Dorsomedial and dorsolateral striatum exhibit distinct phasic neuronal activity during alcohol self‐administration in rats

Abstract

The development of alcoholism may involve a shift from goal-directed to habitual drinking. These action control systems are distinct in the dorsal striatum, with the dorsomedial striatum (DMS) important for goal-directed behavior and the dorsolateral striatum (DLS) required for habit formation. Goal-directed behavior can be modeled in rats with a fixed ratio (FR) reinforcement schedule, while a variable interval (VI) schedule promotes habitual behavior (e.g., insensitivity to contingency degradation). Using extracellular recordings from chronically implanted electrodes, we investigated how DMS and DLS neurons encoded lever-press responses and conditioned cues during operant alcohol self-administration in these two models. In rats self-administering 10% alcohol on a FR schedule, the DMS neuronal population showed increased firing at the onset of start-of-session stimuli. During self-administration, the most prominent phasic firing patterns in the DMS occurred at the time of reinforcement and reinforcement-associated cues, while the most prominent phasic activity in the DLS surrounded the lever response. Neural recordings from an additional cohort of rats trained on a VI schedule revealed a similar pattern of results; however, phasic changes in firing were smaller and differences between the medial and lateral dorsal striatum were less marked. In summary, the DMS and DLS exhibited overlapping but specialized phasic firing patterns: DMS excitations were typically time-locked to reinforcement, while DLS excitations were generally associated with lever responses. Furthermore, the regional specificities and magnitudes of phasic firing differed between reinforcement schedules, which may reflect differences in behavioral flexibility, reward expectancy and the action sequences required to procure reinforcement.

Erratum: Repeated Binge-Like Ethanol Drinking Alters Ethanol Drinking Patterns and Depresses Striatal GABAergic Transmission

“…Thus, we examined GABAergic and glutamatergic synaptic transmission in the striatum, a brain region known to be affected by ethanol exposure and self-administration (Wang et al, 2010;Cuzon Carlson et al, 2011;Cui et al, 2013;Depoy et al, 2013;Fanelli et al, 2013). Electrophysiological analyses showed that inhibitory GABAergic synapses are depressed following the DID treatment in both striatal subregions, DLS and DMS.…”

“…Specifically, the dorsolateral (DLS) and dorsomedial striatum (DMS) are implicated in addiction (Koob and Volkow, 2010;Volkow et al, 2012). The dorsal striatum region is involved in ethanol drinking and it is the site of ethanol neuroadaptations (Wang et al, 2010;Cuzon Carlson et al, 2011;Cui et al, 2013;Depoy et al, 2013;Fanelli et al, 2013). Recently, we reported that non-human primates with 42 years of intermittent ethanol drinking exhibited a higher density of dendritic spines and altered putamen glutamatergic and GABAergic neurotransmission, a region homologous to the mouse DLS .…”

Translational Research on Habit and Alcohol

“…The random or variable interval schedules of reinforcement are based on a low perceived response-reward contingency, as an operant response produces a reward only after a variable time-interval elapses [e.g. 1, 53, 54–57]. Under random or variable interval reinforcement schedules, performance is less dependent on predictable reward delivery, and thus operant responding persists longer under extinction conditions or contingency changes.…”

“…Lesion and inactivation experiments have identified the dorsolateral striatum as a key site for habit formation and maintenance in rodents [20, 77, 78]. Further, electrophysiological studies have found distinct firing patterns of neurons in the dorsolateral striatum during habit-like reward seeking as opposed to goal-directed seeking [53, 54]. The primate homolog of the rodent dorsolateral striatum, the putamen, plays a similar critical role in habitual or automatic behavior [45, 47–49].…”

“…Drinking initiation is often considered to be a goal-directed behavior targeting a variety of primary aims, such as facilitating social interaction, feeling drug-induced euphoria, or coping with stress, anxiety or depression [142, 143]. However, animal studies demonstrate that chronic or persistent alcohol drinking, sometimes even at small doses, can develop into inflexible habitual alcohol seeking [53, 57, 144]. Once formed, habits are hard to break; therefore, the transition from occasional goal-directed to habitual alcohol seeking, and perhaps drinking, is an important aspect in our understanding the development of AUDs [145].…”