The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

Abstract

The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear training to acoustic conditioned stimulus (CS) and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as the conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way, there was no interference with normal NBM function during either acquisition or retrieval phases, allowing any amnesic effect to be due only to consolidation disruption. The results show that for contextual fear response memory consolidation, NBM functional integrity is necessary up to 24 h post-acquisition. On the other hand, NBM functional integrity was shown to be necessary for memory consolidation of the acoustic CS fear response only immediately after acquisition and not 24-h post-acquisition. The present findings help to elucidate the role of the NBM in memory consolidation and better define the neural circuits involved in fear memories.

The histamine H3-receptor inverse agonist Pitolisant improves fear memory in mice

“…Procognitive effects are observed in the fear conditioning paradigm when H 3 R of the BLA or the hippocampus are activated rather than blocked [32][33][34], an observation opposite to the results obtained after systemic injections of thioperamide or Pitolisant (Charlier and Tirelli [14]; present results). Many studies have shown that the NBM plays a central role in memory consolidation of information acquired in the fear conditioning task [6,35]. Benetti et al [36] found that thioperamide microinjected into the NBM improves consolidation of contextual fear memory in rats.…”

“…Histaminergic neurons send their fibers to almost all brain areas including the amygdala and the nucleus basalis magnocellularis (NBM), two cortical areas involved in memory processes essential to consolidate adverse events [5,6]. Histamine is synthesized from l-histidine by the enzyme histidine decarboxylase (HDC) and its effects are mediated by four histamine receptors in the brain: the histamine H 1 , H 2 , H 3 and H 4 receptors (H 1 R, H 2 R, H 3 R and H 4 R).…”

Brain sites involved in fear memory reconsolidation and extinction of rodents

“…In our laboratory the nucleus basalis magnocellularis (NBM) role 758 in fear memory reconsolidation was studied. This interest is derived 759 from our previous demonstration that this neural site, which con-760 stitutes the main source of cholinergic projections to the cortex and 761 amygdala, is involved in the consolidation of both auditory and con-762 textual engrams in fear conditioning (Baldi et al, 2007). We found 763 that the NBM is not involved in the post-reactivation phase of fear 764 memories.…”

Generalized fear after acute stress is caused by change in neuronal cotransmitter identity

“…Pairing of an unconditioned stimulus (US; foot shock) and the conditioning stimulus (CS) leads to conditioned fear when testing occurs later in the same context (context A) (2,13,14). Increasing the intensity of the US produces fear generalization even when testing occurs later in a new context (context B), with different shape, size, texture, and color (14)(15)(16). We validated these findings by testing the effects of a single weak foot shock (0.5 mA, 1 s) and five strong (1.5 mA, 2 s) foot shocks on acquisition of conditioned and generalized fear in mice.…”