USE-DEPENDENT CHANGES IN SYNAPTIC EFFICACY IN RAT PREFRONTAL NEURONS INVITRO

1. An in vitro slice preparation of rat prefrontal cortex was used to analyse the responses of layer V pyramidal cells to electrical stimulation of layer II. We also studied the long‐lasting modifications of synaptic efficacy following high‐frequency stimulation of the same region. 2. Stable intracellular recordings were obtained from forty‐three regular spiking pyramidal cells. The input resistance was 56 +/‐ 18 M omega (mean +/‐ S.D.) at a resting membrane potential of ‐71 +/‐ 4 mV. 3. At rest, a single stimulus of increasing strength evoked a monophasic, purely depolarizing postsynaptic potential (PSP) of increasing amplitude. In neurons recorded with potassium acetate‐filled micropipettes, membrane depolarization disclosed an excitatory‐inhibitory (EPSP‐IPSP) sequence (onset latency of the EPSP, 3.6 +/‐ 0.6 ms). 4. Superfusion with the non‐N‐methyl‐D‐aspartate (NMDA) receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) reduced the EPSP and suppressed the IPSP. The small EPSP which remained was blocked by the NMDA receptor antagonist, D,L‐2‐amino‐5‐phosphonovalerate (APV). 5. In five cells, administration of 0.5 mumol l‐1 bicuculline revealed a postsynaptic NMDA component in the evoked response as evidenced by its anomalous voltage dependence in the presence of Mg2+ and its sensitivity to APV. In these cells the latency of the APV‐sensitive EPSP was the same as that of the APV‐insensitive EPSP. 6. In six cells superfused with a high‐Mg2+, low‐Ca2+ artificial cerebrospinal fluid (ACSF) a small monosynaptic EPSP remained which had the same latency as the PSP recorded in control ACSF. 7. Patterned high‐frequency stimulation (50‐100 Hz) was applied to the afferents of twenty‐eight neurons (twenty‐three of them were recorded in the presence of bicuculline). During the train the membrane potential depolarized some 20 mV and each stimulus evoked a small PSP. The tetanic stimulation was followed by a short‐term enhancement of the PSP amplitude and a slight increase in membrane input resistance. 8. Out of the twenty‐eight cells, twenty‐four showed long‐lasting (over 30 min) modifications of the PSP. Long‐term depression (LTD) of the evoked PSP was observed in fourteen cells and long‐term potentiation (LTP) in ten cells. There was no significant change in the steady‐state membrane properties and in the latency of the response. 9. In 64% of the cells that showed LTD and 70% of those that showed LTP of synaptic efficacy, the latency of the enhanced or depressed component of the PSP was the same as the control.(ABSTRACT TRUNCATED AT 400 WORDS) © 1990 The Physiological Society