Biology subjects

Kanoski, S. E.

Publications and source records attributed to Kanoski, S. E..

At least 19 recordsLinked to original sources

bioRxiv2026

Nutrient-dependent hippocampus dopamine signaling enhances meal-related episodic memory and reduces food intake

BackgroundDopamine (DA) is a neurotransmitter critically involved in food-related reinforcement learning. While mesolimbic DA reward-associated signaling in the nucleus accumbens has been widely investigated, far less is known about DA function in the hippocampus (HPC), a brain region traditionally known for its role in episodic and spatial memory processes that has recently been associated with appetite and food intake control. MethodsHere we investigated dorsal HPC DA signaling dynamics in rats using fiber photometry to detect changes in DA binding (via GRAB-DA sensors) before, during, and after a meal consumption in food-restricted rats. Pharmacological studies targeting HPC dopamine 2 receptors (D2R) assessed the functional role of HPC DA signaling in food intake and meal-related memory processes. ResultsHPC DA binding was significantly elevated in the post-meal relative to the pre-meal state following standard chow consumption. This effect was replicated after consuming a high fat diet or liquid sucrose, but not a low-calorie sweetener. These post-meal DA signaling elevations are dependent on nutrient consumption, as HPC DA binding levels were unaffected by intraperitoneal administration of glucose or the satiation hormone, cholecystokinin, in otherwise fasted rats. Direct HPC D2R agonists administration reduced food intake, whereas HPC D2R blockade after a meal reduced the latency to the next meal and impaired spatial memory for meal location without affecting spatial memory for object location. ConclusionsCollective results identify HPC DA-D2R signaling as a candidate neurobiological mechanism through which nutrient consumption promotes meal-related episodic memory formation, and by extension, reduces subsequent food intake.

neuroscience↗

bioRxiv2026

Transsynaptic neural circuit mapping of ventral hippocampus motivational control systems

The ventral hippocampus contributes to food intake regulation and a range of motivational and memory processes, and its dysfunction is associated with several cognitive and behavioral disorders. However, its circuit-level organization remains incompletely understood. Ventral CA1 (CA1v) neurons send projections to several regions involved in motivational control. Here we focus on three major forebrain targets: the nucleus accumbens shell (ACBsh), medial prefrontal cortex (mPFC), and lateral hypothalamic area (LHA). We mapped the upstream and downstream circuitry of CA1v neurons defined by their projections to these target regions in rats using complementary transsynaptic anterograde and retrograde viral tracing approaches. Monosynaptic outputs to ACBsh, mPFC, and LHA were targeted using ATLAS, a novel transsynaptic anterograde viral approach that drives Cre recombinase in neurons receiving glutamatergic synaptic transmission from the CA1v. Second-order projections arising from these defined pathways were then mapped using a Cre-dependent anterograde viral tracing strategy. In parallel, upstream inputs to CA1v neurons projecting to each downstream target were mapped using a conditional retrograde glycoprotein-deleted rabies viral approach. Anterograde tracing revealed both shared and pathway-specific second-order targets, including bidirectional CA1v projections. Retrograde tracing confirmed expected inputs (e.g., CA3) and uncovered previously unrecognized cortical sources that differed across downstream projection-defined CA1v subpopulations. Together, these findings delineate pathway-specific, multinode circuits linking CA1v neurons to key motivational systems that may inform future therapeutic strategies for disorders involving ventral hippocampal dysfunction.

neuroscience↗

bioRxiv2026

Consumption of processed foods impairs memory function through dietary advanced glycation end-products

Consumption of processed foods is associated with dementia, obesity, and other negative health outcomes. Sustained heat treatment, a common food processing approach to enhance flavor, induces the chemical Maillard reaction that promotes the formation of dietary advanced glycation end-products (AGEs). The neurocognitive impacts of consuming dietary AGEs are poorly understood. Here we modeled an AGE-rich diet through heat treatment fed to rats during adolescence, a critical period of neural development, to mechanistically evaluate the long-term impact of early life dietary AGEs on behavioral and neural processes. Consuming the AGE-rich diet impaired hippocampal-dependent memory function and altered the gut microbiome without inducing obesity or nonspecific behavioral deficits. AGE-induced memory deficits were coupled with impaired hippocampal glutamatergic synaptic neurotransmission and altered expression in the synapse-pruning complement system. Hippocampal synaptic deficits likely result from direct AGE-complement interactions, as our extended studies reveal competitive antagonist action of AGEs on complement receptors. Memory impairments were prevented by administration of the AGE-inhibitor, alagebrium, and by supplementation with an AGE-inhibiting bacterial taxon, Lactococcus lactis, which was depleted in the heat-treated diet. These findings reveal a functional connection between early life dietary AGEs, the microbiome, and memory impairments, thus illuminating mechanisms through which food processing negatively impacts neurocognition.

neuroscience↗

bioRxiv2025

A ventral hippocampus to nucleus accumbens pathway regulates impulsivity

Heightened impulsivity is attributed with substance abuse disorders, gambling, and obesity. The ventral hippocampus (vHPC) has recently been linked with impulse control, yet the neurobiological and behavioral mechanisms through which this control occurs are unknown. A subset of vHPC neurons project to the nucleus accumbens (ACB), a brain region known for regulating reward and motivation. Here, we evaluated the role of vHPC-ACB signaling in food-directed impulsivity using fiber photometry and transsynaptic chemogenetic and behavioral approaches. Male and female rats were trained in the differential reinforcement of low rates of responding (DRL) test of impulsive action, where they learn to withhold lever presses for 20 seconds to obtain a palatable food reward. Photometry recordings during DRL revealed analogous elevations in calcium-dependent activity in the vHPC and ACB during the 5s immediately prior to a non-impulsive vs. an impulsive response. Chemogenetic silencing of ACB-projecting vHPC neurons elevated impulsive responses in DRL relative to vehicle treatment in males but not females, yet had no effect on home cage food intake, operant-based motivation to work for palatable food, impulsive choice, or anxiety-like behavior. To determine whether this impulse control circuit requires vHPC->ACB communication independent of collateral targets of ACB-projecting vHPC neurons, we utilized a novel transsynaptic viral approach to selectively silence ACB neurons that receive synaptic glutamatergic signaling from the vHPC. Results reveal that inhibition of ACB neurons receiving vHPC signaling elevates impulsive action in the DRL task relative to vehicle treatment. Collective results reveal a hippocampal-striatal circuit that regulates impulsive action in males.

neuroscience↗

bioRxiv2025

Early life food insecurity impairs memory function during adulthood

Approximately 14% of U.S. households are estimated to be food insecure. The neurocognitive and metabolic impacts of unpredictable food access during early-life periods of development are poorly understood. To address these gaps we devised a novel rat model of food insecurity to control the timing, type, and quantity of accessible food using programmable feeders. Male rats were divided into 3 groups: Secure-chow (SC), a control group given 100% of daily caloric needs, distributed evenly across 4 daily meals of standard chow at set mealtimes; Secure-mixed (SM), a 2nd control group identical to the SC group except that the food type predictably alternated daily between chow and a high-fat, high-sugar diet (HFHS); and Insecure-mixed (IM), the experimental group given randomly alternating daily access to either chow or HFHS at either 85% or 115% of daily caloric needs, distributed evenly across 3 daily meals with unpredictable mealtimes. These feeding schedules were implemented from postnatal days (PNs) 26-45, after which all groups received chow ad libitum. Metabolic assessments performed in adulthood revealed no group differences in caloric intake, body weight, or body composition when maintained on either chow (PN46-149) or a cafeteria diet (PN150-174). Behavioral measures (PN66-126) revealed no group differences in anxiety-like, exploratory, or impulsive behavior (zero maze, open field, differential reinforcement of low rates of responding procedures). However, the IM group exhibited hippocampus-dependent memory impairments compared to both control groups in the novel location recognition test. These findings suggest that early-life food insecurity may contribute to long-term impairments in memory function.

neuroscience↗

bioRxiv2025

The vagus nerve promotes memory via septo-hippocampal acetylcholine: Implications for obesity-induced cognitive dysfunction

The vagus nerve relays critical metabolic information between the gastrointestinal (GI) tract and the brain. Recent findings highlight a role for vagus nerve-mediated gut-brain signaling in regulating higher-order cognitive processes, although the underlying mechanisms remain poorly understood. Here we demonstrate that nutrient consumption promotes hippocampal-dependent memory function via vagus nerve-mediated acetylcholine (ACh) release in the dorsal hippocampus (HPCd) from medial septum (MS) neurons. In vivo analyses reveal that HPCd ACh release is engaged during nutrient consumption, and that this response is abolished in animals that received MS cholinergic neuron ablation, subdiaphragmatic vagotomy (SDV), or early-life Western Diet (WD) maintenance. MS cholinergic neuron ablation, SDV, and early-life WD also impaired memory for meal location, suggesting that this gut-brain pathway functions to encode memories for eating events. Collectively, results identify a neurobiological mechanism whereby nutrient consumption promotes memory function, and reveal that disruption of this vagal-brain signaling system mediates WD-associated memory impairments.

neuroscience↗

bioRxiv2025

Endotoxemia-induced inflammation in the absence of obesity decreases anxiety-like and impulsive behavior without affecting learning and memory

Obesity is associated with increased gut permeability, which contributes to a state of chronic low-grade inflammation. Obesity is also linked with altered neurocognitive functions, including impaired learning and memory. Whether these changes are secondary to neuroinflammation vs. other comorbidities associated with obesity is unknown. Here, we modeled the chronic low-grade inflammation that accompanies diet-induced obesity, but in the absence of obesity or consumption of an obesogenic diet. Male rats were implanted with intraperitoneal osmotic minipumps, continuously dispensing either saline (control) or lipopolysaccharide (LPS), an endotoxin produced in the gut that triggers inflammation when in circulation. Immunohistochemistry results revealed that LPS exposure led to neuroinflammation, with an increased number of Ionized Calcium-Binding Molecule 1 (Iba1+) cells in the amygdala and hippocampus in LPS rats vs. controls. Given that these brain regions are associated with impulse control, anxiety-like behavior, and learning and memory, we tested whether chronic LPS treatment impacted these behaviors. Interestingly, LPS exposure did not affect hippocampal-dependent memory in the Morris water maze, novel location recognition, or novel object in context memory tests, suggesting that neuroinflammation in the absence of obesity does not induce memory impairments. Further, chronic LPS significantly decreased anxiety-like behavior in the open field test and food impulsivity in an operant-based procedure. LPS animals also had significantly lower corticosterone and melatonin levels when compared to controls, which may contribute to these behavioral outcomes. These results suggest that the low-grade inflammation associated with obesity is not driving obesity-associated memory impairments but does reduce anxiety and food-motivated impulsive responses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/654970v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@788648org.highwire.dtl.DTLVardef@b7fce8org.highwire.dtl.DTLVardef@13cf526org.highwire.dtl.DTLVardef@102c19c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

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. To address this, we targeted OT neuron-specific designer receptors exclusively activated by designer drugs (DREADDs) in either the PVH or SON in rats, thus allowing for evaluation of food intake following selective activation of OT neurons separately in each nucleus. Results revealed that DREADDs-mediated excitation of PVH OT neurons reduced consumption of both standard chow and a high fat high sugar diet (HFHS) via reductions in meal size. On the contrary, SON OT neuron activation had the opposite effect by increasing both standard chow and liquid sucrose consumption, with the former effect mediated by an increase in meal size. To further examine the physiological role of OT neurons in eating behavior, a viral-mediated approach was used to silence synaptic transmission of OT neurons separately in either the PVH or SON. Results from these studies revealed that PVH OT neuron silencing significantly increased consumption of HFHS by increasing meal size whereas SON OT neuron silencing reduced chow consumption by decreasing meal size. Collectively these data reveal that PVH and SON OT neurons differentially modulate food intake by either increasing or decreasing satiation signaling, respectively.

neuroscience↗

bioRxiv2024

Hippocampus oxytocin signaling promotes prosocial eating in rats

The hypothalamic neuropeptide oxytocin (OT) influences both food intake and social behavior. Given that food preference and consumption are heavily affected by social factors in mammals, it is critical to understand the extent that OTs role in regulating these two fundamental behaviors is interconnected. Here we evaluated the role of OT signaling in the dentate gyrus of the dorsal hippocampus (HPCd), a brain region recently linked with eating and social memory, on food preference and consumption in rats under conditions that vary with regards to social presence and conspecific familiarity. Results from neuropharmacological and virogenetic knockdown approaches reveal that HPCd OT signaling promotes eating in the presence of a familiar but not an unfamiliar conspecific. Additionally, HPCd OT receptor signaling is required for the social transmission of food preference. These findings collectively identify the HPCd as a novel substrate where oxytocin synergistically influences eating and social behaviors.

neuroscience↗

bioRxiv2023

Early- but not late-adolescent Western diet consumption programs for long-lasting memory impairments in male but not female rats

Early life Western diet (WD) consumption leads to impaired memory function, particularly for processes mediated by the hippocampus. However, the precise critical developmental window(s) during which WD exposure negatively impacts hippocampal function are unknown. Here, we exposed male and female rats to a WD model involving free access to a variety of high-fat and/or high-sugar food and drink items during either the early-adolescent period (postnatal days [PN] 26-41; WD-EA) or late-adolescent period (PN 41-56; WD-LA). Control (CTL) rats were given healthy standard chow throughout both periods. To evaluate long-lasting memory capacity well beyond the early life WD exposure periods, we performed behavioral assessments after both a short (4 weeks for WD-EA, 2 weeks for WD-LA) and long (12 weeks for WD-EA, 10 weeks for WD-LA) period of healthy diet intervention. Results revealed no differences in body weight or body composition between diet groups, regardless of sex. Following the shorter period of healthy diet intervention, both male and female WD-EA and WD-LA rats showed deficits in hippocampal-dependent memory compared to CTL rats. Following the longer healthy diet intervention period, memory impairments persisted in male WD-EA but not WD-LA rats. In contrast, in female rats the longer healthy diet intervention reversed the initial memory impairments in both WD-EA and WD-LA rats. Collectively, these findings reveal that early-adolescence is a critical period of long-lasting hippocampal vulnerability to dietary insults in male but not female rats, thus highlighting developmental- and sex-specific effects mediating the relationship between the early life nutritional environment and long-term cognitive health.

animal behavior and cognition↗

bioRxiv2023

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). Behavioral, metabolic, and microbiome assessments were performed both before and after a 30-day healthy diet intervention beginning at early adulthood. Results revealed CAF-induced HPC-dependent contextual episodic memory impairments that persisted despite healthy diet intervention, whereas CAF was not associated with long-term changes in body weight, body composition, glucose tolerance, anxiety-like behavior, or gut microbiome. HPC immunoblot analyses after the healthy diet intervention identified reduced levels of vesicular ACh transporter in CAF vs. CTL rats, indicative of chronically reduced HPC ACh tone. To determine whether these changes were functionally related to memory impairments, we evaluated temporal HPC ACh binding via ACh-sensing fluorescent reporter in vivo fiber photometry during memory testing, as well as whether the memory impairments could be rescued pharmacologically. Results revealed dynamic HPC ACh binding during object-contextual novelty recognition was highly predictive of memory performance and was disrupted in CAF vs. CTL rats. Further, HPC alpha-7 nicotinic receptor agonist infusion during consolidation rescued memory deficits in CAF rats. Overall, these findings identify dysregulated HPC ACh signaling as a mechanism underlying early life WD-associated memory impairments.

neuroscience↗

bioRxiv2022

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

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. Specifically, our results reveal that MCH neuron Ca+2 activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally-relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes.

neuroscience↗

bioRxiv2022

Early life low-calorie sweetener consumption impacts energy balance during adulthood

Children frequently consume beverages sweetened with either 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). SSB or LCS consumption was voluntary and restricted within federal recommended daily limits. When subsequently maintained on a cafeteria-style junk food diet (CAF; various high-fat, high-sugar foods) during adulthood, ACE-K-exposed rats demonstrated reduced caloric consumption vs. controls, which contributed to lower body weights in female but not male ACE-K rats. These discrepant intake and body weight effects in male ACE-K rats are likely based on reduced gene expression of thermogenic indicators (UCP1, BMP8B) in brown adipose tissue. Female stevia-exposed rats did not differ from controls in caloric intake or body weight, yet they consumed more SSB during adult CAF exposure. No SSB-exposed rats, neither male nor female, differed from controls in adult total caloric consumption or body weight measures. Collective results reveal that early life LCS consumption alters sugar preference, body weight, and gene expression for markers of thermogenesis during adulthood, with both sex- and sweetener-dependent effects.

physiology↗

bioRxiv2021

Lasting effects of low-calorie sweeteners on glucose regulation, sugar intake, and memory

Low-calorie sweetener (LCS) consumption in children has increased due to widespread LCS presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the impact of early-life LCS consumption are lacking. Therefore, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, gut microbiome, neural, and behavioral outcomes. Results reveal that habitual early-life LCS consumption disrupts post-oral glucose tolerance and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, LCS consumption reduces lingual sweet taste receptor expression and alters sugar-motivated appetitive and consummatory responses. RNA sequencing analyses reveal that LCS also impacts collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results suggest that regular early-life LCS consumption yields long-lasting impairments in metabolism, sugar-motivated behavior, and hippocampal-dependent memory.

neuroscience↗

bioRxiv2021

Early life Western diet-induced memory impairments and gut microbiome changes in female rats are long-lasting despite healthy dietary intervention

ObjectiveConsumption of a Western diet during adolescence results in hippocampus (HPC)-dependent memory impairments and gut microbiome dysbiosis. Whether these adverse outcomes are reversible in adulthood following intervention with a healthy diet is unknown. Here we assessed the short- and long-term effects of adolescent consumption of a Western diet enriched with either sugar alone, or sugar and fat on metabolic outcomes, HPC-dependent memory, and gut microbiota. MethodsAdolescent female rats (PN 26) were fed a standard chow diet (CTL), a chow diet with access to 11% sugar solution (SUG), or a junk food cafeteria-style diet (CAF) containing a variety of fat- and/or sugar-enriched foods. During adulthood (PN 65+), metabolic outcomes, HPC-dependent memory, and gut microbial populations were evaluated both before and after a 5-week dietary intervention period where all groups were fed a diet of water standard chow. ResultsPrior to the dietary intervention both the CAF and SUG groups demonstrated impaired HPC-dependent memory, increased adiposity, and altered gut microbial populations relative to controls. However, impaired peripheral glucose regulation was only observed in the SUG group. The dietary intervention reversed the metabolic dysfunction in both the CAF and SUG groups, whereas HPC-dependent memory impairments were reversed in the SUG, but not the CAF group. The composition of the gut microbiota remained distinct from controls in both groups after dietary intervention. ConclusionsWhile the metabolic impairments associated with adolescent cafeteria diet consumption are reversible in adulthood with dietary intervention, the HPC-dependent memory impairments and the gut microbiome dysbiosis persist.

developmental biology↗

bioRxiv2020

Central oxytocin signaling inhibits food reward-motivated behaviors and VTA dopamine responses to food-predictive cues

Oxytocin potently reduces food intake and is a potential target system for obesity treatment. A better understanding of the behavioral and neurobiological mechanisms mediating oxytocins anorexigenic effects may guide more effective obesity pharmacotherapy development. The present study examined the effects of central (lateral intracerebroventricular [ICV]) administration of oxytocin in rats on motivated responding for palatable food. Various conditioning procedures were employed to measure distinct appetitive behavioral domains, including food seeking in the absence of consumption (conditioned place preference expression), impulsive responding for food (differential reinforcement of low rates of responding), effort-based appetitive decision making (high-effort palatable vs. low-effort bland food), and postingestive reward value encoding (incentive learning). Results reveal that ICV oxytocin potently reduces food-seeking behavior, impulsivity, and effort-based palatable food choice, yet does not influence encoding of postingestive reward value in the incentive learning task. To investigate a potential neurobiological mechanism mediating these behavioral outcomes, we utilized in vivo fiber photometry in ventral tegmental area (VTA) dopamine neurons to examine oxytocins effect on phasic dopamine neuron responses to sucrose-predictive Pavlovian cues. Results reveal that ICV oxytocin significantly reduced food cue-evoked dopamine neuron activity. Collectively, these data reveal that central oxytocin signaling inhibits various obesity-relevant conditioned appetitive behaviors, potentially via reductions in food cue-driven phasic dopamine neural responses in the VTA. HighlightsO_LICentral oxytocin inhibits motivated responding for palatable food reinforcement C_LIO_LICentral oxytocin does not play a role in encoding postingestive reward value C_LIO_LICentral oxytocin blunts VTA dopamine neuron activity in response to food cues C_LI

neuroscience↗

bioRxiv2020

Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

Vagal afferent neuron (VAN) signaling sends information from the gut to the brain and is fundamental in the neural control of feeding behavior and metabolism. Recent findings reveal that VAN signaling also plays a critical role in cognitive processes, including hippocampus (HPC)-dependent memory. VANs, located in nodose ganglia, express receptors for various gut-derived endocrine signals, however, the function of these receptors with regards to feeding behavior, metabolism, and memory control is poorly understood. We hypothesized that VAN-mediated processes are influenced by ghrelin, a stomach-derived orexigenic hormone, via communication to its receptor (growth hormone secretagogue receptor [GHSR]) expressed on gut-innervating VANs. To examine this hypothesis, rats received nodose ganglia injections of an adeno-associated virus (AAV) expressing short hairpin RNAs targeting GHSR (or a control AAV) for RNA interference-mediated VAN-specific GHSR knockdown. Results reveal that VAN GHSR knockdown induced various feeding and metabolic disturbances, including increased meal frequency, impaired glucose tolerance, delayed gastric emptying, and increased body weight compared to controls. Additionally, VAN-specific GHSR knockdown impaired HPC-dependent episodic contextual memory and reduced HPC brain-derived neurotrophic factor expression, but did not affect anxiety-like behavior or levels of general activity. A functional role for endogenous VAN GHSR signaling was further confirmed by results revealing that VAN signaling is required for the hyperphagic effects of ghrelin administered at dark onset, and that gut-restricted ghrelin-induced increases in VAN firing rate require intact VAN GHSR expression. Collective results reveal that VAN GHSR signaling is required for both normal feeding and metabolic function as well as HPC-dependent memory.

neuroscience↗

bioRxiv2020

Hippocampus-lateral septum circuitry mediates memory for food location in rats

Remembering the location of a food or water source is essential for survival. Here we demonstrate 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 downstream lateral septum (LS) signaling, as both reversible and chronic disconnection of HPCv (field CA1) to LS signaling impairs spatial memory retention for the location of either food or water reinforcement. This neural pathway selectively encodes appetitive spatial memory, as HPCv-LS disconnection does not affect aversive reinforcement-based spatial memory in an escape task using the same apparatus. The selectivity of this pathway in promoting foraging-related memory is further supported by results showing that CA1v-LS disconnection does not affect food intake, motivated operant responses for food, anxiety-like behavior, locomotor activity, or social and olfactory-based appetitive learning. Fluorescent in situ hybridization reveals that LS neurons recruited during the appetitive spatial memory task are primarily GABAergic, and multisynaptic anterograde neural pathway tracing and immediate early gene mapping identify the lateral hypothalamic area as a functional downstream target of this pathway. Collective results reveal a novel neural circuit through which the hippocampus selectively mediates memory for the location of appetitive (food or water) but not aversive (escape) reinforcement.

neuroscience↗