Abstract
To promote efficient explorative behaviors, subjects adaptively select spatial navigational strategies based on landmarks or a cognitive map. The hippocampus works alone or in conjunction with the dorsal striatum, both representing the neuronal underpinnings of the navigational strategies organized on the basis of different systems of spatial coordinate integration. The high expression of cannabinoid type 1 (CB1) receptors in structures related to spatial learning—such as the hippocampus, dorsal striatum and amygdala—renders the endocannabinoid system a critical target to study the balance between landmark- and cognitive map-based navigational strategies. In the present study, mice treated with the CB1-inverse agonist/antagonist AM251 or vehicle were trained on a Circular Hole Board, a task that could be solved through either navigational strategy. At the end of the behavioral testing, c-Fos immunoreactivity was evaluated in specific nuclei of the hippocampus, dorsal striatum and amygdala. AM251 treatment impaired spatial learning and modified the pattern of the performed navigational strategies as well as the c-Fos immunoreactivity in the hippocampus, dorsal striatum and amygdala. The present findings shed light on the involvement of CB1 receptors as part of the selection system of the navigational strategies implemented to efficiently solve the spatial problem.
Highlights
Spatial navigation is a complex ability based on the integration of sensory-motor, perceptual, cognitive and emotional processes [1,2]
Convergent evidence has proposed that the processes related to formation and maintenance of the implicit habits mainly rely on the intact functioning of the striatum [15,16,17,18], while allocentric spatial learning [19,20] and the formation of cognitive maps [21] critically depend on intact functioning of the hippocampus
Summing up: in VHL animals, the navigational strategy based on cognitive mapping determined a significant activation in all brain regions taken into account—the navigational strategy based on landmark determined a significant activation in CA1 and DMS, a significant de-activation in CA3, BLA and DLS, while no effect was found in dFocs-Faocstiavcattiivoantisoinns hiniphpiopcpaomcapmalpCalAC1Aa1ndanCdAC3Aa3ndanddendteantetagteyrus (DG) in comparison to the no-test condition; AM251 treatment blocked the activation in DMS that characterized the navigational strategy based on cognitive mapping
Summary
Spatial navigation is a complex ability based on the integration of sensory-motor, perceptual, cognitive and emotional processes [1,2]. Convergent evidence has proposed that the processes related to formation and maintenance of the implicit habits mainly rely on the intact functioning of the striatum [15,16,17,18], while allocentric spatial learning [19,20] and the formation of cognitive maps [21] critically depend on intact functioning of the hippocampus. These controversial findings indicate complex ECS effects on memory that cannot be merely defined as impairing or enhancing effects of endocannabinoid activation and deactivation Starting from these remarks, the present study focuses on the involvement of ECS in the selection of navigational strategies related to landmark or cognitive mapping.
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