Hormonal and monoamine signaling during reinforcement of hippocampal long-term potentiation and memory retrieval

Abstract

Recently it was shown that holeboard training can reinforce, i.e., transform early-LTP into late-LTP in the dentate gyrus during the initial formation of a long-term spatial reference memory in rats. The consolidation of LTP as well as of the reference memory was dependent on protein synthesis. We have now investigated the transmitter systems involved in this reinforcement and found that LTP-consolidation and memory retrieval were dependent on ␤-adrenergic, dopaminergic, and mineralocorticoid receptor (MR) activation, whereas glucocorticoid receptors (GRs) were not involved. Blockade of the ␤-adrenergic signaling pathway significantly increased the number of reference memory errors compared with MR and dopamine receptor inhibition. In addition, ␤-adrenergic blockade impaired the working memory. Therefore, we suggest that ␤-adrenergic receptor activation is the main signaling system required for the retrieval of spatial memory. In addition, other modulatory interactions such as dopaminergic as well as MR systems are involved. This result points to specific roles of different modulatory systems during the retrieval of specific components of spatial memory. The data provide evidence for similar integrative interactions between different signaling systems during cellular memory processes.

Hippocampal receptor complexes paralleling LTP reinforcement in the spatial memory holeboard test in the rat

“…An in vivo study has shown that the D1R is crucial for maintenance of LTP in CA1 but does not modulate LTP in the dentate gyrus [83] when measured over 4 hours without a specific behavioural context. However, modulatory inputs affecting the dopaminergic system and enhancing LTP in the dentate gyrus have been reported in a context of reward [54,1,42] and reward associated spatial memories [53,37]. These and the present study suggest that previous activity and incoming information during LTP-induction significantly determines different mechanisms involved in LTP-maintenance.…”

“…Whereas the trained group showed persistent potentiation at all post-tetanic time points this potentiation in the untrained group declined towards baseline within four hour. Thus, as a consequence of training the early-phase of LTP was reinforced into the protein-synthesis dependent late form as has been described in earlier studies [87] [53]. The key experiments to understand the molecular basis of the behaviourally induced LTP-reinforcement are the characterization of the involved complexes of glutamate and monoaminergic receptors.…”

Effects of midazolam on acquisition and extinction of conditioned taste aversion memory in rats

“…In the previous paper [15], we reported that subhypnotic but not hypnotic doses of propofol, one of non-benzodiazepine anesthetic agents, which has GABA-potentiating properties [12,23,25] In the present study, we examined the effect of anesthetics applied between CS and US presentations on the long-term CTAM using several dosages of benzodiazepine agent, midazolam and compared the effects of midazolam with those of non-benzodiazepine, propofol. Furthermore, noradrenergic system has been reported to play an important role in the memory retention [7,18,19]. Therefore, we examined the effect of yohimbin , an α2 adrenoceptor antagonist on acquisition and retention of CTAM.…”

“…Midazolam also represented optimal concentration in acceleration effect on extinction of CTAM (Fig.2). However, tendency for midazolam to suppress the AI was observed, and post CS-injection of 613 µM midazolam significantly suppressed the AI.Midazolam generated the optimal suppression of RI at higher concentration (75 µM) than propofol (14 µM) [15], while midazolam represented steeper dose-response relationship than propofol.Recently, noradrenergic system has been reported to play an important role in the memory retention [7,18,19]. Therefore, we attempted to apply 1 mg/kg yohimbin, anα2 adrenoceptor antagonist, instead of anesthetics.…”

“…Recently, noradrenergic system has been reported to play an important role in the memory retention [7,18,19]. Therefore, we attempted to apply 1 mg/kg yohimbin, anα2 adrenoceptor antagonist, instead of anesthetics.…”