Cell-type dependent selectivity of CCK2R signaling (WP3679)

This pathway is based on Figure 7 of "Cell-Type Specific CCK2 Receptor Signaling Underlies the Cholecystokinin-Mediated Selective Excitation of Hippocampal Parvalbumin-Positive Fast-Spiking Basket Cells."(See Bibliography).The neuropeptide cholecystokinin (CCK) acts through its receptor CCK2R to achieve largely different functions in different types of cells. CCK, CCK2R, and CB1R have all been known to have substantial effects on anxiety and other mood disorders, and the PV+ interneurons have also been shown to be involved i na variety of cognitive functions. However, In PV+ basket cells and CCK+ basket cells, the CCK2 receptor uses different pathways to exert different effects on the two types of basket cells. For CCK+ basket cells, CCK2 receptors in neighboring pyramidal cells act through the Gq pathway to form endocannabinoids, which, through the cannabinoid receptor type 1 on the CCK+ basket cell, inhibit the release of the neurotransmitter GABA. In contrast, for PV+ basket cells, CCK2 receptors act through the pertussin-toxin sensitive Gi pathway to regulate the intracellular Ca2+ through ryanodine receptors. This pathway ultimately leads to activation of a non-selective cationic conductance to depolarize the PV+ basket cells.

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