Experience salience gates endocannabinoid signaling at hypothalamic synapses.
Alterations in synaptic endocannabinoid signaling are a widespread neurobiological consequence of many in vivo experiences, including stress. Here, we report that stressor salience is critical for bidirectionally modifying presynaptic CB-1 receptor (CB1R) function at hypothalamic GABA synapses controlling the neuroendocrine stress axis in male rats. While repetitive, predictable stressor exposure impairs presynaptic CB1R function, these changes are rapidly reversed upon exposure to a high salience experience such as novel stress or by manipulations that enhance neural activity levels in vivo or in vitro. Together these data demonstrate that experience salience, through alterations in afferent synaptic activity, induces rapid changes in endocannabinoid signaling.
Hotchkiss Brain Institute, Department of Physiology and Pharmacology, Department of Psychology, and Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
Jaclyn I
JI
Wamsteeker Cusulin
Laura
L
Senst
G Campbell
GC
Teskey
Jaideep S
JS
Bains
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D063388:Endocannabinoids / Q000378:metabolism*; D007031:Hypothalamus / Q000473:pathology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009812:Odorants; D010880:Piperidines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000209:etiology / Q000473:pathology*; D013550:Swimming / Q000523:psychology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D048588:Benzoxazines; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D011189:Potassium Chloride
GABA; endocannabinoids; glucocorticoids; novelty; stress; synapse