The Parafascicular Thalamic Nucleus Concomitantly Influences Behavioral Flexibility and Dorsomedial striatum Acetylcholine Output in Rats

Holden D. Brown, Phillip M. Baker, and Michael E. Ragozzino

The Journal of Neuroscience (2010)

DOI:10.1523/JNEUROSCI.2167-10.2010

Brief summary: in this study, Brown and colleagues shown that the inactivation of parafascilar thalamic nucleus (Pf) with GABA agonists impaired the place reversal learning performance in a cross maze in a dose-dependent manner. This inactivation also decreased the acetylcholine efflux in anterior dorsomedial striatum. 

It’s the first attempt to test the functional role of Pf with the reversal learning paradigm. Experiments were performed within a four-arm cross maze. Two arms were used as the starting point, the other two as the goal arms. One of the goal arm was baited with food. During each trial, one of the two start arm was randomly picked, while the other was blocked  with a plastic board. During the initial acquisition learning, one goal arm was randomly chosen as the baited one. Rats should learn to correctly choose that arm to get reward. After the acquisition learning, the baited arm was switched to the previously un-baited arm in the following day. This is the reversal learning phase. By injecting the GABA agonists within Pf at different dose, the authors found that high-dose agonist could impaired the reversal learning, but did not significantly affect the initial learning. Concomitantly, the drug application at a higher dose also decreased the efflux of acetylcholine (measured with HPLC/electrochemical detection) in the anterior dorsomedial striatum during reversal learning. The results implied that the cholinergic interneurons may facilitate reversal learning by increasing its efflux. 

The experiments are quite simple. The challenge resides in how the authors conceived to use the reversal learning paradigm to test the role of Pf? According to the Introduction, we can notice that several pieces of clues may be helpful: 1. ‘CM–Pf neurons exhibit correlated firing to unexpected stimuli or stimulirequiring an unpredicted response (Minamimoto and Kimura,2002)’; 2. ‘Pf has reciprocal connections with the basal ganglia, a region importantfor response selection; 3. ‘Electrical stimulation of the primate CM alters firing patterns of striatal neurons,including putative cholinergic interneurons’; 4. ‘the dorsomedial striatum is critical when conditions require inhibition of one learned choice pattern and shift to a new or different choice pattern (Pisa and Cyr,1990,Ragozzino et al., 2002a,b, 2004, 2009; Nicolle and Baxter, 2003;O’Neill and Brown, 2007). This type of behavioral flexibility isrequired in reversal learning tests’; 5. ‘dorsomedial striatum acetylcholine (ACh) efflux selectively increases during reversal learning, whereas blockade of the ACh increase impairs reversal learning (Palencia and Ragozzino, 2006; Ragozzino et al.,2009)’. At last, they inferred that ‘One possibility, therefore, is that excitatory input from the Pf stimulates cholinergic neuronal activity in the dorsomedial striatum to facilitate behavioral flexibility’. 

We can notice that there are many related studies published from the same lab recently. They made the choice (using place reversal learning test) by considering/combining multiple small findings. This study appropriately instantiated the accumulated nature of scientific progress. Most studies are piece-by-piece findings. The milestones are the catalytic combinations of these pieces. However, this study is not such a milestone, but only a piece of small finding.