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.

Figure 1.

Injection sites in nucleus basalis magnocellularis (NBM) (arrows indicate end of needle tracks).

Figure 2.

Freezing reaction to fear conditioning training. Mean ± SEM freezing as percentage of total time in the 2-min period after last shock during fear conditioning acquisition training. (For details, see Materials and Methods.)

Figure 3.

Effects of NBM bilateral TTX inactivation at increasing post-acquisition delays (0.25, 24, and 48 h) on fear conditioning to context and acoustic CS. Black columns are TTX-injected groups; white columns are saline-injected groups. Mean ± SEM freezing as percentage of total 3-min period during retention testing (performed 72 and 96 h after TTX or saline administration) in the conditioning apparatus without acoustic stimulation (context) and in the other apparatus with acoustic stimulation (CS). *P < 0.05, **P < 0.01; statistically significant differences between treated and respective control groups.

Figure 4.

Absence of generalization in rats after TTX and saline injection in the NBM. Mean ± SEM freezing as percentage of total time in the first 3-min period in the new context without acoustic CS presentation during retention testing. (For details, see Materials and Methods.)

Figure 5.

Absence of effects of NBM unilateral TTX inactivation performed immediately (0.25 h) after acquisition training. For explanation, see Fig. 3.