Continuous blockade of GABA-ergic inhibition induces novel forms of long-lasting plastic changes in apical dendrites of the hippocampal cornu ammonis 1 (CA1) in vitro.
Hippocampal long-term potentiation (LTP) is considered as a fundamental mechanism for learning and memory formation. A role for GABA was reported for the induction and early but not late maintenance of LTP. We have now investigated whether GABA-receptor function is involved in the prolonged maintenance of LTP (>4 h) at afferent synapses at apical dendrites of cornu ammonis 1 (CA1)-pyramidal neurons in hippocampal slices in vitro. Our data demonstrate that GABA-receptor mediated events are not required for conventional, tetanically-induced early- or late-LTP in the hippocampal CA1-region in vitro. Inhibition of GABA-ergic transmission did not negatively influence either early- or late-LTP. In contrast, an additional facilitation was observed at time points corresponding to the establishment of late-LTP (after 3-4 h). Investigation of a second, non-tetanized control input to the same neuronal population revealed that the elevated potentiation of late-LTP in the tetanized input was not LTP-specific. Therefore, we have examined, whether continuous application of GABA-receptor inhibitors also affected the time course of the recorded potentials when a low-frequency stimulation protocol was used. Under these conditions two distinct forms of a late-onset potentiation occurred 5-6 h after drug application. Investigation of mechanisms responsible for this prolonged enhancement of potentials revealed that the higher form of potentiation (potentiation levels above 200%) was dependent on presynaptic activity and N-methyl-d-aspartate (NMDA)-receptor activation, whereas the lower form (potentiation less than 200%) did not require these mechanisms. However, the latter potentiation was prevented by nifedipine, an L-type voltage-dependent calcium channel inhibitor.
Frey
J U
JU
Leibniz Institute for Neurobiology, Department of Neurophysiology, Magdeburg, Germany. frey@ifn-magdeburg.de
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D017774:Long-Term Potentiation; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission
D020746:Calcium Channels, L-Type; D018756:GABA Antagonists; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate