Phasic boosting of medial perforant path-evoked granule cell output time-locked to spontaneous dentate EEG spikes in awake rats

Abstract

Dentate spikes (DSs) are positive-going field potential transients that occur intermittently in the hilar region of the dentate gyrus during alert wakefulness and slow-wave sleep. The function of dentate spikes is unknown; they have been suggested to be triggered by perforant path input and are associated with firing of hilar interneurons and inhibition of CA3 pyramidal cells. Here we investigated the effect of DSs on medial perforant path (MPP)-granule cell-evoked transmission in freely moving rats. The MPP was stimulated selectively in the angular bundle while evoked field potentials and the EEG were recorded with a vertical multielectrode array in the dentate gyrus. DSs were identified readily on the basis of their characteristic voltage-versus-depth profile, amplitude, duration, and state dependency. Using on-line detection of the DS peak, the timing of MPP stimulation relative to single DSs was controlled. DS-triggered evoked responses were compared with conventional, manually evoked responses in still-alert wakefulness (awake immobility) and, in some cases, slow-wave sleep. Input-output curves were obtained with stimulation on the positive DS peak (0 delay) and at delays of 50, 100, and 500 ms. Stimulation on the peak DS was associated with a significant increase in the population spike amplitude, a reduction in population spike latency, and a decrease in the field excitatory postsynaptic potential (fEPSP) slope, relative to manual stimulation. Granule cell excitability was enhanced markedly during DSs, as indicated by a mean 93% increase in the population spike amplitude and a leftward shift in the fEPSP-spike relation. Maximum effects occurred at the DS peak, and lasted between 50 and 100 ms. Paired-pulse inhibition of the population spike was unaffected, indicating intact recurrent inhibition during DSs. The results demonstrate enhancement of perforant path-evoked granule cell output time-locked to DSs. DSs therefore may function to intermittently boost excitatory transmission in the entorhinal cortex-dentate gyrus-CA3 circuit. Such a mechanism may be important in the natural induction of long-term potentiation in the dentate gyrus and CA3 regions.