Differential Expression of Posttetanic Potentiation and Retrograde Signaling Mediate Target-Dependent Short-Term Synaptic Plasticity

Abstract

Short-term synaptic plasticity influences how presynaptic spike patterns control the firing of postsynaptic targets. Here we investigated whether specific mechanisms of short-term plasticity are regulated in a target-dependent manner by comparing synapses made by cerebellar granule cell parallel fibers onto Golgi cells (PF-->GC synapse) and Purkinje cells (PF-->PC synapse). Both synapses exhibited similar facilitation, suggesting that any differential short-term plasticity does not reflect differences in the initial release probability. PF-->PC synapses were highly sensitive to stimulus bursts, which could result in either depression of subsequent responses, mediated by endocannabinoid-dependent retrograde signaling, or enhancement of responses through posttetanic potentiation (PTP). In contrast, stimulus bursts had remarkably little effect on the strength of PF-->GC synapses. Unlike PCs, GCs were unable to regulate their PF synapses by releasing endocannabinoids. Moreover, PTP was reduced at the PF-->GC synapse compared to the PF-->PC synapse. Thus, the target-dependence of PF synapses arises from the differential expression of both retrograde signaling and PTP.

Target Cell-Specific Involvement of Presynaptic Mitochondria in Post-Tetanic Potentiation at Hippocampal Mossy Fiber Synapses

“…Protein kinase C contributes to PTP specifically at MF synapses onto hilar interneuron Previously, activation of PKC has been proposed as underlying mechanisms for PTP at the synapses in hippocampus and in cerebellum (Alle et al, 2001;Brager et al, 2003;Beierlein et al, 2007;Wierda et al, 2007). We studied whether PKC is differentially involved in PTP at MF3 MC and MF3 HI synapses.…”

“…Although mitochondrial contribution to generation of Ca res and PTP has been demonstrated at NMJs (Tang and Zucker, 1997;Garcia-Chacon et al, 2006), there is little evidence for mitochondrial involvement at central synapses (Storozhuk et al, 2005). Instead, activation of protein kinase has been proposed as underlying mechanisms for PTP in hippocampus and cerebellum, suggesting that PTP mechanism at central synapses may be different from that at NMJs (Alle et al, 2001;Brager et al, 2003;Beierlein et al, 2007;Wierda et al, 2007). The evidence accumulated over the last decade supports the view that short-term plasticity from the same axon is different according to the identity of postsynaptic target (for review, see Toth and McBain, 2000).…”

Short-Term Presynaptic Plasticity

“…The linear correlation between EPSC amplitude and Ca res is compatible with a mechanism in which an increase in Ca res of several hundred nanomolar leads to a doubling of synaptic strength. Following tetanic stimulation at some hippocampal and cerebellar synapses, Ca res decays more rapidly than does PTP, suggesting that Ca res may activate a slow biochemical cascade, and the kinetics of this calciumdriven process help to determine the duration of PTP (Regehr et al 1994;Brager et al 2003;Beierlein et al 2007). …”

“…Pharmacological studies implicated protein kinase C (PKC) in PTP at several synapses (Alle et al 2001;Brager et al 2003;Beierlein et al 2007;Korogod et al 2007). However, the involvement of PKC in PTP was uncertain because the selectivity and specificity of PKC activators and inhibitors was called into question (Brose and Rosenmund 2002;Lee et al 2008), and PTP was unaffected by PKC inhibitors at some synapses (Reymann et al 1988a,b;Eliot et al 1994;Lee et al 2008).…”

“…The involvement of calcium-sensitive isoforms suggests that PKC responds to Ca res to produce PTP, possibly by phosphorylating Munc18-1 to alter the effective pool size and the probability of release (Nili et al 2006;Toonen et al 2006;Toonen and Verhage 2007). Munc13, a calciumsensitive presynaptic protein that regulates the priming and probability of release of vesicles, has been shown to influence short-term synaptic plasticity during and following tetanic activation (Brose and Rosenmund 2002;Junge et al 2004;Beierlein et al 2007;Shin et al 2010). It is influenced by many of the pharmacological agents that regulate PKC, and has been proposed as an alternative to PKC as a mediator of PTP and augmentation.…”