TRANSIENT CHANGES IN EXCITABILITY OF RABBIT CA3 NEURONS WITH A TIME-COURSE APPROPRIATE TO SUPPORT MEMORY CONSOLIDATION

1. The excitability of CA3 pyramidal neurons was assessed with intrace llular recordings in hippocampal slices from behaviorally naive rabbit s. CA3 pyramidal neurons had large (-13.1 +/- 0.3 mV; mean +/- SE) pos tburst afterhyperpolarizations (AHPs) and exhibited robust spike-frequ ency adaptation (accommodation) to prolonged (800-ms) depolarizing cur rent injection at resting potentials of -68 mV. AHP and accommodation measures differed in scale but not in kind from those obtained in stab le recordings from CA1 pyramidal neurons in the same slices or from th e same rabbits, with CA3 neurons having larger longer AHPs but fewer s pikes during accommodation. 2. Groups of rabbits were trained in a sim ple, associative-learning task, trace eye-blink conditioning, which re quires an intact hippocampus for successful acquisition. Memory consol idation in this task also involves the hippocampus, whereas long-term retention of the learned response does not. The time course and magnit ude of learning-specific changes in excitability were assessed in 201 CA3 pyramidal neurons. 3. Learning increased the excitability of CA3 p yramidal neurons soon after acquisition (within 1-24 h). The mean post burst AHP was reduced to approximately half (-6.4 +/- 0.3 mV) the basa l amplitude of the AHP observed in naive controls. The area and durati on of the postburst AHP similarly were reduced. Approximately half of all pyramidal neurons tested soon after learning exhibited significant ly reduced AHPs, whereas none exhibited enhanced AHPs. 4. Trace condit ioning also reduced accommodation of CA3 pyramidal neurons 1-24 h afte r learning. Neurons from successfully trained rabbits fired significan tly more action potentials (5.6 +/- 1.5) in response to prolonged depo larization than did neurons from naive controls (4.1 +/- 0.2). The mag nitude of the learning-specific change in accommodation was less than that for the AHP. Approximately 45% of neurons tested exhibited signif icantly reduced accommodation soon after learning. 5. Both learning-sp ecific changes in CA3 increased neuronal excitability. Both changes we re highly time dependent. AHPs were reduced maximally 1-24 h after lea rning, then increased, returning to basal (naive) levels within 7 days and remaining basal thereafter. The decay rate of accommodation to ba sal levels preceded that of the AHP by several days. 6. Other membrane properties, including action potential characteristics, resting poten tial, and input resistance, were unchanged by learning. The restrictio n of the observed changes to two interrelated measures of excitability concurs with earlier reports that learning-specific changes in the ma mmalian hippocampus are linked to changes in a limited number of membr ane conductances. 7. Learning, not long-term memory or performance of the learned behavior, was linked to the excitability changes. Neurons from rabbits that failed to acquire the task after considerable traini ng exhibited no excitability changes. Neurons from pseudo-conditioned rabbits were indistinguishable from neurons of behaviorally naive cont rols. Finally, neurons from rabbits that explicitly demonstrated long- term retention of the conditioned response were indistinguishable from those of naive controls. 8. Behavioral changes persisted for extremel y long periods, but the observed changes in hippocampal excitability w ere transient and greatest soon after learning. Excitability was enhan ced for a period of a few days, a period demonstrated in other eyeblin k studies to be required for memory consolidation. Because hippocampal excitability then returned to basal levels but memory of the learned task persisted, postconsolidation memory traces (the ''engram'') must be extrahippocampal.