A cellular analogue of operant conditioning.

Using the hippocampal-slice preparation, we attempted to model operant conditioning in vitro by reinforcing pyramidal cell bursting responses with local micropressure applications of transmitters and drugs. The same injections were administered independently of bursting to provide a "noncontingent" control for direct pharmacological stimulation or facilitation of firing. The results suggested that the bursting responses of individual CA1 pyramidal neurons may be reinforced in a dose-related manner by response-contingent (but not noncontingent) injections of dopamine and the selective dopamine D2 agonist, N-0923. N-0924, a stereoisomer of N-0923 that is largely devoid of D2-agonist activity, failed to reinforce CA1 bursting. Burst-contingent injections of the excitatory neurotransmitter glutamate also failed to reinforce CA1 bursting; indeed, the glutamate applications (whether contingent or random) reduced the likelihood of bursts while increasing the frequency of solitary spikes. Reinforcement delays exceeding 200 ms largely eliminated the reinforcing efficacy of the D2 agonist N-0437 in CA1 operant conditioning. The results are consistent with the suggestion that the behaviorally reinforcing effects of dopaminergic agents can be modeled in vitro in the hippocampal-slice preparation.