Modulation of spatial cognition in adult rats by biological sex, gonadal steroids, affective conditions, and cholinergic neurotransmision
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Description
In rodents, spatial learning and memory is contingent upon examining the relationships between cues in a three-dimensional environment. Although multiple brain structures are involved, the hippocampus serves as the epicenter of spatial information processing. Alternatively, on certain dual-solution navigational tasks, reliance on either a hippocampus-dependent place learning strategy or striatum-dependent response or stimulus-response learning strategy can be used to locate a goal. However, factors that dysregulate hippocampus function result in both poorer performance on spatial tasks and a shift toward adopting striatum-dependent learning strategies. Because gonadal hormones, affective states, and cholinergic neurotransmission modulate hippocampus function, the goal of the current study was to gain a greater understanding of how these factors impact spatial cognition and learning strategy preference. Relative to female rats, male rats performed better during the learning phase of a dual-solution learning task and exhibited a greater preference for a place learning strategy. Notably, in female rats, ovarian hormones modulated both spatial cognition and learning strategy preference, effects that likely involved activation of the putative estrogen membrane receptor GPR30. Alternatively, in male rats, spatial learning and memory, but not the preference for a place learning strategy, was attenuated by the removal of testicular hormones, an effect abrogated by testosterone treatment. Furthermore, for male rats, higher levels of trait anxiety and exposure to multiple reminders of a stressor were associated with a greater reliance on striatum-based learning strategies. From a neurochemical standpoint, the preference for a striatum-based learning strategy in male rats was associated with lower levels of choline acetyltransferase in the hippocampus, which indicates that the cholinergic system is involved in learning strategy preference. However, antagonism of muscarinic receptors in the hippocampus caused a learning impairment in male rats on the same dual-solution learning task, which indicates that cholinergic neurotransmission in the hippocampus is necessary for learning a task in which the striatum also provides solution. Identifying factors such as stress exposure or gonadal hormones that alter the cholinergic integrity of the hippocampus is an important step in generating therapeutic strategies designed to treat individuals suffering from cogniti