Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice

Abstract

Long-term potentiation (LTP) is an enhancement of synaptic strength that can be produced by pairing of presynaptic activity with postsynaptic depolarization. LTP in the hippocampus has been extensively studied as a cellular model of learning and memory, but the nature of the underlying synaptic modification remains elusive, partly because our knowledge of central synapses is still limited. One proposal is that the modification is postsynaptic, and that synapses expressing only NMDA (N-methyl-D-aspartate) receptors before potentiation are induced by LTP to express functional AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors. Here we report that a high proportion of synapses in hippocampal area CA1 transmit with NMDA receptors but not AMPA receptors, making these synapses effectively non-functional at normal resting potentials. These silent synapses acquire AMPA-type responses following LTP induction. Our findings challenge the view that LTP in CA1 involves a presynaptic modification, and suggest instead a simple postsynaptic mechanism for both induction and expression of LTP.

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

“…Our observations are consistent with those reported recently for amphetamine and several other drugs of abuse (Ungless et al, 2001;Saal et al, 2003). In the hippocampus, an increase in the AMPAR component of the excitatory postsynaptic response occurs at synapses that have undergone LTP (Kauer et al, 1988;Isaac et al, 1995;Liao et al, 1995;Malinow and Malenka, 2002). By extension, the increased AMPAR/NMDAR ratios in the VTA suggest that excitatory VTA synapses in animals exposed to drugs of abuse are potentiated 24 h later.…”

Transient Plasticity of Hippocampal CA1 Neuron Glutamate Receptors Contributes to Benzodiazepine Withdrawal-Anxiety

“…Activity-dependent recruitment of AMPARs is well described (Liao et al, 2001;O'Brien et al, 1998;Turrigiano, 2000) and is a final common pathway mediating activity-dependent changes in synaptic efficacy at CA1 excitatory synapses both in vivo and in vitro (Baudry and Lynch, 2001;Liao et al, 1995;Lledo et al, 1998;Nayak et al, 1998;Zamanillo et al, 1999). Activitydependent changes in synaptic function are primarily the consequence of intracellular Ca 2 þ -dependent biochemical cascades and involve changes in synaptic AMPAR number and/or function (Hayashi et al, 2000;Song and Huganir, 2002).…”

Decreased Frequency But Not Amplitude of Quantal Synaptic Responses Associated with Expression of Corticostriatal Long-Term Depression

“…Such a change could occur by a complete loss of postsynaptic responsiveness at high-Pr synapses. Although LTD at central synapses has not been shown to involve an increase in the number of silent synapses, some evidence suggests that the induction of CA1 LTP involves a decrease in the number of silent synapses that may be produced by the upregulation of the number or activity of AMPA receptors (Isaac et al, 1995;Liao et al, 1995). The mechanism underlying changes in the number of silent synapses appears to be viable even for preexisting f unctional synapses, leading to an increase in quantal amplitude after LTP induction (Liao et al, 1995).…”

“…Although LTD at central synapses has not been shown to involve an increase in the number of silent synapses, some evidence suggests that the induction of CA1 LTP involves a decrease in the number of silent synapses that may be produced by the upregulation of the number or activity of AMPA receptors (Isaac et al, 1995;Liao et al, 1995). The mechanism underlying changes in the number of silent synapses appears to be viable even for preexisting f unctional synapses, leading to an increase in quantal amplitude after LTP induction (Liao et al, 1995). Consistent with these findings, changes in quantal amplitude as well as frequency associated with LTP and LTD have been detected using analysis of Sr 2ϩ -induced asynchronous quantal release in the CA1 region of hippocampus (Oliet et al, 1996(Oliet et al, , 1997.…”