Task-dependent function of striatal cholinergic interneurons in behavioural flexibility

Kana Okada, Kayo Nishizawa, Susumu Setogawa, Kouichi Hashimoto and Kazuto Kobayashi

European Journal of Neuroscience (2017)

doi:10.1111/ejn.13768

Brief summary: conflicting results were reported about the role of cholinergic interneurons (ChIs) in reversal learning tasks. What factors led to the different observations? In this study, Okada, et al, shown that the elimination of ChIs only impaired the reversal learning of response discrimination at short inter-trial-interval (ITI, 15s). While, with a10-min or 20-min ITI, the elimination enhanced the reversal learning of both the place and response discrimination. The results indicated a differential modulation effects of the ITI and the discrimination type on ChIs’ role in reversal learning.

Past pharmacological studies reported that the infusion of non-specific muscarinic receptor (one type of acetylcholine receptor) antagonist into dorsomedial striatum (DMS) impaired the reversal learning of responses/place discrimination (including one paper shared in 2021-07-08, Aging-Related Dysfunction of Striatal Cholinergic Interneurons Produces Conflict in Action Selection). Also, some reported no effects on reversal learning (Role of Striatal Cholinergic Interneurons in Set-Shifting inthe Rat, JNS, 2015). However, one previous study from the same lab of the current study (shared in 2021-07-07, Enhanced flexibility of place discrimination learning by targeting striatal cholinergic interneurons), shown that the elimination of ChIs enhanced the place reversal learning. How to reconcile those controversial findings? Through literature reading, the authors found that the spacing and the discrimination type may be critical modulators (Differential effects of massed and spaced training on place and response learning: A memory systems perspective, Behavioral Processes, 2015). So in the current study, they tested the hypotheses and indeed observed differential modulations on the reversal learning performance.

From one perspective, we can see the difficulty in reaching a consensus in behavioral studies, because there are many hidden factor which may affect the experimental results. From the other way, we can vividly observe how scientific investigators deal with controversies: proposing new hypothesis, and assessing it. From the outside, maybe time is the best arbitrator.