Potentiation or depression of synaptic efficacy in the dentate gyrus is determined by the relationship between the conditioned and unconditioned stimulus in a classical conditioning paradigm in rats.

Learning a conditioned stimulus (CS)-unconditioned stimulus (US) association is accompanied by a variety of long-lasting changes in physiology and chemistry of the synapse in the dentate gyrus. To determine the time course of synaptic modification during learning, changes in the perforant path-dentate gyrus-evoked field potentials were measured in rats performing a classical conditioning (paired tone and footshock) or pseudoconditioning (unpaired tone and footshock) task. Over the course of 4 days of training, differential changes in the evoked response were observed in the two groups. In the conditioned group, there was an increase in the slope of the excitatory postsynaptic potential (EPSP) which started after five tone-shock paired trials and lasted for more than 40 min, outlasting the training session by 20 min. In contrast, a decrease in the slope of the EPSP which commenced after training and lasted for at least 1 h was observed in the pseudoconditioned group. In both groups there was a prolonged decrease in the amplitude of the population spike. The increase in the EPSP was reduced and the duration tended to shorten over days of training in the conditioned group, whereas in the pseudoconditioned group the decrease in the EPSP tended to increase. Off-line analysis of suppression of lever-pressing for food reward during the presentation of the tone, indicated that the conditioned rats had learned the tone-footshock association. Temperature was measured in the dentate gyrus of rats undergoing an identical procedure. In both groups slight temperature increases were observed, with no difference in amplitude and time-course between the groups. The differential effect of conditioning and pseudoconditioning on the evoked response and changes in temperature eliminate the possibility that effects of stress, arousal and muscular effort are the primary cause of the changes in the EPSP. The results suggest that behavioural events can exert bidirectional control of synaptic strength of entorhinal cortex inputs to the dentate gyrus and that the sign of synaptic modification is at least in part determined by the temporal relationship between these events. The data are discussed in terms of the type of neural activity that may mediate the processing of information in the dentate gyrus.