Polarity of Long-Term Synaptic Gain Change Is Related to Postsynaptic Spike Firing at a Cerebellar Inhibitory Synapse

Abstract

Long-term potentiation and depression (LTP and LTD) in excitatory synapses can coexist, the former being triggered by stimuli that produce strong postsynaptic excitation and the latter by stimuli that produce weaker postsynaptic excitation. It has not been determined whether these properties also apply to LTP and LTD in the inhibitory synapses between Purkinje neurons and the neurons of the deep cerebellar nuclei (DCN), a site that has been implicated in certain types of motor learning. DCN cells exhibit a prominent rebound depolarization (RD) and associated spike burst upon release from hyperpolarization. In these cells, LTP can be elicited by short, high-frequency trains of inhibitory postsynaptic potentials (IPSPs), which reliably evoke an RD. LTD is induced if the same protocol is applied with conditions where the amount of postsynaptic excitation is reduced. The polarity of the change in synaptic strength is correlated with the amount of RD-evoked spike firing during the induction protocol. Thus, some important computational principles that govern the induction of use-dependent change in excitatory synaptic efficacy also apply to inhibitory synapses.

Cerebellar cortical inhibition and classical eyeblink conditioning

“…1 A, trace 2). The IPSPs were mediated by GABA A receptors, and the EPSPs by ionotropic glutamate receptors because they were blocked by PTX and kynurenic acid, respectively (data not shown), as has been shown (15). DNNs (n ϭ 3) also exhibited spontaneous GABAergic synaptic currents (Fig.…”

“…For example, in classical eyeblink conditioning, mossy fibers (mf) and climbing fibers (cf) are thought to convey conditioned stimulus (CS) and unconditioned stimulus (US) signals, respectively, to both the cerebellar cortex and the deep nuclei. Various types of synaptic plasticity have been demonstrated in these regions, including parallel fiberPurkinje cell long-term depression (pf-PC LTD) (11,12) and long-term potentiation (pf-PC LTP) (13), pf-PC ␥-aminobutyric acid (GABA)-transmitting rebound potentiation (14), PC-deep nuclear neuron (DNN) LTD (15,16), and LTP of extracellular responses in the cerebellar deep nuclei (17). These different types of plasticity may be involved in supporting learning in both the cerebellar cortex and deep nuclei (10,18,19).…”

T-type calcium channels in synaptic plasticity

“…Indeed, following the first reports describing the generation of low-threshold 41 The contribution of the T-type current induced depolarization to the induction of long-term synaptic plasticity is fairly well established. However, to what extent does the rise in postsynaptic Ca 2C necessary to trigger synaptic plasticity specifically occur through T-type channels?…”

“…Whereas LTP were induced in conditions where pronounced rebound depolarization elicited significant spiking (>5 action potentials), LTD required rebound depolarizations that had little or no spiking. 41,75 Although activation of high-voltage Ca 2C channels by action potentials can explain why a strong rebound firing is required to trigger LTP, the exact biochemical mechanisms coupling the rebound depolarization to either LTP or LTD of IPSPs are still unknown. These data highlight the fact that either form of plasticity can be evoked depending on the pattern of LTS activation.…”

Interaction of Calcineurin and Type-A GABA Receptor γ2Subunits Produces Long-Term Depression at CA1 Inhibitory Synapses

“…These coordinately regulated bidirectional changes of the excitatory and inhibitory synaptic strength are considered to be a cellular model of learning and memory (Bliss and Collingridge, 1993;Paulsen and Moser, 1998). Although we now know a great deal about the molecular steps contributing to the induction of LTP at excitatory synapses (Malenka and Nicoll, 1999;Malinow et al, 2000;Ali and Salter, 2001;Lisman and Zhabotinsky, 2001), the molecular mechanisms underlying the induction of LTD at CA1 individual inhibitory synapses have not been identified (Abraham et al, 1987;Thompson and Gahwiler, 1989;Thompson, 1994;Aizenman et al, 1998).…”