Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

Abstract

The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD) in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex.

Protein phosphatases 1 and 2A are both required for long‐term depression and associated dephosphorylation of cAMP response element binding protein in hippocampal area CA1 in vivo

“…Moreover, whereas PPS caused a significant depression of the pEPSP in the presence of vehicle solution (5 min before PPS vs. 37 min after PPS, p < 0.01), it failed to do so in the presence of okadaic acid ( p > 0.2). The failure of LTD development in the presence of okadaic acid, combined with our previous demonstration that the induction of LTD by PPS is dependent on NMDA receptor activation (Thiels et al, 1998), is consistent with previous observations of an effect of this inhibitor on NMDA receptor-dependent LTD in area CA1 or the entorhinal cortex (Xiao et al, 1995; Jouvenceau et al, 2003; Kourrich et al, 2008). Furthermore, it suggests that either one or both of the okadaic acid-sensitive protein phosphatases are necessary for the development of NMDA receptor-dependent LTD.…”

“…A number of studies showed that the PP1 and PP2A inhibitor okadaic acid disrupts NMDA receptor-dependent LTD at glutamatergic synapses in hippocampus as well as elsewhere in brain (Mulkey et al, 1993; Kirkwood & Bear, 1994; Morishita et al, 2001; Jouvenceau et al, 2003; Belmeguenai & Hansel, 2005; Kourrich et al, 2008), implicating one or both of these protein phosphatases in activity-dependent modification of synaptic strength. Here we sought to determine the role of each of these two protein phosphatases individually to NMDA receptor-dependent LTD in area CA1 in vivo (Thiels et al, 1998), taking advantage of specific inhibitors of PP1 and PP2A, respectively.…”

Presynaptic Spike Timing-Dependent Long-Term Depression in the Mouse Hippocampus

“…10 A , C ). FK506 was active when loaded into the postsynaptic neurons as loading the same concentration of FK506 into neurons of layer 2 of the medial entorhinal cortex completely prevented LTD in synaptic input from layer 1 (not shown), as previously reported ( Kourrich et al 2008 ), indicating that presynaptic calcineurin is involved in the induction of hippocampal t-LTD..

Figure 10. Presynaptic calcineurin is involved in t-LTD at CA3-CA1 synapses.

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Treatment with direct-current stimulation against cingulate seizure-like activity induced by 4-aminopyridine and bicuculline in an in vitro mouse model

“…When okadaic acid was applied internally, it produces a slowly developing attenuation in response to 0.05 Hz test pulse. When the test pulse is doubled to 0.1 Hz, the attenuation is faster and occludes subsequent LTD. Attenuation of evoked responses by okadaic acid was also shown in other studies (Kourrich, et al, 2008). Previous studies also showed that application of non-selective phosphatase inhibitors calyculin A or microcystin-LR attenuated Purkinje EPSC (Ajima and Ito, 1995).…”