PHASIC BOOSTING OF MEDIAL PERFORANT PATH-EVOKED GRANULE CELL OUTPUT TIME-LOCKED TO SPONTANEOUS DENTATE EEG SPIKES IN AWAKE RATS

Dentate spikes (DSs) are positive-going field potential transients tha t 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 pat h input and are associated with tiring of hilar interneurons and inhib ition of CA3 pyramidal cells. Here we investigated the effect of DSs o n medial perforant path (MPP)-granule cell-evoked transmission in free ly moving rats. The MPP was stimulated selectively in the angular bund le while evoked field potentials and the EEG were recorded with a vert ical multielectrode array in the dentate gyrus. DSs were identified re adily on the basis of their characteristic voltage-versus-depth profil e, amplitude, duration, and state dependency. Using on-line detection of the DS peak, the timing of MPP stimulation relative to single DSs w as controlled. DS-triggered evoked responses were compared with conven tional, manually evoked responses in still-alert wakefulness (awake im mobility) and, in some cases, slow-wave sleep: Input-output curves wer e obtained with stimulation on the positive DS peak (0 delay) and at d elays of 50, 100, and 500 ms. Stimulation on the peak DS was associate d with a significant increase in the population spike amplitude, a red uction in population spike latency, and a decrease in the field excita tory postsynaptic potential (fEPSP) slope, relative to manual stimulat ion. Granule cell excitability was enhanced markedly during DSs, as in dicated 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 inhibit ion of the population spike was unaffected, indicating intact recurren t inhibition during DSs. The results demonstrate enhancement of perfor ant path-evoked granule cell output time-locked to DSs. DSs therefore may function to intermittently boost excitatory transmission in the en torhinal cortex-dentate gyrus-CA3 circuit. Such a mechanism may be imp ortant in the natural induction of long-term potentiation in the denta te gyrus and CA3 regions.