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Keywords:

  • inhibition;
  • γ-aminobutyric acid;
  • hippocampus;
  • dendrites

Abstract

Intracellular recordings with K-acetate-filled microelectrodes were performed in slices of the adult rat hippocampus maintained in vitro at 35–36°C to analyse the potentials associated with the orthodromic inhibitory sequence generated by CA1 pyramidal cells. In 43 of 72 cells, stimuli that were delivered in the stratum radiatum induced (i) an initial excitatory postsynaptic potential (EPSP), (ii) an early, hyperpolarizing inhibitory postsynaptic potential (IPSP) (peak latency from the stimulus artefact 20 ms), (iii) an intermediate depolarizing component (peak latency = 60–120 ms; duration = 60-150 ms, and (iv) a late, long-lasting hyperpolarizing IPSP (peak latency = 120–160 ms, duration >400 ms). In the remaining cells the orthodromic inhibitory response lacked the intermediate depolarization. The depolarizing component was selectively blocked by local applications of bicuculline or picrotoxin on the apical dendrites of pyramidal cells. This pharmacological procedure induced an increase in the amplitude of the EPSP that was capable of triggering 2–3 action potentials, but no reduction of the recurrent IPSP which is caused by GABAA receptors located close to the soma. The amplitude and duration of the depolarizing component was enhanced by lowering the temperature in the tissue chamber to 29–31°C or by application of the GABA uptake blocker nipecotic acid, further indicating that the depolarizing component represented an active phenomenon mediated through GABA. Application of the CI- pump blocker furosemide reduced and eventually blocked the early IPSP and the depolarizing component. These data demonstrate that under physiological conditions rat hippocampal pyramidal cells generate a depolarization that is presumably caused by an outwardly directed CI- movement due to the activation of GABAA receptors located on the apical dendrites. This novel mechanism might modulate hippocampal excitability in both physiological and pathophysiological conditions.