Involvement of the dorsomedial striatum in behavioral flexibility: role of muscarinic cholinergic receptors

Michael E. Ragozzino , Jane Jih, Arianna Tzavos

Brain Research (2002)

Doi: 10.1016/S0006-8993(02)03287-0

Brief summary: Ragozzino and colleagues found that blockade or inactivation of the cholinergic muscarinic receptors in dorsomedial striatum (DMS) could impair the response reversal learning, but had no effects on the initial acquisition. The impairment was caused by the deficit in learning the new behavioral strategy, but not because of the perseveration of previously learned strategy.

How the first attempt happened? Or what triggered the authors to start this study? After all, before this study, no one had associated acetylcholine in striatum with reversal learning? With the question keeping in mind, I go through their previous papers and, find that this study was an ongoing work of a series of lesion studies from Raymond Kesner‘s lab (Ragozzino’s advisor during post-doc). They lesioned the medial prefrontal cortex (mPFC) (Involvement of the Prelimbic–Infralimbic Areas of the RodentPrefrontal Cortex in Behavioral Flexibility for Place andResponse Learning, 1999, JNS) and found that the performance during extra-dimensional shift (between place discrimination and response discrimination in cross maze) was impaired, while the initial acquisition and intra-dimensional reversal learning (within place discrimination or response discrimination) performance was intact. Because mPFC has strong connections with DMS, so they lesioned DMS and also observed that rat shown deficits in the extra-dimensional shift (Role of the Dorsomedial Striatum in Behavioral Flexibility for Responseand Visual Cue Discrimination Learning, 2002, Behavioral Neuroscience). Then how they conceived to test the acetylcholine receptors? I think this idea should be emerged naturally. Because they already known DMS is important, and their are two major modulators in DMS: dopamine and acetylcholine. Dopamine is a star molecule at the time, so they tried to test the acetylcholine instead.

We can infer that this study was driven by their sensitive perception of the cutting-edge progress in the field at the time. The lessons are: be sensitive about the boundary of the knowings, and put forward the boundary a small step at a time. After all, who can tell what products will be produced ten years later by the ‘miner’ progress judged from the short perspective.