, 2009). Importantly, whereas the levels of ERK1/2 activation in the pDMS did not differ between Sham and Ipsi groups, F (1, 21) = 0.414, p = 0.527, a significant increase of activated MSNs was observed in the group Contra, F (1, 21) = 4.565, p = 0.045 (Figure 5E). Moreover, we detected very few phospho-ERK1/2 neurons in the DLS (Figure 5F), in line with the more critical role of the pDMS relative to the DLS in the context of goal-directed action (Shiflett et al., 2010). These data suggest that the expected decrease of Pf glutamatergic input to the pDMS had a direct effect

on the activity of CINs but did not produce a similar effect on MSNs. Rather, it resulted in an increase in MSN activity, most likely due to the loss of the general inhibitory effect of CINs on striatal MSNs. The effect of Pf lesions on MSN activation reported here supports the recently described neuromodulatory nature of

these specific projections (Ellender et al., 2013) www.selleckchem.com/products/bmn-673.html and points to the importance of the Pf-CIN synapses in controlling striatal processes (Ding et al., 2010; Threlfell et al., 2012). In a separate group of rats, we investigated whether the impairments we observed after Pf-pDMS disconnection were specific to the posterior DMS, or whether disconnection of the Pf from anterior DMS (aDMS) would produce a similar effect. It selleck chemicals is well known that the Pf projects to both the aDMS and pDMS (Deschênes et al., 1996), and a previous study observed an increase in acetylcholine in aDMS as rats learned new stimulus-outcome associations in a place task (Brown et al., 2010). The Pf-aDMS pathway, however, appears not to

be required to learn new action-outcome contingencies; we found that rats with contralateral Pf and aDMS lesions showed intact initial learning (Figure S1) and, unlike the pDMS disconnection, also showed intact outcome devaluation (Figure 4G) and outcome-specific reinstatement (Figure S1) after the reversal of the action-outcome contingencies (Figure 4G; Figure S1). Statistical analysis showed that the lesion had no effect on reversal training (F < 1) and, on test, that there was an effect of devaluation (nondevalued > devalued), F (1, 13) = 8.69, p = 0.011, but no group × devaluation interaction, F < 1. The results of this experiment suggest, therefore, that the thalamostriatal pathway much connecting the Pf and aDMS does not play a role in either initial learning or the acquisition of new goal-directed actions and confirm, therefore, that the findings following disconnection of the Pf-pDMS pathway on new learning are specific to that pathway. This is consistent with the argument that the Pf alters the functional role of cholinergic interneurons specifically in the pDMS to enable the encoding of new action-outcome associations. The observed effects of Pf lesion on CIN function in pDMS suggests that the observed behavioral effects of bilateral Pf and contralateral Pf-pDMS lesions are most likely regulated by alterations in CIN function in pDMS.