Biology subjects

Klug, M. E.

Publications and source records attributed to Klug, M. E..

3 recordsLinked to original sources

bioRxiv2023

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. These HPCv meal-responsive neurons project to the lateral hypothalamic area (LHA) and single-nucleus RNA sequencing and in situ hybridization analyses indicate they are enriched in serotonin 2a receptors (5HT2aR). Either chemogenetic silencing of HPCv-to-LHA projections or intra-HPCv 5HT2aR antagonist yielded foraging-related spatial memory deficits, as well as alterations in caloric intake and the temporal sequence of spontaneous meal consumption. Collective results identify a population of HPCv neurons that dynamically respond to eating to encode meal-related memories.

neuroscience↗

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

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↗