Cholinergic modulation of the hippocampus during encoding and retrieval of tone/shock-induced fear conditioning

Abstract

We investigated the role of acetylcholine (ACh) during encoding and retrieval of tone/shock-induced fear conditioning with the aim of testing Hasselmo's cholinergic modulation model of encoding and retrieval using a task sensitive to hippocampal disruption. Lesions of the hippocampus impair acquisition and retention of contextual conditioning with no effect on tone conditioning. Cholinergic antagonists also impair acquisition of contextual conditioning. Saline, scopolamine, or physostigmine was administered directly into the CA3 subregion of the hippocampus 10 min before rats were trained on a tone/shock-induced fear conditioning paradigm. Freezing behavior was used as the measure of learning. The scopolamine group froze significantly less during acquisition to the context relative to controls. The scopolamine group also froze less to the context test administered 24 h posttraining. A finer analysis of the data revealed that scopolamine disrupted encoding but not retrieval. The physostigmine group initially froze less during acquisition to the context, although this was not significantly different from controls. During the context test, the physostigmine group froze less initially but quickly matched the freezing levels of controls. A finer analysis of the data indicated that physostigmine disrupted retrieval but not encoding. These results suggest that increased ACh levels are necessary for encoding new spatial contexts, whereas decreased ACh levels are necessary for retrieving previously learned spatial contexts.

Figure 1

Histological verification of cannulae placement (n = 20) in the CA3 subregion and approximate spread of drug assessed by dye (Chicago blue) infusion indicated by circular cross-shaded area. Each dot represents the approximate point at which a cannula was positioned for each animal.

Figure 2

Percent freezing during the acquisition of contextual fear following the preacquisition period on Day 1. Data are presented as a function of trials. Note that the scopolamine group froze significantly less than the saline group.

Figure 3

Encoding index for contextual conditioning. Note that the scopolamine group displayed little encoding compared to either the saline or physostigmine group. (*P < 0.05 in comparison to the control group).

Figure 4

Percent freezing during the context retention test given 24 h postconditioning. Data are presented as a function of time. Note that the scopolamine group froze significantly less than the saline group.

Figure 5

Retrieval index for contextual conditioning. Note that the physostigmine group was impaired during retrieval compared to either the saline or scopolamine group. (*P < 0.05 in comparison to the control group)

Figure 6

Percent freezing during the cue retention test given 48 h postconditioning. Data are presented as a function of time. Note no significant difference among groups.