Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation.

The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role in memory. While previous studies have primarily associated the HPC with food intake inhibition, recent research suggests a role in appetitive processes. Here we identified spatially distinct neuronal populations within the dorsal HPC (dHPC) that respond to either fats or sugars, potent natural reinforcers that contribute to obesity development.

Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake.

Oxytocin (OT) is a neuropeptide produced in the paraventricular (PVH) and supraoptic (SON) nuclei of the hypothalamus. Either peripheral or central administration of OT suppresses food intake through reductions in meal size. However, pharmacological approaches do not differentiate whether observed effects are mediated by OT neurons located in the PVH or in the SON.

Hippocampus Oxytocin Signaling Promotes Prosocial Eating in Rats.

Background: Oxytocin (OT) is a hypothalamic neuropeptide involved in diverse physiological and behavioral functions, including social-based behavior and food intake control. The extent to which OT's role in regulating these 2 fundamental behaviors is interconnected is unknown, which is a critical gap in knowledge given that social factors have a strong influence on eating behavior in mammals. Here, we focus on OT signaling in the dorsal hippocampus (HPCd), a brain region recently linked to eating and social memory, as a candidate system where these functions overlap.

Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling.

Western diet (WD) consumption during early life developmental periods is associated with impaired memory function, particularly for hippocampus (HPC)-dependent processes. We developed an early life WD rodent model associated with long-lasting HPC dysfunction to investigate the neurobiological mechanisms mediating these effects. Rats received either a cafeteria-style WD (ad libitum access to various high-fat/high-sugar foods; CAF) or standard healthy chow (CTL) during the juvenile and adolescent stages (postnatal days 26-56).

Ventral hippocampus neurons encode meal-related memory.

The ability to encode and retrieve meal-related information is critical to efficiently guide energy acquisition and consumption, yet the underlying neural processes remain elusive. Here we reveal that ventral hippocampus (HPCv) neuronal activity dynamically elevates during meal consumption and this response is highly predictive of subsequent performance in a foraging-related spatial memory task. Targeted recombination-mediated ablation of HPCv meal-responsive neurons impairs foraging-related spatial memory without influencing food motivation, anxiety-like behavior, or escape-mediated spatial memory.

Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation.

The hippocampus (HPC), traditionally known for its role in learning and memory, has emerged as a controller of food intake. While prior studies primarily associated the HPC with food intake inhibition, recent research suggests a critical role in appetitive processes. We hypothesized that orexigenic HPC neurons differentially respond to fats and/or sugars, potent natural reinforcers that contribute to obesity development.

Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling.

Western diet (WD) consumption during development yields long-lasting memory impairments, yet the underlying neurobiological mechanisms remain elusive. Here we developed an early life WD rodent model to evaluate whether dysregulated hippocampus (HPC) acetylcholine (ACh) signaling, a pathology associated with memory impairment in human dementia, is causally-related to WD-induced cognitive impairment. Rats received a cafeteria-style WD (access to various high-fat/high-sugar foods; CAF) or healthy chow (CTL) during the juvenile and adolescent periods (postnatal days 26-56).

Amylin Modulates a Ventral Tegmental Area-to-Medial Prefrontal Cortex Circuit to Suppress Food Intake and Impulsive Food-Directed Behavior.

Background: A better understanding of the neural mechanisms regulating impaired satiety to palatable foods is essential to treat hyperphagia linked with obesity. The satiation hormone amylin signals centrally at multiple nuclei including the ventral tegmental area (VTA). VTA-to-medial prefrontal cortex (mPFC) projections encode food reward information to influence behaviors including impulsivity.

Hypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats.

The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes in male rats. Specifically, results reveal that MCH neuron Ca activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses.

The gut-brain axis and cognitive control: A role for the vagus nerve.

Survival requires the integration of external information and interoceptive cues to effectively guide advantageous behaviors, particularly foraging and other behaviors that promote energy acquisition and consumption. The vagus nerve acts as a critical relay between the abdominal viscera and the brain to convey metabolic signals. This review synthesizes recent findings from rodent models and humans revealing the impact of vagus nerve signaling from the gut on the control of higher-order neurocognitive domains, including anxiety, depression, reward motivation, and learning and memory.

Early Life Low-Calorie Sweetener Consumption Impacts Energy Balance during Adulthood.

Children frequently consume beverages that are either sweetened with sugars (sugar-sweetened beverages; SSB) or low-calorie sweeteners (LCS). Here, we evaluated the effects of habitual early life consumption of either SSB or LCS on energy balance later during adulthood. Male and female rats were provided with chow, water, and a solution containing either SSB (sucrose), LCS (acesulfame potassium (ACE-K) or stevia), or control (no solution) during the juvenile and adolescent periods (postnatal days 26-70).

Ventral hippocampus-lateral septum circuitry promotes foraging-related memory.

Remembering the location of a food or water source is essential for survival. Here, we reveal that spatial memory for food location is reflected in ventral hippocampus (HPCv) neuron activity and is impaired by HPCv lesion. HPCv mediation of foraging-related memory involves communication to the lateral septum (LS), as either reversible or chronic disconnection of HPCv-to-LS signaling impairs spatial memory retention for food or water location.

Mitochondrial DNA variation in Alzheimer's disease reveals a unique microprotein called SHMOOSE.

Mitochondrial DNA variants have previously associated with disease, but the underlying mechanisms have been largely elusive. Here, we report that mitochondrial SNP rs2853499 associated with Alzheimer's disease (AD), neuroimaging, and transcriptomics. We mapped rs2853499 to a novel mitochondrial small open reading frame called SHMOOSE with microprotein encoding potential.

Longitudinal Evidence of a Vicious Cycle Between Nucleus Accumbens Microstructure and Childhood Weight Gain.

Purpose: Pediatric obesity is a growing public health concern. Previous work has observed diet to impact nucleus accumbens (NAcc) inflammation in rodents, measured by the reactive proliferation of glial cells. Recent work in humans has demonstrated a relationship between NAcc cell density-a proxy for neuroinflammation-and weight gain in youth; however, the directionality of this relationship in the developing brain and association with diet remains unknown.

Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats.

Mutations in the putative glutamatergic synapse scaffolding protein SAP97 are associated with the development of schizophrenia in humans. However, the role of SAP97 in synaptic regulation is unclear. Here we show that SAP97 is expressed in the dendrites of granule neurons in the dentate gyrus but not in the dendrites of other hippocampal neurons.

The menace of obesity to depression and anxiety prevalence.

The incidence of depression and anxiety is amplified by obesity. Mounting evidence reveals that the psychiatric consequences of obesity stem from poor diet, inactivity, and visceral adipose accumulation. Resulting metabolic and vascular dysfunction, including inflammation, insulin and leptin resistance, and hypertension, have emerged as key risks to depression and anxiety development.

Prolonged saturated, but not monounsaturated, high-fat feeding provokes anxiodepressive-like behaviors in female mice despite similar metabolic consequences.

Obesity significantly increases the risk for anxiety and depression. Our group has recently demonstrated a role for nucleus accumbens (NAc) pro-inflammatory nuclear factor kappa-B (NFkB) signaling in the development of anxiodepressive-like behaviors by diet-induced obesity in male mice. The NAc is a brain region involved in goal-oriented behavior and mood regulation whose functions are critical to hedonic feeding and motivation.

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward.

Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning.

Western Diet Consumption During Development: Setting the Stage for Neurocognitive Dysfunction.

The dietary pattern in industrialized countries has changed substantially over the past century due to technological advances in agriculture, food processing, storage, marketing, and distribution practices. The availability of highly palatable, calorically dense foods that are shelf-stable has facilitated a food environment where overconsumption of foods that have a high percentage of calories derived from fat (particularly saturated fat) and sugar is extremely common in modern Westernized societies. In addition to being a predictor of obesity and metabolic dysfunction, consumption of a Western diet (WD) is related to poorer cognitive performance across the lifespan.

Energy Compensation Following a Supervised Exercise Intervention in Women Living With Overweight/Obesity Is Accompanied by an Early and Sustained Decrease in Non-structured Physical Activity.

Background/objectives: Body composition (BC) does not always vary as a function of exercise induced energy expenditure (exercise EE - resting EE). Energy balance variables were measured to understand energy compensation (EC) in response to an exercise intervention performed at low (LOW) or moderate (MOD) intensity.

Subjects/methods: Twenty-one women with overweight/obesity (33 ± 5 kg/m; 29 ± 10 yrs; 31 ± 4 ml O/kg/min) were randomized to a 3-month LOW or MOD (40 or 60% of VȮ, respectively) matched to expend 1500 kcal/week (compliance = 97 ± 5%).

GLP-1/dexamethasone inhibits food reward without inducing mood and memory deficits in mice.

Background: Pharmacotherapies targeting motivational aspects of feeding and palatable food reward, while sparing mood and cognitive function, represent an alluring approach to reverse obesity and maintain weight loss in an obesogenic environment. A novel glucagon-like peptide-1/dexamethasone (GLP-1/Dexa) conjugate, developed to selectively activate glucocorticoid receptors in GLP-1 receptor-expressing cells was shown to decrease food intake and lower body weight in obese mice. Here, we investigate if this novel drug candidate modulates the rewarding properties of food and if it affects behavioral indices of mood and memory.

Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat.

Objective: The incidence of depression is significantly compounded by obesity. Obesity arising from excessive intake of high-fat food provokes anxiodepressive behavior and elicits molecular adaptations in the nucleus accumbens (NAc), a region well-implicated in the hedonic deficits associated with depression and in the control of food-motivated behavior. To determine the etiology of diet-induced depression, we studied the impact of different dietary lipids on anxiodepressive behavior and metabolic and immune outcomes and the contribution of NAc immune activity.

Oleic Acid in the Ventral Tegmental Area Inhibits Feeding, Food Reward, and Dopamine Tone.

Long-chain fatty acids (FAs) act centrally to decrease food intake and hepatic glucose production and alter hypothalamic neuronal activity in a manner that depends on FA type and cellular transport proteins. However, it is not known whether FAs are sensed by ventral tegmental area (VTA) dopamine (DA) neurons to control food-motivated behavior and DA neurotransmission. We investigated the impact of the monounsaturated FA oleate in the VTA on feeding, locomotion, food reward, and DA neuronal activity and DA neuron expression of FA-handling proteins and FA uptake.

Saturated high-fat feeding independent of obesity alters hypothalamus-pituitary-adrenal axis function but not anxiety-like behaviour.

Overconsumption of dietary fat can elicit impairments in emotional processes and the response to stress. While excess dietary lipids have been shown to alter hypothalamus-pituitary-adrenal (HPA) axis function and promote anxiety-like behaviour, it is not known if such changes rely on elevated body weight and if these effects are specific to the type of dietary fat. The objective of this study was to investigate the effect of a saturated and a monounsaturated high-fat diet (HFD) on HPA axis function and anxiety-like behaviour in rats.