Unraveling the Role of the Hippocampus in Reversal Learning

Abstract

Research in reversal learning has mainly focused on the functional role of dopamine and striatal structures in driving behavior on the basis of classic reinforcement learning mechanisms. However, recent evidence indicates that, beyond classic reinforcement learning adaptations, individuals may also learn the inherent task structure and anticipate the occurrence of reversals. A candidate structure to support such task representation is the hippocampus, which might create a flexible representation of the environment that can be adaptively applied to goaldirected behavior. To investigate the functional role of the hippocampus in the implementation of anticipatory strategies in reversal learning, we first studied, in 20 healthy individuals (11 women), whether the gray matter anatomy and volume of the hippocampus were related to anticipatory strategies in a reversal learning task. Second, we tested 20 refractory temporal lobe epileptic patients (11 women) with unilateral hippocampal sclerosis, who served as a hippocampal lesion model. Our results indicate that healthy participants were able to learn the task structure and useittoguidetheirbehaviorandoptimizetheirperformance.Participants'abilitytoadoptanticipatorystrategiescorrelatedwiththegraymatter volume of the hippocampus. In contrast, hippocampal patients were unable to grasp the higher-order structure of the task with the same success than controls. Present results indicate that the hippocampus is necessary to respond in an appropriately flexible manner to high-order environments, and disruptions in this structure can render behavior habitual and inflexible.

Accelerated decline in cognition in a mouse model of increased oxidative stress

“…Thus, our observation that the high levels of oxidative stress observed in the hippocampus of Sod1KO mice are associated with a decline in cognition supports the concept that oxidative stress has an important and primary role in the agerelated decline in cognition. In our study, Sod1KO mice exhibited a deficit in reversal learning, not initial discrimination, that is indicative of a dysfunction in the coordinated actions of brain regions such as the hippocampus, orbitofrontal cortex, dorsal striatum, and amygdala (Vilà-Balló et al 2017, Ragozzino 2007Tait and Brown 2007;Bissonette and Powell, 2012;Floresco and Jentsch 2011). In Sprague-Dawley rats, reversal learning assessed using the Morris water maze is impaired by blocking hippocampal long-term depression (LTD), suggesting hippocampal LTD as an integral component of extinction of a learned task and acquisition of new information (Dong et al 2013).…”

Belief state representation in the dopamine system

“…Another potential substrate for belief state inference is the hippocampus. It has been proposed to support structure learning 46 – 50 , which would allow mice to infer the latent causes governing the structure of a task, such as learning the two-state representation despite ambiguous predictive cues. A recent study found that dopamine neurons alter their responses based on changes in sensory features of reward 51 .…”

The Effects of P-Hydroxycinnamic Acid in Ameliorating Spatial Learning and Flexibility Deficits in Rats with Chronic Cerebral Hypoperfusion

“…The CA1 hippocampal place cells acquire spatial location, with entorhinal grid cells also participating (O'Keefe 1993;O'Keefe & Conway 1978;O'Keefe & Dostrovsky 1971). In reversal learning, the neural basis involves the cortical regions, orbitofrontal cortex (OFC), striatal, amygdala (Izquierdo et al 2016) and hippocampus (Vila-Ballo et al 2017). It has been shown that CA1 and CA3 cells firing respond differently to familiar versus changed environments (Bahar et al 2011), and the within-hippocampal circuit (CA1, 3 and DG) contributes differently to distinct aspects of spatial cognition.…”