JOURNALOF NEUROPHYSIOLOGY Vol. 60, No. 3, September 1988. Printed in U.S.A. Postsynaptic Control of the Induction of Long-Term Changes in Efficacy of Transmission at Neocortical Synapses in Slices of Rat Brain LYNN J. BINDMAN, IS. P. S. J. MURPHY, AND S. POCKETT Department of Physiology, University CoZZege London, London WC1 E 6BT, UnitedKingdom SUMMARY AND CONCLUSIONS 1. Long-term potentiation (LTP) is an en- during, activity-induced increase in the efficacy of synaptic transmission, which has been considered as a possible neural substrate for learning. Recent experiments have shown that LTP can be induced in hippocampal CA1 neurons when a presynaptic volley is paired repetitively with depolarization of the postsynaptic cell, brought about with intra- cellularly applied depolarizing current pulses (20,33). We have repeated these experiments in neocortical neurons, in transverse slices of rat sensorimotor cortex in vitro. 2. Stable intracellular recordings were ob- tained from 28 neurons (mean resting poten- tial -78 mV, mean spike amplitude 95 mV, mean input resistance 4 1 MQ) mostly in lay- ers V and VI. Two different afferent pathways were stimulated alternately at 0.2 Hz to evoke subthreshold composite excitatory postsyn- aptic potentials (EPSPs). One micromolar bi- cuculline methiodide was added to the bath- ing medium in most experiments. 3. Repetitive pairing of one afferent volley with a coincident intracellular depolarizing current pulse (100-200 ms long) of a magni- tude sufficient to make the neuron fire 6 to 13 action potentials/pulse, gave rise after 30-50 pairings in 4 neurons to a significant endur- ing increase in the amplitude of the paired EPSP. The increase persisted without decre- ment for as long as the recording continued (range 15-50 min after the pairing ended) but the amplitude of the unpaired EPSP was un- changed. ‘During the LTP, the membrane po- tential and the apparent input resistance of the postsynaptic neurons were also un- changed. 4. In two cells a significant prolonged de- pression of the paired EPSP was induced while the unpaired EPSP was unaffected. Membrane potential and input resistance were not changed. In the remaining 22 cells neither the paired nor the unpaired EPSP was altered. 5. Brief, tetanic stimulation was applied to one afferent pathway in 11 of the neurons in which postsynaptic stimulation had been in- effective. A variety of effects was produced (LTP, depression, or posttetanic potentia- tion). All the effects of tetanic stimulation were confined to the stimulated pathway. 6. We conclude that LTP can be produced in some neocortical neurons by pairing a pre- synaptic volley with postsynaptic depolariza- tion, in an experimental paradigm that con- forms to Hebb’s (17) model of associative conditioning. Depression of the paired EPSP was produced in other cells with the same ex- perimental design. LTP was conjunctively produced in - 15% of paired EPSPs in our neocortical recordings compared with a re- ported frequency of 80% in hippocampal CA1 pyramidal neurons, which may reflect a greater functional heterogeneity of sensori- motor neocortical cells. INTRODUCTION Models of the mechanisms of associative learning such as that of Hebb (17) postulate that a synapse is strengthened only when pre- synaptic volleys occur in conjunction with firing of the postsynaptic cell. The production of LTP in the neocortex and hippocampus has been shown to conform to this require- ment (5, 15, 20). In one experimental para- digm, LTP of single test volleys to hippocam- 0022-3077/88 $1.50 Copyright 0 1988 The American Physiological Society 1053 wnloaded from www.physiology.org/journal/jn by ${individualUser.givenNames} ${individualUser.surname} (133.006.082.173) on January 14, 20