No abstract

Synaptic responses in hippocampal granule cells to stimulation of their afferent fibers from the entorhinal cortex fluctuate with a 24-hour period. The phase of this cycle for rats and monkeys depends on whether the animal is naturally nocturnal or diurnal. In a rat blinded by enucleation, the rhythm persists but drifts out of phase with the rhythm of sighted controls.

SUMMARY1. The relationship between long-term potentiation (l.t.p.) and the release of endogenous amino acid transmitters has been investigated in the dentate gyrus of rats anaesthetized with urethane.2. The molecular layer was perfused with artificial cerebrospinal fluid using a push-pull cannula. The perfusate was collected and analysed for glutamate, aspartate, glycine, glutamine and y-aminobutyric acid (GABA) using high-performance liquid chromatography (h.p.l.c.) with fluorometric detection.3. Recording electrodes were attached to the cannula to enable responses evoked by test stimuli to the perforant path to be monitored in the molecular and cell body layers.4. Perfusion was continued for 3 h while test stimuli were delivered to the perforant path at 30 s intervals. In the control group (n = 8), no further stimulation was given. In a second group (n = 8), a single high-frequency train (250 Hz for 200 ms) was delivered at the end of the first hour to induce l.t.p. The average potentiation of the slope of the excitatory post-synaptic potential (e.p.s.p.) 2 h later was 150. In a third group (n = 8), the train to the perforant path was paired with a train to the commissural input to the dentate gyrus, a procedure which blocks the induction of l.t.p.5. In the potentiated group, there was an increase in the concentrations of glutamate and aspartate following the induction of l.t.p., relative to the decline seen in corresponding periods of the control group. This increase remained statistically significant for 1-5 h in the case of glutamate and for 45 min in the case of aspartate.6. There were no l.t.p.-associated changes in the release of glutamine or glycine; there was an indication that l.t.p. may be associated with a decrease in the release of GABA.7. Increasing the frequency and intensity of perforant path activation resulted in enhanced concentrations of glutamate and aspartate in the perfusate; no such changes occurred when granule cells were activated antidromically.8. We discuss the origin of the relative increases in the concentration of glutamate and aspartate which are found in the perfusate following the induction of l.t.p. and

Stimulation of the contralateral hippocampus in the hilar region had a marked effect on granule cell excitability in the fascia dentata. The primary effect was to block the population spike that otherwise occurred in response to perforant path stimulation. In contrast, the size the excitatory post-synaptic potential component of the perforant path-evoked field potential was only slightly reduced. The population spike diminution began at short latency (3.5 msec), beginning at about 1.0 msec after the onset of the slow component of the potential evoked by the contralateral stimulus. The completeness and duration of this population spike diminution depended on the contralateral stimulus intensity. The maximum duration was less than 40 msec in unanesthetized rats and more than 100 msec in rats under pentobarbital anaesthesia. Bicuculline did not diminish the field potential evoked by the contralateral stimulus but it did prevent the stimulus from blocking the perforant path population spike and, instead, permitted a weak facilitation of the population spike. The normal reduction of the population spike was not mediated by recurrent inhibition, secondary to granule cell activation, since it occurred whether or not the granule cells were inhibited at the time of contralateral stimulation. These results imply that the initial main effect on fascia dentata granule cells of activity in the contralateral hilus is a gamma-aminobutyric-acid-mediated inhibition. This effect most probably involves commissural excitation of local inhibitory interneurons. The direct excitatory action of commissural fibers on granule cells, by comparison, is very weak.