Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short-term memory task

Abstract

Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB) can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for 10-100 s. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM) impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM) had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.

Keywords: acetylcholine; delayed match-to-sample; olfaction; olfactory bulb; scopolamine.

Figure 1

Experimental setup for the delayed match-to-sample task. (A) At the start of a trial, the rat was presented with a ceramic dish containing odorized bedding. (B) After allowing for 10–15 s of investigation, the sample odor dish was removed and a delay period (ranging from 0 s to 10 min) was imposed. (C) At the end of the delay period, the divider was raised and the rat moved to the test chamber and had to discriminate between a dish containing the matching odor (rewarded) and one containing a non-matching odor (unrewarded). A trial was counted as correct if the rat initiated digging in the matching odor dish first.

Figure 2

Histological verification of cannula placement. Coronal section through the OB illustrating placement of guide cannula and infusion needle. The arrowhead points to a cannula track in the right OB. Double headed arrow is 1 mm.

Figure 3

Performance on the baseline delayed match-to-sample. Percent correct performance as a function of delay, averaged across subjects (n = 6). Error bars indicate ±1 SEM. Asterisks indicates significant differences of ^*P < 0.05 and ^**P < 0.001 from performance obtained with a 0 s delay (baseline memory test).

Figure 4

Effect of blocking bulbar muscarinic receptors on delayed match-to-sample. Percent correct performance for the baseline (0 s delay) and short-term (120 s delay) memory tests after saline or scopolamine (7.6, 22.5, and 38 mM) infusion into the olfactory bulb. Error bars indicate ±1 SEM. Asterisks indicate significant differences of ^*P < 0.05 and ^**P < 0.005 relative to saline controls.