Learning, memory and consolidation mechanisms for behavioral control in hierarchically organized cortico-basal ganglia systems

This article aims to provide a synthesis on the question how brain structures cooperate to accomplish hierarchically organized behaviors, characterized by low-level, habitual routines nested in larger sequences of planned, goal-directed behavior. The functioning of a connected set of brain structures-prefrontal cortex, hippocampus, striatum, and dopaminergic mesencephalon-is reviewed in relation to two important distinctions: (a) goal-directed as opposed to habitual behavior and (b) model-based and model-free learning. Recent evidence indicates that the orbitomedial prefrontal cortices not only subserve goal-directed behavior and model-based learning, but also code the "landscape" (task space) of behaviorally relevant variables. While the hippocampus stands out for its role in coding and memorizing world state representations, it is argued to function in model-based learning but is not required for coding of action-outcome contingencies, illustrating that goal-directed behavior is not congruent with model-based learning. While the dorsolateral and dorsomedial striatum largely conform to the dichotomy between habitual versus goal-directed behavior, ventral striatal functions go beyond this distinction. Next, we contextualize findings on coding of reward-prediction errors by ventral tegmental dopamine neurons to suggest a broader role of mesencephalic dopamine cells, viz. in behavioral reactivity and signaling unexpected sensory changes. We hypothesize that goal-directed behavior is hierarchically organized in interconnected cortico-basal ganglia loops, where a limbic-affective prefrontal-ventral striatal loop controls action selection in a dorsomedial prefrontal-striatal loop, which in turn regulates activity in sensorimotor-dorsolateral striatal circuits. This structure for behavioral organization requires alignment with mechanisms for memory formation and consolidation. We propose that frontal corticothalamic circuits form a high-level loop for memory processing that initiates and temporally organizes nested activities in lower-level loops, including the hippocampus and the ripple-associated replay it generates. The evidence on hierarchically organized behavior converges with that on consolidation mechanisms in suggesting a frontal-to-caudal directionality in processing control

Developmental changes in short-term plasticity at the rat calyx of Held synapse

The calyx of Held synapse of the medial nucleus of the trapezoid body functions as a relay synapse in the auditory brainstem. In vivo recordings have shown that this synapse displays low release probability and that the average size of synaptic potentials does not depend on recent history. We used a ventral approach to make in vivo extracellular recordings from the calyx of Held synapse in rats aged postnatal day 4 (P4) to P29 to study the developmental changes that allow this synapse to function as a relay. Between P4 and P8, we observed evidence for the presence of large short-term depression, which was counteracted by short-term facilitation at short intervals. Major changes occurred in the last few days before the onset of hearing for air-borne sounds, which happened at P13. The bursting pattern changed into a primary-like pattern, the amount of depression and facilitation decreased strongly, and the decay of facilitation became much faster. Whereas short-term plasticity was the most important cause of variability in the size of the synaptic potentials in immature animals, its role became minor around hearing onset and afterward. Similar developmental changes were observed during stimulation ex

Corticosterone impairs flexible adjustment of spatial navigation in an associative place-reward learning task

Cognitive challenges are often accompanied by a discharge of stress hormones, which in turn modulate multiple brain areas. Among these, the medial temporal lobe and the prefrontal cortex are critically involved in high-order cognitive functions such as learning, memory, and decision-making. Previous studies assessing the effects of corticosterone on spatial memory found an increase or a decrease in performance depending on the timing of stress hormone discharge relative to the behavioral task. Most of these studies, however, made use of aversively motivated behaviors, whereas less is known about corticosteroid effects on flexible learning during reward-driven spatial navigation. To study how corticosterone modulates flexible spatial learning, we tested rats on a place-reward association task where hormone treatment was administered immediately after a session presenting a change in reward locations. The corticosterone-treated group showed delayed learning during the initial sessions and suboptimal memory consolidation throughout testing. Repeated training on the novel reward positions improved performance and eliminated differences from the control group. We conclude that a marked increase in plasma corticosterone levels immediately after training impairs the flexible formation of new place-reward associations