Involvement of the basolateral amygdala in muscarinic cholinergic modulation of extinction memory consolidation

Abstract

Previous studies have reported that drugs affecting neuromodulatory systems within the basolateral amygdala (BLA), including drugs affecting muscarinic cholinergic receptors, modulate the consolidation of many kinds of training, including contextual fear conditioning (CFC). The present experiments investigated the involvement of muscarinic cholinergic influences within the BLA in modulating the consolidation of CFC extinction memory. Male Sprague Dawley rats implanted with unilateral cannula aimed at the BLA were trained on a CFC task, using footshock stimulation, and 24 and 48 h later were given extinction training by replacing them in the apparatus without footshock. Following each extinction session they received intra-BLA infusions of the cholinergic agonist oxotremorine (10 ng). Immediate post-extinction BLA infusions significantly enhanced extinction but infusions administered 180 min after extinction training did not influence extinction. Thus the oxotremorine effects were time-dependent and not attributable to non-specific effects on retention performance. These findings provide evidence that, as previously found with original CFC learning, cholinergic activation within the BLA modulates the consolidation of CFC extinction.

Figure 1

A: Behavioral Procedure B: Freezing behavior in animals with right BLA infusions either of Vehicle (N=9) or OXO (N=15) administered immediately after extinction training. *p<0.05 compared with saline infused animals. Freezing behavior is expressed as mean ± SEM.

Figure 2

A: Behavioral Procedure B: Freezing behavior on the test day, in animals with right BLA infusions either of Vehicle or OXO in rats either given (Ext) or not given (N-Ext) extinction training. Veh-Ext, N=12; Veh N-Ext, N=9; Oxo-Ext, N=15; Oxo N-Ext, N= 9 **p<0.01 compared with saline infused animals. Freezing behavior is expressed as mean ± SEM.

Figure 3

A: Behavioral Procedure B: Freezing behavior in animals given a reinstatement session. Contextual fear memory was recovered after a mild footshock in animals where original memory was extinguished. This mild footshock per se did not induce a high level of freezing. **p<0.01 compared with the Vehicle (N=9) or Oxotremorine (N= 15) treated group. ## p<0.01 comparing test session with reinstatement session. Freezing behavior is expressed as mean ± SE.