title: Morphological and behavioral evidence for impaired prefrontal cortical function in female CB1 receptor deficient mice.
abstract: The medial prefrontal cortex (mPFC) is known to regulate higher order processes like cognitive flexibility. Accumulating behavioral evidence suggests that endocannabinoid (eCB) signaling regulates neuronal architecture within the PFC, as well as certain forms of cognitive flexibility; however, all of these studies have been performed in male rodents and it is currently unknown whether the eCB system performs a similar role in females. To this extent, dendritic morphology of layer II/III neurons in the infra- and prelimbic regions of the mPFC was analyzed and cognitive ability and flexibility in a fixed-platform Morris water maze task was assessed in adult female CB1 receptor knockout (CB1KO) mice. Similar to data generated in male mice, female mice exhibited no difference in acquisition relative to wildtype (WT); however, during reversal learning, CB1KO females spent more time in the original training quadrant and took significantly longer to learn the location of the new platform relative to WT. Within the mPFC, female mice had reduced length and complexity of layer II/III neurons within the prelimbic, but not infralimbic region of the PFC. Taken together, these findings indicate that the role of eCB signaling in cognitive flexibility is independent of sex and disrupted CB1 receptor signaling results in compromised structure and function of the PFC, at least within the prelimbic division.
authors.affiliation: University of British Columbia, Department of Psychology, 2136 West Mall, Vancouver, Canada V6T 1Z4. Electronic address: ttylee@gmail.com.
authors.forename: Tiffany T-Y
authors.initials: TT
authors.lastname: Lee
authors.affiliation: Laboratory of Neuroendocrinology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Filipski
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Hill
authors.affiliation: Laboratory of Neuroendocrinology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003071:Cognition; D005260:Female; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology*; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency* / Q000378:metabolism*; D012193:Reversal Learning; D012737:Sex Factors; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D043884:Receptor, Cannabinoid, CB1
keywords: CB1 receptor knockout; Cognitive flexibility; Endocannabinoid; Prefrontal cortex; Prelimbic; Sex difference