Stressor salience gates endocannabinoid signaling at hypothalamic synapses (#101)
Parvocellular neuroendocrine cells (PNCs) in the paraventricular nucleus (PVN) of the hypothalamus form a critical node for coordination of the hypothalamic-pituitary-adrenal (HPA) axis. Neural circuits regulating PNC activity are finely tuned to distinguish valence of experience - both in terms of negative or positive affective quality, but also between novelty and predictability of stressful experiences. We tested the influence of such stressor state transitions on synaptic signaling by PNC-produced endocannabinoids (eCBs), known regulators of HPA adaptation. To assay eCB signaling in real-time, we obtained patch-clamp electrophysiological recordings from PNCs in slices prepared from naïve or stressed male rats (p21-35). Repeated exposure of juvenile male rats to homotypic stressors (ex. Immobilization or forced swim) resulted in progressive functional downregulation of presynaptic cannabinoid-1 receptor (CB1Rs) and loss of retrograde eCB signaling at PNC GABA synapses. Instead, exposure to a single, novel stress, following repeated homotypic stress, resulted in rapid recovery of eCB signaling. This recovery was mimicked by general recruitment of limbic circuits with electroconvulsive seizure (ECS) in vivo, and by in vitro manipulations that increase neural activity: elevated extracellular potassium or patterned synaptic stimulation. These findings together suggest that switches in eCB signaling capacity in PNCs reflects experience salience-dependent modulation of stress circuit activity.