensory information processing in thalamic circuits. CT synapses display both short-and long-term forms of use-dependent synaptic enhancement, mediated at least in part by increases in the probability of transmitter release. At some synapses, such increases in release probability are accompanied by a higher degree of multivesicular release (MVR) and larger glutamate transients at individual release sites, resulting in the saturation of postsynaptic receptors. The extent to which MVR and postsynaptic saturation interact and control shortterm plasticity at CT synapses is not known. Here we examined two distinct presynaptic forms of short-term enhancement, facilitation and augmentation, at CT synapses contacting relay neurons in the ventrobasal nucleus of the mouse thalamus. We found that, in the presence of the low-affinity antagonist ␥-D-glutamylglycine, to relieve postsynaptic DL-␣-amino-3-hydroxy-5-methylisox azole-propionic acid (AMPA) receptor saturation, the magnitude of facilitation and augmentation increased. Whereas receptor saturation was prominent for both AMPA and N-methyl-D-aspartate receptors, desensitization of AMPA receptors did not significantly alter short-term plasticity. Our results suggest that at CT synapses the activity-dependent increase in synaptic strength is controlled by postsynaptic receptor saturation.

Activation of Extrasynaptic NMDARs at Individual Parallel Fiber–Molecular Layer Interneuron Synapses in Cerebellum

“…Photomultipliers (H8224P-40 or H10770PA-40; Hamamatsu) collected red and green emissions in both epifluorescence and transfluorescence pathways (Christie and Jahr, 2008). For the experiments presented in Figure 9, data were acquired using ScanImage software (Pologruto et al, 2003). Line scans were performed at 500 Hz and fluorescence changes were calculated by subtracting the baseline green signal followed by normalization to the red signal (⌬G/R).…”

“…We used MVA to determine whether univesicular eEPSCs could be easily modeled by a simple, single release site synapse (Clements, 2003;Silver, 2003;Foster and Regehr, 2004;Saviane and Silver, 2007). To maximize the number of release conditions, we performed MVA on the three eEPSCs in the train in the presence and absence of baclofen.…”

“…These two results, lower than expected Pr but higher potency of successes, are consistent if the Pr of a second vesicle is contingent on the release of the first. Seventh, several previous papers have reported that PF synapses, on both MLIs and PCs, can release multiple vesicles per AP (Foster et al, 2005;Rancillac and Barbara, 2005;Bender et al, 2009).…”

“…Granule cells can respond to mossy fiber input with bursts of action potentials (APs) at frequencies of several hundred hertz (Chadderton et al, 2004;Jörntell and Ekerot, 2006) and their synapses onto both Purkinje cells (PCs) and MLIs exhibit frequency facilitation (Konnerth et al, 1990;Perkel et al, 1990;Atluri and Regehr, 1996). PF boutons have an average of seven vesicles docked at each PF-PC active zone (Xu-Friedman et al, 2001), the presumed source for multivesicular release (MVR) (Foster et al, 2005;Rancillac and Barbara, 2005;Bender et al, 2009;Valera et al, 2012).…”

“…PF boutons have an average of seven vesicles docked at each PF-PC active zone (Xu-Friedman et al, 2001), the presumed source for multivesicular release (MVR) (Foster et al, 2005;Rancillac and Barbara, 2005;Bender et al, 2009;Valera et al, 2012). In addition to MVR, bursts of PF APs cause asynchronous vesicular release (Atluri and Regehr, 1998;Chen and Regehr, 1999).…”