Glutamate is required for depression but not potentiation of long-term presynaptic function.

Zahid Padamsey,Nigel Emptage,Rudi Tong

doi:10.7554/elife.29688

Abstract

Hebbian plasticity is thought to require glutamate signalling. We show this is not the case for hippocampal presynaptic long-term potentiation (LTPpre), which is expressed as an increase in transmitter release probability (Pr). We find that LTPpre can be induced by pairing pre- and postsynaptic spiking in the absence of glutamate signalling. LTPpre induction involves a non-canonical mechanism of retrograde nitric oxide signalling, which is triggered by Ca2+ influx from L-type voltage-gated Ca2+ channels, not postsynaptic NMDA receptors (NMDARs), and does not require glutamate release. When glutamate release occurs, it decreases Pr by activating presynaptic NMDARs, and promotes presynaptic long-term depression. Net changes in Pr, therefore, depend on two opposing factors: (1) Hebbian activity, which increases Pr, and (2) glutamate release, which decreases Pr. Accordingly, release failures during Hebbian activity promote LTPpre induction. Our findings reveal a novel framework of presynaptic plasticity that radically differs from traditional models of postsynaptic plasticity.

Highlights

Learning and memory are thought to require synaptic plasticity, which refers to the capacity for synaptic connections in the brain to change with experience
Baseline excitatory postsynaptic potentials (EPSPs) recordings were kept short (5 min) to minimize dialysis as we found that longer baseline recordings prevented LTPpre induction
We found that this pairing protocol produced robust and reliable LTP, which had a presynaptic component of expression, as assessed by a decrease in the paired pulse ratio (PPR) (DPPR: À0.39 ± 0.15; n = 6 cells; vs 0: p

Summary

Introduction

Learning and memory are thought to require synaptic plasticity, which refers to the capacity for synaptic connections in the brain to change with experience. Postsynaptic NMDA receptor (NMDAR) activation is believed to be important for both pre- and postsynaptic forms of plasticity (Bliss and Collingridge, 2013; Luscher and Malenka, 2012). In the case of LTPpre induction, it is traditionally thought that Ca2+ influx through postsynaptic NMDARs triggers the synthesis and release of a retrograde signal, most likely nitric oxide (NO), which in turn triggers increases in Pr (Padamsey and Emptage, 2014; Garthwaite and Boulton, 1995) (though other forms of presynaptic plasticity exist [Yang and Calakos, 2013; Castillo, 2012]).

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