Induction of Anxiety-Like Phenotypes by Knockdown of Cannabinoid Type-1 Receptors in the Amygdala of Marmosets

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases.Here,we investigated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.

Developmental Exposure to Bisphenol A Degrades Auditory Cortical Processing in Rats

Developmental exposure to bisphenol A(BPA),an endocrine-disrupting contaminant,impairs cognitive function in both animals and humans.However,whether BPA affects the development of primary sensory systems,which are the first to mature in the cortex,remains largely unclear.Using the rat as a model,we aimed to record the physiological and structural changes in the primary auditory cortex(A1)following lactational BPA exposure and their possible effects on behavioral outcomes.We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test.A significant alteration in spectral and temporal processing was also recorded in their A1,manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons.These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1.Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination,particularly in the temporal domain.Thus,the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.