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 ␤ 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 ␤ 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.There is a growing body of evidence from behavioral studies suggesting that the prelimbic (PL) and infralimbic regions of rat frontal cortex are involved in executive functions requiring attentional shift and behavioral flexibility, and in working memory (Kesner 1989;Birrell and Brown 2000; deBruin et al. 2000;Jodo et al. 2000;Mulder et al. 2000). Recent experiments in our laboratory suggest that this region is not only involved in these higher 'executive functions,' but is also important in the posttraining consolidation of memory of a simple odor-reward association. The task used is a three-way discrimination among odors, one of which is associated with a palatable reward. Taking advantage of the spontaneous foraging behavior of the rat, reliable learning is achieved in only three trials massed over a few minutes. The memory endures for at least 1 wk without showing any decline. Immunoreactivity to c-fos antibody has been used as a marker for neuronal activation after training and after a control condition in which rats were exposed to all of the elements of the training but not the odor-reward association. Not surprisingly, many regions were equally activated by both the control and trained conditions. Nevertheless, there were three regions which stood out as differentially activated specifically by the associative training. These were the basolateral amygdala, the ventral orbital cortex, and the PL of the prefrontal cortex (Tronel and Sara 2002). These experiments show that these regions are activated as a result of the training, but they do not prove that they are necessary to the learning or memory process. Subsequent experiments added further support for this notion; injections of the NMDA receptor antagonist APV into the PL immediately after training induced a robust and enduring amnesia expressed when the rats were ...

Elevated Sleep Spindle Density after Learning or after Retrieval in Rats

“…We found a time window during SWS ϳ2 h after the rat learned the odorreward contingency when the noradrenergic neurons of the locus ceruleus, which are usually quiescent during SWS, show a surge of activity that is never seen in animals that have not been in the learning situation (Sara et al, 2005). Learning-related delayed release of noradrenaline in forebrain neurons (Tronel et al, 2004), which are potentially engaged in reactivation during sleep, would serve as an effective signal or "molecular switch" for gene expression during a subsequent REM episode (Ribeiro et al, 1999;Cirelli and Tononi, 2000).…”

The Way an Odor Is Experienced during Aversive Conditioning Determines the Extent of the Network Recruited during Retrieval: A Multisite Electrophysiological Study in Rats

“…to disturb olfactory associative learning (Tronel et al, 2003(Tronel et al, , 2004Boix-Trelis et al, 2007;Carballo-Márquez et al, 2007) and the acquisition and extinction of gustatory aversion (Hernádi et al, 2000;Mickley et al, 2005;Akirav et al, 2006). It is also activated during TPOA retrieval (Dardou et al, 2007).…”

Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats

“…b-ARs include three subtypes, b1, b2, and b3, which are all present in the nervous system. Extensive behavioral and physiological studies have demonstrated that b-AR activation facilitates long-term potentiation (LTP) (Katsuki et al 1997;Lin et al 2003;Straube et al 2003;Gelinas and Nguyen 2005;O'Dell et al 2010;Connor et al 2011) and enhances memory (Ji et al 2003;Tronel et al 2004;Lemon et al 2009;Miranda et al 2011).…”