Slow Presynaptic and Fast Postsynaptic Components of Compound Long-Term Potentiation

Abstract

Long-term potentiation (LTP) mediates learning and memory in the mammalian hippocampus. Whether a presynaptic or postsynaptic neuron principally enhances synaptic transmission during LTP remains controversial. Acute hippocampal slices were made from transgenic mouse strains that express synaptopHluorin in neurons. SynaptopHluorin is an indicator of synaptic vesicle recycling; thus, we monitored functional changes in presynaptic boutons of CA3 pyramidal cells by measuring changes in synaptopHluorin fluorescence. Simultaneously, we recorded field excitatory postsynaptic potentials to monitor changes in the strength of excitatory synapses between CA3 and CA1 pyramidal neurons. We found that LTP consists of two components, a slow presynaptic component and a fast postsynaptic component. The presynaptic mechanisms contribute mostly to the late phase of compound LTP, whereas the postsynaptic mechanisms are crucial during the early phase of LTP. We also found that protein kinase A (PKA) and L-type voltage-gated calcium channels are crucial for the expression of the presynaptic component of compound LTP, and NMDA channels are essential for that of the postsynaptic component of LTP. These data are the first direct evidence that presynaptic and postsynaptic components of LTP are temporally and mechanistically distinct.

Relationship between increase in astrocytic GLT-1 glutamate transport and late-LTP

“…Indeed, a slowly developing increase in glutamate release during L-LTP has been visualized using fluorescent dyes or mice expressing SynaptopHluorin in presynaptic boutons (Zakharenko et al 2001;Bayazitov et al 2007). The simplest explanation for elimination of expression of late LTP by DHK is that glutamate accumulated and subsequently inhibited expression of LTP by increased desensitization of AMPA receptors and/or excessive activation of metabotropic and NMDA receptors.…”

“…An increase in release of glutamate by presynaptic terminals has been observed during L-LTP (Zakharenko et al 2001;Bayazitov et al 2007). Thus, inhibition of expression of L-LTP by DHK could be the result of an accumulation of extracellular glutamate, which leads to activation of metabotropic glutamate receptors during the late phase of LTP.…”

The Muscarinic Long-Term Enhancement of NMDA and AMPA Receptor-Mediated Transmission at Schaffer Collateral Synapses Develop through Different Intracellular Mechanisms

“…Although considerable effort has been made to elucidate the causal and expression mechanisms of long-term potentiation (LTP), they remain controversial and more varied than previously considered (Johnston et al, 1992;Cohen et al, 1998;Chevaleyre et al, 2006;Bayazitov et al, 2007;Campanac and Debanne, 2007;Fernández de Sevilla et al, 2008;Fidzinski et al, 2008). The classical "Hebbian" LTP (LTP H ) (Hebb, 1949) requires activation of NMDA receptors (NMDARs) and is caused by an enhancement of AMPA receptor (AMPAR)-mediated transmission (Malinow and Malenka, 2002;Bredt and Nicoll, 2003;Collingridge et al, 2004;Malenka and Bear, 2004).…”

Photochemical Inactivation Analysis of Temporal Dynamics of Postsynaptic Native AMPA Receptors in Hippocampal Slices

“…Many studies have suggested that the expression mechanism of LTP may shift with time and that gradual increases in postsynaptic AMPAR occur over time scales of hours (Bayazitov et al, 2007). Lack of gradual synaptic delivery up to 3 h was not due to insufficient synaptic activation by the stimulation protocols used in this study (Huang and Kandel, 1994;Nguyen and Kandel, 1997).…”

“…Several studies suggested that the underlying mechanism of LTP shifts with time over several hours (Nayak et al, 1998;Bayazitov et al, 2007;Tanaka et al, 2008). It was also pointed out that subunit composition is transiently changed within 30 min after LTP induction (Plant at al., 2006;Adesnik and Nicoll, 2007).…”