Noradrenergic action in prefrontal cortex in the late stage of memory consolidation

Abstract

These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively motivated foraging task based on olfactory discrimination. They were injected with a beta adrenergic receptor antagonist into the PL 5 min or 2 h after training and tested 48 h later. Rats injected at 2 h showed amnesia, whereas those injected at 5 min had good retention, equivalent to saline-injected controls. Monitoring extracellular noradrenaline efflux in PL by in vivo microdialysis during the first hours after training revealed a significant increase shortly after training, with a rapid return to baseline, and then another increase around the 2-h posttraining time window. Pseudo-trained rats showed a smaller early efflux and did not show the second wave of efflux at 2 h. These results confirm earlier pharmacological and immunohistochemical studies suggesting a delayed role of noradrenaline in a late phase of long-term memory consolidation and the engagement of the PL during these consolidation processes.

Figure 1

Timolol injections in the prelimbic cortex. Latency to make the correct response over the last training trial and the retention trials. Groups were treated 5 min or 2 h after training with timolol or saline. The retention was 48 h later. The Tim-2 h group is significantly different from the sal-2 h (*P < 0.01) and from the Tim-5 min group ( P < 0.01) at the retention test. The performances at the first test trial for the Tim-2 h group were significantly different from both the last acquisition trial (♦P < 0.01) and the second test trial (*P < 0.01), showing an amnesic effect and the ability to relearn the task, respectively.

Figure 2

Timolol injections in the prelimbic cortex. Number of errors before making the correct response over the last training trial and the retention trials. Groups were treated 5 min or 2 h after training with timolol or saline solution. The retention was 48 h later. The Tim-2 h group is significantly different from the sal-2 h (*P < 0.01) and from the Tim-5 min group ( P < 0.01) at the retention test. The performances at the first test trial for the Tim-2 h group were significantly different from both the last acquisition trial (♦P < 0.01) and the second test trial (*P < 0.01), showing an amnesic effect and the ability to relearn the task, respectively.

Figure 3

Latency to make the nose-poke response to the target odor during the three acquisition trials and the three retention trials, 6 d later. There was a significant decrease in the time to make the correct response (*) over the three acquisition trials and no difference between the last acquisition trial and the first retention trial.

Figure 4

Extracellular NE in the prelimbic cortex in trained and pseudotrained groups (mean percentage of basal level). *: significant difference between the trained and the pseudotrained group and between the 112-min and 128-min time points in the trained group (P < 0.01). Note the difference after training, the return to baseline for both groups, and the significant increase in efflux in trained rats at 128 min after training.