Gating of NMDA receptor-mediated hippocampal spike timing-dependent potentiation by mGluR5

Jeehyun Kwag,Ole Paulsen

doi:10.1016/j.neuropharm.2012.05.021

Jeehyun Kwag, Ole Paulsen

Open Access

https://doi.org/10.1016/j.neuropharm.2012.05.021

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Abstract

Hippocampal long-term potentiation (LTP) is believed to be important for learning and memory. Experimentally, the pairing of precisely timed pre- and postsynaptic spikes within a time window of ∼10 ms can induce timing-dependent LTP (tLTP), but the requirements for induction of tLTP change with development: in young rodents single postsynaptic spikes are sufficient to induce tLTP, whereas postsynaptic burst firing appears to be required in the adult. However, hippocampal neurons in vivo show theta-modulated single spike activities also in older hippocampus. Here we investigated the conditions for single spike pairing to induce tLTP at older CA3–CA1 synapses. We found that the pairing of single pre- and postsynaptic spikes could induce tLTP in older hippocampus when the postsynaptic neuronal membrane was depolarized and the pairing frequency exceeded ∼4 Hz. The spike frequency requirement is postsynaptic, as tLTP could still be induced with presynaptic stimulation at 1 Hz as long as the postsynaptic spike frequency exceeded ∼4 Hz, suggesting that postsynaptic theta-frequency activity is required for the successful induction of tLTP at older CA3–CA1 synapses. The induction of tLTP was blocked by an NMDA receptor antagonist and by the selective mGluR5 blockers, MPEP and MTEP, whereas activation of mGluR1 and mGluR5 by DHPG relieved the postsynaptic spike frequency requirement for tLTP induction. These results suggest that activation of mGluR5 during single-spike pairing at older CA3–CA1 synapses gates NMDA receptor-dependent tLTP.

Highlights

Synaptic plasticity is believed to be important for hippocampusdependent learning and memory processes (Bliss and Collingridge, 1993; Bliss and Lomo, 1973; Martin et al, 2000; Morris et al, 1986)
Backpropagating action potentials (Stuart and Sakmann, 1994), which act as a coincidence signal during NMDA receptor-mediated Timing-dependent long-term potentiation (tLTP) induction, propagate reliably in dendrites of juvenile CA1 pyramidal neurons (Spruston et al, 1995), but are attenuated by dendritic GABAA receptor-mediated inhibition (Tsubokawa and Ross, 1996), which increases with development in the first few postnatal weeks (Banks et al, 2002)
Consistent with this, we found that pairing single presynaptic stimuli with single postsynaptic spikes at 5 Hz from resting or hyperpolarized membrane potential (À70 mV) failed to induce tLTP in 21e35-day-old rats

Summary

Introduction

Synaptic plasticity is believed to be important for hippocampusdependent learning and memory processes (Bliss and Collingridge, 1993; Bliss and Lomo, 1973; Martin et al, 2000; Morris et al, 1986). Doi:10.1016/j.neuropharm.2012.05.021 with single-spike pairing failed and instead, postsynaptic bursts appeared to be required (Buchanan and Mellor, 2007; Meredith et al, 2003; Pike et al, 1999; Wittenberg and Wang, 2006). This developmental change has been attributed to maturation of GABAA receptor-mediated inhibition (Meredith et al, 2003). In addition to GABAergic maturation, developmental changes in signaling cascades (Yasuda et al, 2003), transmitter release (Bolshakov and Siegelbaum, 1995) and metabotropic glutamate receptor (mGluR) function (Huber et al, 2000) are known to influence the induction of synaptic plasticity, suggesting additional factors that might contribute to the developmental switch in tLTP induction

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