Chemogenetic silencing of hippocampus and amygdala reveals a double dissociation in periadolescent obesogenic diet-induced memory alterations

Abstract

1ABSTRACTIn addition to numerous metabolic comorbidities, obesity is associated with several adverse neurobiological outcomes, especially learning and memory alterations. Obesity prevalence is rising dramatically in youth and is persisting in adulthood. This is especially worrying since adolescence is a crucial period for the maturation of certain brain regions playing a central role in memory processes such as the hippocampus and the amygdala. We previously showed that periadolescent exposure to obesogenic high-fat diet (HFD) had opposite effects on hippocampus- and amygdala-dependent memory, impairing the former and enhancing the latter. However, the causal role of these two brain regions in periadolescent HFD-induced memory alterations remains unclear. Here, we first showed that periadolescent HFD induced long-term, but not short-term, object recognition memory deficits, specifically when rats were exposed to a novel context. Using chemogenetic approaches to inhibit targeted brain regions, we then demonstrated that recognition memory deficits are dependent on the activity of the ventral hippocampus, but not the basolateral amygdala. On the contrary, the HFD-induced enhancement of conditioned odor aversion requires specifically amygdala activity. Taken together, these findings suggest that HFD consumption throughout adolescence impairs long-term object recognition memory through the overactivation of the ventral hippocampus during memory acquisition. Moreover, these results further highlight the bidirectional effects of adolescent HFD on hippocampal and amygdala functions.

Bidirectional modulation of hippocampal and amygdala synaptic plasticity by post‐weaning obesogenic diet intake in male rats: Influence of the duration of diet exposure

“…Our previous results show that 2-3 months of HFD intake, corresponding to the periadolescent period, has opposite effects on hippocampal and amygdala-dependent memory, impairing hippocampal-dependent spatial and relational memory (Boitard et al, 2012(Boitard et al, , 2014(Boitard et al, , 2016 but enhancing amygdala-dependent emotional memory (Boitard et al, 2015(Boitard et al, , 2016Naneix et al, 2020). Our BLA plasticity data fits with the emotional memory effect suggesting this could represent a cellular basis of the behavioural effect as we previously suggested (Boitard et al, 2015).…”

“…During adolescence, the maturation of brain structures such as the hippocampus and the amygdala is crucial for cognitive and emotional functions (Andersen, 2003;Spear, 2000). We and others recently demonstrated that adolescent obesity, induced by post-weaning high-fat diet (HFD) consumption, impaired hippocampal-dependent spatial and relational memories in animal models (Boitard et al, 2012(Boitard et al, , 2014Khazen, Abu Hatoum, Ferreira, & Maroun, 2019;Valladolid-Acebes et al, 2013) whereas the same HFD exposure enhanced amygdala-dependent emotional memory (Boitard et al, 2015(Boitard et al, , 2016Naneix et al, 2020). This bidirectional effect of post-weaning HFD intake on hippocampal-and amygdala-dependent memory suggests cellular changes at the level of the hippocampus and the amygdala Mouna Maroun and Guillaume Ferreira contributed equally to this work.…”

Time-restricted feeding prevents memory impairments induced by obesogenic diet consumption in mice, in part through hippocampal thyroid hormone signaling

“…Importantly, we found that HFS diet impaired hippocampal-dependent memories when started in juveniles, but did not affect memory when started at adulthood [8], through aberrant ac6vity of the hippocampus [10,11]. Specifically, such memory impairments have been found to be associated with higher c-fos expression in the hippocampus and hippocampal efferent pathways to striatal and prefrontal areas [10,11] as well as aberrant synap6c transmission and plas6city in CA1 [12]. Interes6ngly, chemogene6c manipula6on of the hippocampus or its efferent pathways rescued memory deficits for object loca6on and long-term object recogni6on [11,13].…”

“…Our group has developed a model of juvenile HFS consump6on in rodents, from weaning to adulthood and showed that this paradigm induced memory deficits [8,9]. Importantly, we found that HFS diet impaired hippocampal-dependent memories when started in juveniles, but did not affect memory when started at adulthood [8], through aberrant ac6vity of the hippocampus [10,11]. Specifically, such memory impairments have been found to be associated with higher c-fos expression in the hippocampus and hippocampal efferent pathways to striatal and prefrontal areas [10,11] as well as aberrant synap6c transmission and plas6city in CA1 [12].…”

“…Specifically, such memory impairments have been found to be associated with higher c-fos expression in the hippocampus and hippocampal efferent pathways to striatal and prefrontal areas [10,11] as well as aberrant synap6c transmission and plas6city in CA1 [12]. Interes6ngly, chemogene6c manipula6on of the hippocampus or its efferent pathways rescued memory deficits for object loca6on and long-term object recogni6on [11,13]. However, the molecular mechanism underpinnings of the HFS diet-induced memory impairments have not been iden6fied yet.…”