Postsynaptic control of hippocampal long-term potentiation.
Long-term potentiation (LTP) in the hippocampus has the property of cooperativity, i.e. greater potentiation is produced if a larger number of afferent fibres is tetanized. The possible involvement of postsynaptic mechanisms in this process was investigated in the CA1 area of the hippocampal slice preparation. Following blockade of postsynaptic inhibition by GABA antagonists, e.g. picrotoxin, the induction of LTP was greatly facilitated. In picrotoxin-treated slices, LTP was induced in a pathway stimulated by single volleys, if these occurred in conjunction with brief tetanic activation of other afferents. This interaction operated over a short period of time (less than 50 ms) and was also present if the inputs were separated in space (cooperativity between inputs to basal and apical dendrites). LTP could be induced by pairing single volley synaptic activation and intracellularly injected depolarizing current pulses, the timing requirements being similar to those observed in the extracellular "conjunction studies". Previous studies have suggested that glutamate receptor channels of the N-methyl-D-aspartate (NMDA) type are somehow involved in LTP induction. Evidence presented here shows that activation leading to LTP evokes a potential which is sensitive to the NMDA receptor blocker 2-amino-5-phosphonovalerate (APV), indicating passage of current through NMDA receptor channels. The results suggest that hippocampal LTP depends on simultaneous presynaptic transmitter release and postsynaptic depolarization in a manner analogous to the model proposed by HEBB (1949) for associative learning. Furthermore, it is proposed that the required pre- and postsynaptic interaction is handled by the NMDA receptor channel complex, which is known to have the required voltage and transmitter sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D018756:GABA Antagonists; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D016202:N-Methylaspartate; D010852:Picrotoxin / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D015763:2-Amino-5-phosphonovalerate; D000927:Anticonvulsants; D001224:Aspartic Acid; D018756:GABA Antagonists; D016202:N-Methylaspartate; D010852:Picrotoxin; D014633:Valine