Developmental and regional differences in the consolidation of long-term potentiation.
The alpha5beta1 integrin is present in high concentrations in the apical dendrites of pyramidal neurons in adult rats but is virtually absent in the basal dendrites. Moreover, alpha5beta1 does not appear in apical dendritic branches until the third post-natal week. Given that integrins contribute to the consolidation of synaptic plasticity, these results raise the possibility of developmental and regional differences in the stability of long-term potentiation (LTP). The present study tested this point using a LTP reversal paradigm in field CA1 of hippocampal slices. In accord with earlier reports, low-frequency afferent stimulation (5 Hz) introduced 30 s after theta burst stimulation (TBS) completely reversed LTP but was ineffective 30 min and 60 min later in slices from adult rats. The same low-frequency trains caused a partial reversal of LTP when applied 30 and 60 min post-TBS in slices from 21-day-old rats and a complete reversal at all time points in slices from 10-day-old rats. LTP in the basal dendrites of adult rats did not fully consolidate; i.e. potentiation was partially reversed by low-frequency stimulation even after delays of 30 or 60 min. Moreover, spaced (10 min) applications of 5- Hz pulses beginning at 30 min post-TBS completely erased LTP. The reversal effect in both apical and basal dendrites was blocked by N-methyl-D-aspartic acid receptor antagonists but an integrin antagonist had differential effects across the two dendritic domains. These results constitute evidence that the stability of LTP increases with age in the apical dendrites but remains incomplete even in adulthood in the basal dendrites. The possibilities that the developmental and regional variations in LTP consolidation are correlated with integrin expression and linked to different types of memory processing are discussed.
Kramár
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EA
Department of Psychiatry and Human Behavior, 101 Theory Drive, #250 Research Park, University of California, Irvine, CA 92612-1695, USA. ekramar@uci.edu
Lynch
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D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D066298:In Vitro Techniques; D039001:Integrin alpha Chains / Q000037:antagonists & inhibitors / Q000145:classification / Q000276:immunology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009434:Neural Pathways; D009842:Oligopeptides / Q000494:pharmacology; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D039001:Integrin alpha Chains; D009842:Oligopeptides; D016194:Receptors, N-Methyl-D-Aspartate; C056639:2-amino-5-phosphopentanoic acid; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline; D014633:Valine