Non-Hebbian Synaptic Plasticity Induced by Repetitive Postsynaptic Action Potentials

Abstract

Modern theories on memory storage have mainly focused on Hebbian long-term potentiation (LTP), which requires coincident activation of presynaptic and postsynaptic neurons for its induction. In addition to Hebbian LTP, the roles of non-Hebbian plasticity have also been predicted by some neuronal network models. However, still only a few pieces of evidence have been presented for the presence of such plasticity. In this study, we show in mouse hippocampal slices that LTP can be induced by postsynaptic repetitive depolarization alone in the absence of presynaptic inputs. The induction was dependent on voltage-dependent calcium channels instead of NMDA receptors (NMDARs), whereas the expression mechanism was shared with conventional NMDAR-dependent LTP. During the potentiation, the amplitude of spontaneous EPSCs was increased, suggesting a novel neuron-wide nature of this form of LTP. Furthermore, we also successfully induced LTP with trains of action potentials, which supported the possible existence of depolarizing pulse-induced LTP in vivo. Based on these findings, we suggest a model in which neuron-wide LTP works in concert with synapse-specific Hebbian plasticity to help information processing in memory formation.

Conditional ablation of neuroligin-1 in CA1 pyramidal neurons blocks LTP by a cell-autonomous NMDA receptor-independent mechanism

“…In this protocol, NMDARs are blocked pharmacologically by high concentrations of AP5 (50 μM). Potentiation of AMPAR-EPSCs is then elicited by repetitive activation of voltage-gated Ca 2+ -channels (VGCCs), primarily L-type Ca 2+ -channels 22,32,33 4 (Fig. S6).…”

“…To induce NMDAR-dependent LTP, after collecting a 5–10 min baseline 2 trains of high frequency stimulation (100 Hz, 1s) separated by 20 s were delivered while clamping the postsynaptic cell at 0 mV 20 . To induce NMDAR-independent LTP 22 , twenty postsynaptic depolarization pulses (80 mV, 1 s separated by 6 s) were applied to cells clamped at −70 mV. 5 μM Bay K8644 (an L-type calcium channel activator) and 50 μM APV were included in the ACSF.…”

Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits

“…In addition, the Nlgn1 deletion completely blocked postsynaptic, NMDAR-dependent LTP. Even though called NMDAR-dependent LTP, this type of LTP is also efficiently induced by increases in postsynaptic Ca 2+ in the absence of NMDAR activation (Kullmann et al, 1992; Weisskopf et al, 1999; Kato et al, 2009). The Nlgn1 deletion also blocked LTP induced by this NMDAR-independent protocol, demonstrating that Nlgn1 performs independent functions in maintaining normal NMDAR-mediated responses and in enabling LTP (Jiang et al, 2016), with the function of Nlgn1 in LTP possibly related to that of Nrxn3 in LTP (Aoto et al, 2013).…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…The most studied forms of neuroplasticity are NMDAR-dependent LTP and LTD, with the NMDARs providing the major pathway for Ca 2+ influx (Huang and Kandel, 1996). There is also NMDAR-independent LTP and LTD, in which VGCC (Kato et al, 2009) or GluA2 subunit-lacking AMPARs provide the Ca 2+ influx triggering induction. In the early phases of LTP, elevated Ca 2+ triggers persistent activation of protein kinases including PKA, Ca 2+ /calmodulin kinase II (CaMKII), and protein kinase C (PKC).…”