Abstract
The striatum plays a key role in motor learning. Striatal function depends strongly on dopaminergic neurotransmission, but little is known about neuroadaptions of the dopamine system during striatal learning. Using an established task that allows differentiation between acquisition and consolidation of motor learning, we here investigate D1 and D2-like receptor binding and transcriptional levels after initial and long-term training of mice. We found profound reduction in D1 binding within the dorsomedial striatum (DMS) after the first training session on the accelerated rotarod and a progressive reduction in D2-like binding within the dorsolateral striatum (DLS) after extended training. Given that similar phase- and region-specific striatal neuroadaptations have been found also during learning of complex procedural tasks including habit formation and automatic responding, the here observed neurochemical alterations are important for our understanding of neuropsychiatric disorders that show a dysbalance in the function of striatal circuits, such as in addictive behaviors.
Highlights
The ability to optimize learned motor sequences is essential for survival
Gene expression and ligand binding in relevant brain areas (i.e., Accumbens nucleus core (AcbC), accumbens nucleus shell (AcbS), dorsolateral striatum (DLS), dorsomedial striatum (DMS), substantia nigra pars compacta (SNC), substantia nigra pars reticulata (SNR), olfactory tubercle (Tu), ventral tegmental area (VTA)) were tested in naïve control animals and in groups that had undergone 1 day or 8 days of rotarod training
We found a down regulation of D1 receptors in the DMS after rotarod training that was most pronounced on day 1, i.e., during the acquisition phase (Oneway ANOVA for effect of training: F(2,11) = 15.5, p < 0.001; post hoc tests: early vs. control p < 0.001, late vs. control p > 0.05, Figure 2C) while D1 binding in the DLS was not affected by the training (One-way ANOVA main effect of training: F(2,12) = 1.9, p = 0.2)
Summary
Most of our behaviors are organized in orderly structured actions consolidated into reflex-like response patterns that are largely resistant to interference (Shiffrin and Schneider, 1984; Dickinson, 1985). If the behavioral patterns are more complex and come occasionally to our attention, we think of them as habits. Running automatically through an action sequence frees our mind for other tasks that require attention. Such perfectionism has an important down side: it is difficult to overcome. After a smoker has gone through the same sequence of events many thousand times, he or she is often not aware of lightening a cigarette. A distinct cue may have triggered the event independent from any desire. Maladaptive automated processes are seen as key components in the development of pathological behaviors including addictive disorders (Everitt and Robbins, 2005)
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