Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

“…Original reports of DSI concerned stellate/basket cell inputs onto cerebellar Purkinje cells (Llano et al, 1991;Vincent et al, 1992), as well as GABAergic inputs onto CA1 pyramidal cells (Pitler & Alger, 1992;Pitler & Alger, 1994;Figure 1a). DSE was found at parallel and climbing fiber inputs of Purkinje cells (Kreitzer & Regehr, 2001a) and at glutamatergic inputs onto CA1 pyramidal cells (Ohno-Shosaku et al, 2002b).…”

“…It was quickly recognized that the calcium concentration rise that follows postsynaptic depolarization serves as a signal for DSI/DSE. Three lines of evidence indicate that this increase in intracellular calcium is both a necessary and a sufficient condition for induction: (1) blockers of calcium entry block DSI (Llano et al, 1991;Lenz et al, 1998); (2) postsynaptic application of calcium chelating agents like EGTA and/or BAPTA prevent DSI/DSE (Pitler & Alger, 1992;Glitsch et al, 2000;Kreitzer & Regehr, 2001a;Ohno-Shosaku et al, 2002a); (3) postsynaptic calcium uncaging is able to trigger synaptic depression (Wang & Zucker, 2000;.…”

“…On the left, bars show the amount of DSI inhibition by two distinct CB1R antagonists, AM251 and SR141716, with sample traces for control DSI and DSI in antagonist depicted above (from ). rapidly established, on the basis of the following observations: (1) The postsynaptic sensitivity to GABA, as measured either by the amplitude of miniature synaptic currents, or by that of responses to applications of exogenous neurotransmitter, is not modified during DSI (Llano et al, 1991;Pitler & Alger, 1992). (2) The frequency, but not the amplitude of miniature inhibitory postsynaptic currents (mIPSCs) decreases during cerebellar DSI (Llano et al, 1991;Glitsch et al, 1996;Figure 2c).…”

“…rapidly established, on the basis of the following observations: (1) The postsynaptic sensitivity to GABA, as measured either by the amplitude of miniature synaptic currents, or by that of responses to applications of exogenous neurotransmitter, is not modified during DSI (Llano et al, 1991;Pitler & Alger, 1992). (2) The frequency, but not the amplitude of miniature inhibitory postsynaptic currents (mIPSCs) decreases during cerebellar DSI (Llano et al, 1991;Glitsch et al, 1996;Figure 2c). (3) During DSI, the percentage of synaptic failures increases (Vincent et al, 1992;Alger et al, 1996;Diana & Marty, 2003), and so does the paired pulse ratio during DSI and DSE (Ohno-Shosaku et al, 1998;Ohno-Shosaku et al, 2002b;Yoshida et al, 2002;Diana & Marty, 2003;Trettel & Levine, 2003; but see Alger et al, 1996;Varma et al, 2002).…”

“…In view of the findings that a postsynaptic signal, a calcium concentration rise, was the trigger of DSI, and that a presynaptic modification, a reduction of transmitter release, was the end effect, the existence of a retrograde messenger was soon proposed (Llano et al, 1991). Early studies proposed that glutamate was released postsynaptically, and that it activated presynaptic metabotropic glutamate receptors (mGluRs) of group II (in the cerebellum: Glitsch et al, 1996) or of group I (in the hippocampus: Morishita et al, 1998).…”