Evidence from human fMRI studies has been consistent with this hypothesis, demonstrating that novelty at encoding elicits responses in SN/VTA that are associated with beneficial effects on subsequent memory (Wittmann et al., 2007; Schott et al., 2004; Krebs et al., 2009). Importantly, as noted above, SN/VTA cells also provide dopaminergic input into the striatum (Figure 1B) where the information they convey about expected reward and other behaviorally relevant features of an input, like novelty, can influence learning, action selection, and decision-making. For example, when harvesting reward in a stochastic environment, strategically directing

exploratory behavior to novel items has the potential to glean the most new information about that environment (Kakade and Dayan, selleck 2002; Daw et al., 2006; Frank et al., 2009; Badre et al., 2012). Indeed, striatal novelty responses have been specifically associated with novelty-driven choices during economic decisions (Guitart-Masip et al., 2010; Wittmann et al., 2008; Krebs et al., 2009). Moreover, many studies citing SN/VTA activation in response to novelty, also report responses to novel greater than familiar items in the striatum (e.g., Bunzeck and Düzel, 2006; Guitart-Masip et al., 2010). Notably, AZD8055 ic50 these activations fall in close proximity to those associated

with retrieval success (Figure 2). Thus, considered together with retrieval success effects, the evidence for novelty responses in the striatum argues against obligatory coding of item oldness in striatum as a consequence of episodic retrieval. Rather, striatal responses to episodic memory signals are likely modulated depending on the adaptive significance of “oldness” or “newness” to the animal’s current actions and Phosphatidylinositol diacylglycerol-lyase desired outcomes. Two recent findings provide support for this hypothesis.

Bunzeck et al. (2010) showed that responses in the striatum are scaled adaptively based on expectations of the relative novelty and oldness of items in the environment. Han et al. (2010) more directly manipulated the goal relevance of item novelty versus oldness and revealed a similar dynamic flexibility in striatal responses. Specifically, retrieval goals were manipulated by associating either “old” or “new” responses with potential monetary reward. When “old” responses were incentivized, participants earned money for correct old responses (hits) and lost money for incorrect old responses (false alarm) and neither gained nor lost money for “new” responses (and vice versa when “new” was incentivized). Activity in the caudate tracked the incentivized response independent of whether the item was studied or novel (Figure 3).