Cholinergic Interneurons Use Orbitofrontal Input to Track Beliefs about Current State

Abstract

When conditions change, organisms need to learn about the changed conditions without interfering with what they already know. To do so, they can assign the new learning to a new "state" and the old learning to a previous state. This state assignment is fundamental to behavioral flexibility. Cholinergic interneurons (CINs) in the dorsomedial striatum (DMS) are necessary for associative information to be compartmentalized in this way, but the mechanism by which they do so is unknown. Here we addressed this question by recording putative CINs from the DMS in rats performing a task consisting of a series of trial blocks, or states, that required the recall and application of contradictory associative information. We found that individual CINs in the DMS represented the current state throughout each trial. These state correlates were not observed in dorsolateral striatal CINs recorded in the same rats. Notably, DMS CIN ensembles tracked rats' beliefs about the current state such that, when states were miscoded, rats tended to make suboptimal choices reflecting the miscoding. State information held by the DMS CINs also depended completely on the orbitofrontal cortex, an area that has been proposed to signal environmental states. These results suggest that CINs set the stage for recalling associative information relevant to the current environment by maintaining a real-time representation of the current state. Such a role has novel implications for understanding the neural basis of a variety of psychiatric diseases, such as addiction or anxiety disorders, in which patients generalize inappropriately (or fail to generalize) between different environments.

Suppression of Ventral Hippocampal Output Impairs Integrated Orbitofrontal Encoding of Task Structure

“…And more recent work has suggested the OFC might also utilize or perhaps even encode these relationships (Bradfield et al, 2015; Saez et al, 2015; Schuck et al, 2016; Stalnaker et al, 2016; Wilson et al, 2014). For example, associative event-driven firing in the OFC is often specific to the cue-reward combinations appropriate for a given context or set of trials (Saez et al, 2015; Schoenbaum et al, 1999; Thorpe et al, 1983), and in one particularly nice set of parallel studies, ensembles of neurons in the OFC (Farovik et al, 2015) and the hippocampus (Komorowski et al, 2013; McKenzie et al, 2014; McKenzie et al, 2016) were found to encode a hierarchy of feature representations in rats performing a decision making task, with neurons in each area encoding abstract aspects of the task, such as the context-dependent linkages between odor cues and reward.…”

Effects of inference on dopaminergic prediction errors depend on orbitofrontal processing.

“…Indeed, the influence of such state representations may be ubiquitous once one begins to look for it. Event-related firing the OFC as well as other prefrontal areas and even amygdala is influenced by context or state defined as trial blocks with different reward contingencies (Saez et al, 2015; T A Stalnaker et al, 2014), and cholinergic interneurons in the dorsal striatum provide an OFC-dependent state correlate that distinguishes such different blocks of trials (Stalnaker et al, 2016). …”

Excitatory extrinsic afferents to striatal interneurons and interactions with striatal microcircuitry

“…Recording of CINs in rats performing a behavioral task consisting of several trial blocks referred as ‘state’ which requires the recall of the current state and the learning of changed conditions have shown that dorsomedial but not dorsolateral striatal CINs are essential for the animal to keep track of the current behavioral trial or state. This state information is dependent on orbitofrontal cortex input to CINs (Stalnaker et al ., ). Those results are consistent with observations showing involvement of CINs in flexible behaviors and in integrating new learning (Ragozzino et al ., ; Bradfield et al ., ; Aoki et al ., ).…”