PT  - JOURNAL ARTICLE
AU  - Laura A. Bradfield
AU  - Bernard W. Balleine
TI  - Thalamic Control of Dorsomedial Striatum Regulates Internal State to Guide Goal-Directed Action Selection
AID  - 10.1523/JNEUROSCI.3860-16.2017
DP  - 2017 Mar 29
TA  - The Journal of Neuroscience
PG  - 3721--3733
VI  - 37
IP  - 13
4099  - http://www.jneurosci.org/content/37/13/3721.short
4100  - http://www.jneurosci.org/content/37/13/3721.full
SO  - J. Neurosci.2017 Mar 29; 37
AB  - We (Bradfield et al., 2013) have demonstrated previously that parafascicular thalamic nucleus (PF)-controlled neurons in the posterior dorsomedial striatum (pDMS) are critical for interlacing new and existing action–outcome contingencies to control goal-directed action. Based on these findings, it was suggested that animals with a dysfunctional PF–pDMS pathway might suffer a deficit in creating or retrieving internal contexts or “states” on which such information could become conditional. To assess this hypothesis more directly, rats were given a disconnection treatment using contralateral cytotoxic lesions of the PF and pDMS (Group CONTRA) or ipsilateral control lesions (Group IPSI) and trained to press a right and left lever for sucrose and pellet outcomes, after which these contingencies were reversed. The rats were then given an outcome devaluation test (all experiments) and a test of outcome-specific reinstatement (Experiments 1 and 3). We found that devaluation performance was intact for both groups after training of initial contingencies, but impaired for Group CONTRA after reversal. However, performance was restored by additional reversal training. Furthermore, when tested a second time after reversal training, rats in both groups demonstrated responding in accordance with the original contingencies, providing direct evidence of modulation of action selection by state. Finally, we found that external context could substitute for internal state and so could rescue responding in Group CONTRA, but only in the reinstatement test. Together, these findings suggest that animals use internal state information to guide action selection and that this information is modulated by the PF–pDMS pathway.SIGNIFICANCE STATEMENT Individuals with Parkinson's disease dementia often suffer a characteristic deficit in “cognitive flexibility.” It has been suggested that neurodegeneration in the pathway between the centromedian/parafascicular thalalmic nucleus (PF) and striatum might underlie such deficits (Smith et al., 2014). In rats, we have similarly observed that a functional disconnection of the PF–posterior dorsomedial striatal pathway produces a specific impairment in the ability to alter goal-directed actions (Bradfield et al., 2013). It was suggested that this impairment could be a result of a deficit in state modulation. Here, we present four experiments that provide evidence for this hypothesis and suggest several ways (e.g., extended practice, providing external cues) in which this state modulation can be rescued.