title: Cannabinoid transmission in the basolateral amygdala modulates fear memory formation via functional inputs to the prelimbic cortex.
abstract: The cannabinoid CB1 receptor system is critically involved in the control of associative fear memory formation within the amygdala-prefrontal cortical pathway. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the prelimbic division (PLC) of the medial prefrontal cortex (mPFC). However, the precise role of CB1 receptor transmission within the BLA during the processing of fear memory is not fully understood. We examined the potential role of BLA CB1 receptor transmission during an olfactory fear-conditioning procedure in rats by pharmacologically modulating CB1 cannabinoid transmission directly within the BLA. We report that blockade of BLA CB1 receptor transmission prevents the acquisition of associative fear memory, while having no effect on the recall or consolidation of these memories. In contrast, intra-BLA activation of CB1 receptor transmission or blockade of endocannabinoid reuptake strongly potentiated the emotional salience of normally subthreshold fear-conditioning stimuli. In addition, pharmacological inactivation of the mPFC before intra-BLA CB1 activation blocked CB1-receptor-mediated potentiation of fear memory formation. In vivo single-unit electrophysiological recordings within the PLC revealed that modulation of BLA CB1 receptor transmission strongly influences neuronal activity within subpopulations of PLC neurons, with blockade of intra-BLA CB1 receptor transmission inhibiting spontaneous PLC neuronal activity and activation of CB1 receptors producing robust activation, in terms of neuronal firing frequency and bursting activity. Thus, cannabinoid transmission within the BLA strongly modulates the processing of associative fear memory via functional interactions with PLC neuronal populations.
authors.affiliation: Department of Anatomy and Cell Biology, The Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Huibing
authors.initials: H
authors.lastname: Tan
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Lauzon
authors.forename: Stephanie F
authors.initials: SF
authors.lastname: Bishop
authors.forename: Ning
authors.initials: N
authors.lastname: Chi
authors.forename: Melanie
authors.initials: M
authors.lastname: Bechard
authors.forename: Steven R
authors.initials: SR
authors.lastname: Laviolette
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000344:Afferent Pathways / Q000502:physiology; D000679:Amygdala / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D005239:Fear / Q000502:physiology*; D007839:Functional Laterality; D008297:Male; D008568:Memory / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D012903:Smell / Q000187:drug effects / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; 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; C107594:N-(4-hydroxyphenyl)arachidonylamide