Delayed Onset of Potentiation in Neocortical EPSPs during Long-Term Potentiation (LTP) — A Postsynaptic Mechanism or Heterogeneous Synaptic Inputs ?
Long-term potentiation (LTP) is an activity-dependent, long-lasting change in the efficacy of synaptic transmission, which is a possible neural substrate for learning and memory. We have induced LTP at some synapses in slices of rat sensorimotor cortex in vitro, by using either brief tetanic stimulation of afferent axons or an associative, postsynaptic method of induction. We were successful in inducing LTP of excitatory postsynaptic potentials (EPSPs) in 11 out of 53 neurones in layers III, V or VI.
In view of the importance of N-methyl-D-aspartate (NMDA) receptor activation for the induction of LTP in neocortex, as in regions of hippocampus, we hypothesized that the failures of induction of LTP might be due to a lack of NMDA-receptor mediated activity in the afferent pathway onto layer V and VI neurones. Hence we bath-applied the selective NMDA-receptor antagonist 2-amino-5- phosphonopentanoic acid (AP5) and examined its effect on composite PSPs evoked in layer V and VI neurones. We found that 94% of PSPs (44/47) were partly mediated by NMDAreceptor activity, so a lack of functioning NMDA receptors was not likely to be the reason for failures of induction of LTP by afferent tetanic stimulation.
When we induced LTP (in the absence of AP5) and applied AP5 15 to 20 min after the establishment of LTP, the expression of LTP was reversibly reduced: during LTP, synaptic responses consisted of an early AP5-insensitive component and a later AP5-sensitive component. This was seen in both EPSPs and field potentials in layers V and VI.
Although the depolarising slope of most of the neocortical EPSPs was increased during the expression of LTP, we found that in 9/11 short latency EPSPs the onset of the potentiated component of the EPSP was delayed by a few ms with respect to the onset of the EPSP. In 7 of the 9 EPSPs the LTP was induced postsynaptically by pairing an evoked EPSP repetitively with intracellular depolarising pulses. The explanation for the delayed onset of the potentiated component in these EPSPs could be either that a postsynaptic voltage-sensitive mechanism was involved, or that the afferent terminals on the neurones were heterogeneous. The afferents responsible for the shortest latency components of the neocortical EPSPs may not be capable of sustaining LTP.
KeywordsSensorimotor Cortex Layer Versus Test Shock Function NMDA Receptor Bicuculline Methiodide
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