Biology subjects

Ferreira, G.

Publications and source records attributed to Ferreira, G..

16 recordsLinked to original sources

bioRxiv2026

Endocannabinoid-dopamine interactions mediate incidental associations in the hippocampus

Reinforced conditioning allows individuals predicting future events with high confidence. However, many daily behaviours rely on unreinforced connections of neutral stimuli, called Incidental Associations (IAs), which enhance predictive capacity in unstable environments and are observed across species. IAs can be studied through sensory preconditioning paradigms, where two neutral stimuli (S1/S2) are presented together in a preconditioning phase, followed by classical conditioning of S1 with a potent reinforcer. As a result, subjects present a direct response to the S1 stimulus, but also display mediated responses to the S2 stimulus never explicitly reinforced, indicating IA formation during preconditioning. Our previous work demonstrated that type-1 cannabinoid receptors (CB1 receptors) in the hippocampus are essential for this IA formation. As dopamine signaling is also important for this process, we investigate the role of interactions between these dopamine-cannabinoid systems in IA memory formation in the hippocampus. Extending our previous work on odor-taste association, using light-sound association we showed that global CB1 receptor knock-out or specific hippocampal CB1 receptor deletion also blocked mediated responses to sound (S2) while direct response to light (S1) was unaltered. Focusing on dopamine, we then found hippocampal dopaminergic activity is enhanced during paired presentations of S1 and S2 and that blockade of dopamine D1 receptor during preconditioning S1-S2 associations abolished mediated response to S2. Interestingly, mice lacking CB1 receptors specifically in D1-receptor-expressing cells (D1-CB1-KO) failed to show mediated responses for either light-sound or odor-taste associations, identifying this CB1 receptor population as critical for IA formation. Enhanced activation of CB1 receptors, through either increase of endocannabinoids (using degradation enzyme inhibition) or exogenous stimulation by cannabis-derived Delta-9-tetrahydrocannabinol (THC), was able to promote the formation of IAs under insufficient conditions. The effect of endogenous CB1 activation, but not THC, was blocked in D1-CB1-KO mice indicating that IA-facilitation by endogenous and exogenous receptor activation rely on different mechanisms. Overall, these data uncover new mechanisms underlying unreinforced associative learning.

neuroscience↗

bioRxiv2026

A cellular midbrain mechanism for executing fast and reliable escape

Escape from threat is one of the most ancient and conserved sensorimotor transformations and must satisfy two competing demands. It must be fast and reliable, because failing to escape genuine threats risks death, yet also selective, because escaping indiscriminately costs energy and missed resources 1,2. Speed and reliability favour a system with a low threshold that responds to the slightest indication of danger, whereas selectivity demands a high threshold that filters out innocuous stimuli -- yet both must be achieved simultaneously. While previous work has identified mechanisms for implementing selectivity 3-6, it is not known how the mammalian brain achieves speed and reliability once genuine threats have been identified. Here we use whole-cell recordings from dorsal periaqueductal gray (dPAG) neurons in behaving mice to show that the escape circuit resolves this tension via high intrinsic excitability at the single cell level. We find that while the membrane potential of dPAG neurons does not reach action potential threshold during exploratory behaviour, they require only a small amount of current to fire. Threat stimuli cause a sparse increase in synaptic input rate that, because of the high excitability, produces a sustained depolarizing voltage step that drives spiking and escape behaviour. Individual dPAG neurons respond similarly on escape and non-escape trials --what determines escape is the fraction of the dPAG population that is recruited, a finding we confirm with single-unit recordings in freely moving mice. The membrane voltage step response is also invariant to threat type, in contrast to superior colliculus neurons where membrane potential dynamics reflect stimulus identity. These findings reveal a single neuron mechanism for fast and reliable escape, in which the high intrinsic excitability of dPAG neurons transforms sparse, threat-evoked synaptic input into a rapid and stereotyped voltage signal, converting diverse threat representations into a uniform escape command.

neuroscience↗

bioRxiv2026

Astrocytic morphology in the Medial Habenula: sex differences and modulatory factors

The medial habenula (MHb) is an epithalamic structure involved in aversive processing and emotional regulation, notable for its marked cellular heterogeneity and high astrocyte density. This cellular composition suggests that astrocytes may play an important role in MHb structure and plasticity, potentially contributing to the regulation of emotional states. The aim of this study is to characterize sex-dependent astrocytic morphology in the MHb and determine how it is modulated by peripheral alterations and direct central manipulations. A high-fat diet (HFD) was used as a model of metabolic stress, and systemic lipopolysaccharide (LPS) administration was used to induce a peripheral inflammatory challenge. At the central level, a chemogenetic approach using Gi-DREADDs under the GFAP promoter allowed selective modulation of astrocytic intracellular signalling independently of peripheral influences. Preliminary results indicate sex-dependent morphological differences in MHb astrocytes across all these experimental conditions, supporting the idea that MHb astrocytes are sensitive to both peripheral and central disturbances and may represent a key cellular substrate linking body-brain interactions with emotional regulation.

neuroscience↗

bioRxiv2025

A role for prefrontal dopamine signaling in control of goal-directed actions

Impairments in behavioral flexibility commonly found across psychiatric disorders have often been attributed to a dysfunction of the medial prefrontal cortex (mPFC), notably in relation with altered dopamine transmission. However, how dopamine transmission shapes neuronal activity in the mPFC to allow adapting to a changing situation remains largely elusive. Here, we show that dopamine dynamics in the mPFC encode the value of instrumental actions, in particular during reversal learning. Such signal shapes the activity of mPFC dopaminoceptive neurons during reversal learning through the recruitment of heteromers formed by dopamine D1 and D2 receptors with NMDA receptors. In accordance, blockade of either D1/NMDA or D2/NMDA heteromers in the mPFC selectively impairs reversal of outcome identities but not learning and expression of initial action-outcome associations. Our findings provide mechanistic evidence for a central role of dopamine in the mPFC to allow updating goal-directed actions.

neuroscience↗

bioRxiv2025

Tree species natural regeneration in a tidal white-water floodplain forest of the Amazon River estuary

The Amazon hosts the worlds most diverse floodplain forests, characterized by tree communities adapted to seasonal flooding. In the estuary, these forests are driven by both fluvial and tidal dynamics, yet remain poorly studied. We assessed natural regeneration in a tidal white-water floodplain forest within the Fazendinha Environmental Protection Area, eastern Amazonia (Brazil). Regenerating individuals (DSH [≤] 5 cm) were sampled in 21 systematically distributed plots, classified into height classes, and analyzed with diversity indices, regeneration parameters, and ordination methods. We recorded 758 individuals from 43 taxa, 35 genera, and 20 families. Fabaceae was the richest and most abundant family, largely due to the oligarch Mora paraensis, which comprised >70% of individuals. Despite this dominance, Shannon diversity was high (H = 5.31), with 53.5% of species occurring as singletons or doubletons. Regeneration density reached 14,438 ind. ha{square}1, concentrated in the smallest classes, with few species spanning all classes. Subtle compositional shifts occurred with river distance, though dominants remained broadly distributed. Our findings highlight the resilience of oligarchic species and the vulnerability of rare taxa, advancing knowledge of estuarine floodplain ecology and providing essential baseline information for conservation and management in this understudied region.

ecology↗

bioRxiv2025

Obesogenic Diet Impairs Social Memory Through Alterations of Hippocampal CA2 Excitability and Oxytocin Signaling

While obesity induces cardio-metabolic disorders and cognitive deficits, the underlying neural mechanisms remain unexplored. In mice, exposure to an obesogenic high-fat and sugar diet (HFD) resulted in social recognition memory deficits in both males and females, a process that is dependent upon hippocampal area CA2 and oxytocin signaling. HFD-fed mice had stronger inputs onto CA2 pyramidal neurons that led to increased action potential firing, without altering intrinsic properties or inhibitory transmission. Chemogenetic CA2 pyramidal neuron inhibition in HFD-fed mice rescued social novelty discrimination, with novelty preference in males and familiarity preference in females. We also observed that HFD in both males and females impaired the ability of oxytocin receptor activation to be permissive for endocannabinoid-mediated plasticity. Furthermore, chemogenetic inhibition of CA2 pyramidal neurons rescued oxytocin-induced endocannabinoid plasticity in both HFD-fed male and female mice, whereas it prevented endocannabinoid plasticity in control diet-fed mice. In a concentration-dependent manner, oxytocin restored potentiation of excitatory responses, allowed for endocannabinoid plasticity at CA2 inhibitory synapses, and rescued social novelty discrimination in HFD-fed mice. This study uncovers mechanisms linking neuromodulation and endocannabinoid-mediated plasticity in social memory processes and reveals the deleterious consequences of an obesogenic diet on this process.

neuroscience↗

bioRxiv2025

Developmental vitamin A deficiency induces sex-specific reward processing alterations through a dysregulation of the mesolimbic dopamine transmission in mice

Neurodevelopmental psychiatric diseases such as schizophrenia or affective disorders share common symptomatic dimensions, in particular reward processing dysfunctions, associated with dysregulation of dopamine (DA) transmission. Retinoic acid (RA) homeostasis is altered across psychiatric disorders but whether impaired developmental RA signaling impacts the functionality of DA-related reward processing at adulthood remains poorly explored. Herein, we explored in male and female mice how developmental vitamin A deficiency (VAD), as a model of blunted RA signaling, could impact motivational processes through a modulation of mesolimbic DA transmission. Behavioral performances were evaluated using operant conditioning tasks, parallel with investigations of the integrity of DA transmission through biochemical analyses of markers of DA transmission and measures of DA dynamics using DA biosensor coupled with fiber photometry. Finally, chemogenetic manipulation of the mesolimbic DA pathway was used to normalize DA transmission and assess the effect on motivational performance in VAD offspring. Developmental VAD induced sex-specific alterations of reward-related processes at adulthood. Indeed, while female behavioral performances were spared, VAD males exhibited elevated instrumental performance and impulsivity. These behavioral alterations were coherent with reduced DA transporter (DAT) expression and increased DA dynamic in the mesolimbic pathway. Strikingly, chemogenetic inhibition of the mesolimbic DA pathway normalized motivational performance in VAD males. Our results show that developmental RA hyposignaling induces sex-specific reward processing alterations in adulthood through hyperactivity of the mesolimbic DA pathway. Our data support that developmental impairment in RA signaling might be at the core of reward-related symptoms across psychiatric disorders.

neuroscience↗

bioRxiv2025

The malate aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes

Brown adipose tissue (BAT) plays a central role in thermogenesis by coupling fatty acid oxidation to heat production. Efficient BAT thermogenic activity requires enhanced glycolytic flux, which in turn depends on continuous regeneration of cytosolic NAD to sustain glyceraldehyde-3-phosphate dehydrogenase activity. This regeneration is mediated by three main pathways: lactate dehydrogenase, the glycerol-3-phosphate shuttle, and the malate-aspartate shuttle (MASh). We previously showed that inhibition of the mitochondrial pyruvate carrier increases energy expenditure in brown adipocytes via MASh activation. However, the specific contribution of MASh to BAT energy metabolism remains poorly defined. Here, we show that MASh is functional and directly regulates lipid metabolism in BAT. Enzymatic activities of cytosolic and mitochondrial malate dehydrogenases and glutamic-oxaloacetic transaminases in BAT were comparable to those in the liver. Using a reconstituted system of isolated BAT mitochondria and cytosolic MASh enzymes, we demonstrated that extra-mitochondrial NADH is efficiently reoxidized in a glutamate-dependent manner via MASh. Genetic silencing of the mitochondrial carriers critical to MASh--namely the oxoglutarate carrier (OGC1) and aspartate-glutamate carrier (Aralar1) had no apparent effects on respiratory rates. However, silencing either OGC1 or Aralar1 led to the accumulation of small lipid droplets and impaired norepinephrine-induced lipolysis. Taken together, our data indicate a novel role of MASh in regulating BAT lipid homeostasis with potential implications to body energy expenditure and thermogenesis.

biochemistry↗

bioRxiv2025

Obesogenic diet impairs memory consolidation via the hippocampal endocannabinoid system

Although obesogenic high-fat/high-sugar diets impair memory function in humans and rodents, the underlying mechanisms remain elusive. Given that the brain endocannabinoid system and type-1 cannabinoid receptors (CB1R) control memory processes and are overactive under obesogenic conditions, we studied whether the effects of obesogenic diet consumption on memory function are dependent on this system. Using an object recognition memory (ORM) task in male mice, we showed that CB1R activity is required for obesogenic diet-induced impairment of long-term memory performance. This impairment was prevented by post-training systemic blockade of CB1R, which also normalized training-induced hippocampal cellular and synaptic overactivation. Consistently, obesogenic diet potentiated the increase of hippocampal endocannabinoid levels and enhanced CB1R expression induced by ORM, and genetic CB1R deletion from hippocampal glutamatergic neurons abolished diet-induced memory deficits. Strikingly, obesogenic diet enhanced the hippocampal mTOR pathway in a CB1R-dependent manner, and pharmacological mTOR inhibition after training rescued diet-induced ORM consolidation deficits. Together, these results establish how an obesogenic environment can lead to hippocampal overactivation of the endocannabinoid system and of the mTOR pathway to eventually impair memory consolidation. Thus, these results shed light on the mechanisms of diet-induced cognitive alterations and may pave the way to novel therapeutic strategies. HighlightsO_LIObesogenic diet induces long-term memory deficits, which are rescued by CB1R blockade C_LIO_LICB1R blockade rescues diet-induced aberrant hippocampal activity/plasticity after training C_LIO_LIObesogenic diet enhances hippocampal endocannabinoid levels and CB1R after training C_LIO_LIDeletion of hippocampal CB1R rescues diet-induced long-term memory deficits C_LIO_LIObesogenic diet enhances hippocampal mTOR phosphorylation after training C_LIO_LImTOR inhibition rescues diet-induced memory consolidation deficits C_LI

neuroscience↗

bioRxiv2025

Feeding-fasting cycle of obesogenic food determines glucocorticoid neuromodulation of cortico-hippocampal activities sustaining long-term memory

BackgroundHighly caloric food consumed around the clock perturbs the metabolism and cognitive functioning. We hypothesized that obesogenic food could alter neuronal representations of memory depending on the feeding-fasting cycle. MethodsWe tracked memory performance, dendritic spine dynamics and neuronal representations of memory in C57Bl6J mice fed obesogenic food ad libitum from peri-adolescence. We aimed to correct energy rich diet-induced plasticity deficits and cognitive impairment with time-restricted feeding in males and females. We further used chemogenetics, pharmacology and knock-in mice to investigate functional correlates underlying diet-induced neurocognitive impairments. ResultsWe find that changes in the feeding-fasting cycle reverted the effects of ad libitum obesogenic food on memory impairment in both sexes (n=55, p=0.003). Concurrently, it also corrected the increased dendritic spine maintenance and neuroactivity in hippocampus and the decreased spine maintenance and activity in parietal cortex (n=48, p<0.005). Bi-directional effects in cortex and hippocampus mediated by glucocorticoid signalling are causal to behavioural changes (n=91, p=0.0008), and scaling hippocampal with cortical activities restored memory in mice fed obesogenic food (n=44, p=0.02). ConclusionThese results indicate that meal scheduling is a promising approach to confront glucocorticoid signalling bias and memory deficits caused by obesogenic food. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWhat and when we eat contributes to our health. This is particularly worrisome for kids and adolescents because of the lifelong effects that unrestricted snacking on highly caloric food could cause on brain maturation. A variety of school policies and nutritional programs have emerged to prevent poor nutritional habits. But obesity is on the rise and a major cause of neurological disabilities difficult to detect and treat. Human studies are limited by the size and duration of sampling with low resolution metrics to prove causality between nutritional habits and cognitive health trajectory. Animal studies showed that all-day snacking on highly caloric food disrupts innate biological rhythms that influence hormonal secretions, neuronal structure and function in brain regions that encode, store and retrieve memories. It isnt known if, like adipocytes and hepatocytes, the brain in obesity can develop glucocorticoid resistance -a state that would prevent the robust but complex effects of this hormone on memory- to the point that researchers still question whether glucocorticoids are a cause or solution to obesity related-brain comorbidities. Added value of this studyLongitudinal sampling of several metrics at multiple timepoints in mice fed highly caloric food since peri-adolescence up to adulthood showed that the trajectory of obesity-related brain comorbidities is corrected when reinstating the feeding/fasting cycle, albeit consuming highly caloric food. Glucocorticoid resistance -manifesting as receptor phosphorylation deficits impeding coincidence detection between glucocorticoid and neuronal activities -was reversible when reinstating the feeding/fasting cycle, albeit consuming highly caloric food. Studies in receptor mutant mice lacking a phosphorylation site-independent of glucocorticoids showed it is required to reinstate neuroplasticity to changes of feeding/fasting cycle, albeit consuming highly caloric food. Fos-trapping experiments showed less engagement of pyramidal neurons in the cortex when activity-dependent phosphorylation of glucocorticoid receptor was low, and more in the hippocampus of mice fed obesogenic diet, which reinstating the feeding/fasting cycle reverted, albeit consuming highly caloric food. Finally, chemogenetic experiments confirmed the requirement for the co-engagement of cortical and hippocampal pyramidal neurons to fully remember, despite poor nutritional habits. Implications of all the available evidenceThe cortico-hippocampal activities necessary for remembering are uncoupled by obesogenic food consumed ad libitum but not on meal scheduling, extending neuroimaging correlation studies in obese adolescents. Poor nutritional habits cause glucocorticoid resistance in the brain as previously suggested, with altered neuronal representation of memory that meal scheduling corrected. This result should transform school policies and familial nutritional habits to promote cognitive health. Future research will develop allosteric ligands targeting phosphorylation motifs in the glucocorticoid receptor as more specific alternative to orthosteric ligands for the treatment of obesity-related brain comorbidities.

neuroscience↗

bioRxiv2024

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

The consumption of calorie-rich diet has adverse effects on short and long-term memory, especially when introduced early in life when the brain is still maturing. Time-restricted feeding (TRF) without calorie restriction has proven to be an efficient strategy to reduce the deleterious effects of diet-induced obesity on metabolism. TRF was also shown to be beneficial to restore long-term memory in Alzheimer rodent models. Here, we provide evidence that four weeks of TRF restore the rhythmicity of some metabolic parameters together with short and long-term memory in mice fed a high fat-high sucrose (HFS) diet since weaning. Hippocampal translatome analyses indicated that impaired memory of mice under ad libitum HFS diet is accompanied by changes in genes associated with thyroid hormone signaling and astrocytic genes involved in the regulation of glutamate neurotransmission. TRF restored the diurnal expression variation of part of these genes and intra-hippocampal infusion of T3, the active form of thyroid hormone, rescued the memory performances of ad libitum HFS diet-fed mice. Thus, TRF demonstrates positive effects on both metabolism and memory in mice fed an obesogenic diet, highlighting this nutritional approach as a powerful tool in addressing obesity and its related comorbidities in mice. The analogous time-restricted eating in humans is an easy to implement lifestyle intervention that should now be tested in obese adolescents with memory alterations.

neuroscience↗

bioRxiv2023

Identification of a binding site for bupropion in Gloeobacter violaceus ligand-gated ion channel

Bupropion is an atypical antidepressant and smoking cessation drug which causes adverse effects such as insomnia, irritability, and anxiety. Bupropion inhibits dopamine and norepinephrine reuptake transporters and eukaryotic cation-conducting pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine (nACh) and serotonin type 3A (5-HT3A) receptors, at clinically relevant concentrations. However, the binding sites and binding mechanisms of bupropion are still elusive. To further understand the inhibition of pLGICs by bupropion, in this work, using a prokaryotic homologue of pLGICs as a model, we examined the inhibitory potency of bupropion in Gloeobacter violaceus ligand-gated ion channel (GLIC), a proton-gated ion channel. Bupropion inhibited proton-induced currents in GLIC with an inhibitory potency of 14.9 {+/-} 2.0 M, comparable to clinically attainable concentrations previously shown to also modulate eukaryotic pLGICs. Using single amino acid substitutions in GLIC and two-electrode voltage-clamp recordings, we further determined a binding site for bupropion in the lower third of the first transmembrane segment M1 at residue T214. The sidechain of M1 T214 together with additional residues of M1 and also of M3 of the adjacent subunit have previously been shown to contribute to binding of other lipophilic molecules like allopregnanolone and pregnanolone. SIGNIFICANCEGLIC, Gloeobacter ligand-gated ion channel, has been extensively used as a model to identify and understand binding sites and mechanisms for cholesterol, neurosteroids, and anesthetics interacting with neurotransmitter-gated ion channels, such as, GABAA receptors and nicotinic acetylcholine receptors. Recently, increasing evidence has revealed that another neurotransmitter-gated ion channel, the serotonin type 3A receptor, binds to an atypical antidepressant, bupropion, at clinically relevant concentrations. Our work here proposes a binding site for bupropion in GLIC and suggests a new approach to characterize binding mechanisms of bupropion in other neurotransmitter-gated ion channels.

neuroscience↗

bioRxiv2022

Obesogenic diet induces circuit-specific memory deficits in mice

Obesity is associated with neurocognitive dysfunction, including memory deficits. This is particularly worrisome during adolescence, which represents a crucial period for maturation of brain structures, such as the hippocampus which are crucial for cognition. In rodent models, we recently reported that memory impairments induced by obesogenic high-fat diet (HFD) intake during the periadolescent period can be reversed by chemogenetic manipulation of the ventral hippocampus (vHPC). Here, we used an intersectional viral approach in HFD-fed male mice to chemogenetically inactivate specific vHPC efferent pathways to nucleus accumbens or medial prefrontal cortex during memory tasks. We first demonstrated that HFD enhanced activation of both pathways after training and that our chemogenetic approach was effective in normalising this activation. Inactivation of the vHPC-nucleus accumbens pathway rescued HFD-induced deficits in recognition but not location memory. Conversely, inactivation of the vHPC-medial prefrontal cortex pathway restored location but not recognition memory impairments produced by HFD. Either pathway manipulation did not affect exploration, locomotion or anxiety-like behaviour. These findings suggest that HFD intake throughout adolescence impairs different types of memory through overactivation of specific hippocampal efferent pathways and that targeting these overactive pathways has therapeutic potential.

neuroscience↗

bioRxiv2022

The ventral striatum contributes to energy balance

Accumulating evidence points to dysregulations of common brain systems in eating disorders (ED), the Nucleus Accumbens (NAc) in particular. However, to which extent alterations in NAc activity contribute to ED-like dimensions remains unclear. Using chemogenetic manipulations of dopamine D1 receptor-expressing and D2-expressing neuronal subpopulations of the NAc in male mice, we assessed their respective roles in incentive processes, food intake and the balance between feeding and exercise-mediated energy expenditure. We found that D1-neurons facilitate effort for a food reward but decreased food intake, while D2-neurons have opposite effects. The anorexigenic influence of D1-neurons was accompanied by increased voluntary exercise while the orexigenic effect of D2-neurons was concomitant with decreased running, congruent with D2-neurons being more active than D1-neurons during feeding while it is the opposite during running. Chronic manipulations of each subpopulations had limited effects on energy balance. However, repeated activation of D1-neurons combined with inhibition of D2-neurons biased behavior toward activity-related energy expenditure leading to weight/fat loss, whilst the opposite manipulations favored energy intake and hence weight/fat gain. Strikingly, concomitant activation of D1-neurons and inhibition of D2-neurons precipitated weight loss in anorexia models. These results suggest that dysregulations of NAc dopaminoceptive neurons might be at the core of EDs.

neuroscience↗

bioRxiv2022

Heme overdrive rewires pan-cancer cell metabolism

Porphyrin overdrive rewires pan-cancer cell metabolismAll cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways for their oncogenic growth. We coined this essential metabolic rewiring porphyrin overdrive and determined that it is cancer-universal, cancer-essential, and cancer-specific. While porphyrin overdrive is absent in differentiated cells or somatic stem cells, it is present in patient-derived tumor progenitor cells, demonstrated by single cell RNAseq, and in early embryogenesis. Among the major drivers are proteins involved in biosynthesis of heme intermediates and heme trafficking. CRISPR/Cas9 editing to engineer leukemia cells with impaired heme biosynthetic steps confirmed our whole genomic data analyses that porphyrin overdrive is linked to oncogenic states and cellular differentiation. In conclusion, we identified a dependence of cancer cells on non-homeostatic heme metabolism, and we targeted this cancer metabolic vulnerability with a novel "bait-and-kill" strategy to eradicate malignant cells. One-Sentence SummaryPorphyrin overdrive reprograms cancer cellular metabolism.

cancer biology↗

bioRxiv2020

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

1In 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.

neuroscience↗