Biology subjects

Peters, K. Z.

Publications and source records attributed to Peters, K. Z..

8 recordsLinked to original sources

bioRxiv2026

Long lasting alterations of feeding by adolescent obesity

The prevalence of obesity is increasing worldwide, especially amongst younger populations. As both brain and body are still under development, numerous studies have shown that adolescence is an especially sensitive period for the impact of external insults including unbalanced diets. To better understand and prevent the vulnerability to obesity and maladaptive food choice, it is crucial to explore the long-term impact of adolescent exposure to obesogenic diets on different feeding behaviours. To address this, we gave mice access to an obesogenic diet with a very high-fat content (vHFD) specifically during adolescence and investigated the long-lasting impact on feeding at adulthood months after a switch to a healthy diet. Using specific feeding tests, we found that both males and females vHFD-exposed mice exhibited an increased intake of both standard food and palatable high-fat foods, without impacting preference for non-caloric food rewards. Importantly, these sex-dependent alterations are not fully correlated with diet-induced weight gain but may support long-term vulnerability to overeating and the development or maintenance of obesity.

neuroscience↗

bioRxiv2026

Adolescent obesity induces sex-specific alterations of action control

The prevalence of obesity is rising worldwide in young people and is associated with poor long-term health outcomes. To counter obesity, weight loss strategies especially involve changes in feeding behaviors and food choice. However, the high level of relapse to unhealthy dietary habits represents an important challenge, suggesting long-term alterations of decision-making and food-seeking processes. Previous studies showed that adolescence is critical for the development of decision-making functions. Thus, it is essential to understand the precise impact of the exposure to obesogenic diets during this life stage on the different processes underlying flexible control of food-seeking actions. To address this, we gave mice access to high-fat diets (HFDs) with different fat contents during adolescence and investigated the long-lasting impact on action control at adulthood after a switch to a healthy diet. We uncovered important sex differences. In both males and females, exposure to HFD with very high-fat content (60%) promoted habitual behavior, which is less flexible to adapt to changes in outcome value or action-outcome relationships. In contrast, exposure to HFD with lower fat content (45%) impaired action control based on the updating of outcome value in males only, while impairing action control based on the updating of action-outcome relationships in females only. These findings highlight how the consumption of obesogenic diets during adolescence has long-lasting, diet- and sex-dependent effects on decision-making processes, promoting habitual responses to food. These changes may support long-term vulnerability for mental and physiological health conditions. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/702500v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@73aab1org.highwire.dtl.DTLVardef@1cb8110org.highwire.dtl.DTLVardef@1866a5dorg.highwire.dtl.DTLVardef@1b11d2c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Food seeking suppression by environmental enrichment accompanies cell type- and circuit-specific prelimbic cortical modulation

Cues such as fast-food advertisements associated with food can provoke food cravings which may lead to unhealthy overeating. To effectively control such cravings, we need to better understand the factors that reduce food cue reactivity and reveal corresponding anti-craving brain mechanisms. We previously reported that access to environmental enrichment (EE) that provides cognitive and physical stimulation in mice reduced cue-evoked sucrose seeking and prelimbic cortex (PL) neuronal reactivity. To date, the phenotype of PL neurons that undergo EE-induced adaptations has not been fully elucidated. Therefore, we used brain slice electrophysiology to investigate how EE modulated intrinsic excitability in the general population of PL interneurons and pyramidal cells. Additionally, we used retrograde tracing and the neuronal activity marker Fos to investigate how EE modulated cue-evoked recruitment of pyramidal cells projecting to the paraventricular nucleus of the thalamus (PVT) and nucleus accumbens core (NAc). Before the cue-evoked sucrose seeking test, EE enhanced the general, baseline excitability of inhibitory interneurons, but not pyramidal cells, thereby promoting inhibitory overdrive. During cue-evoked sucrose seeking, EE suppressed recruitment of PVT-, but not NAc-projecting, neurons thereby selectively promoting corticothalamic, but not corticoaccumbens, excitatory underdrive. Collectively, we further illuminate EEs anti-food seeking actions whereby EE promotes both cell type-specific (inhibitory interneuron overdrive) and circuit-specific (excitatory corticothalamic underdrive) neuroadaptations in the PL.

neuroscience↗

bioRxiv2025

Prelimbic cortical excitatory overdrive and inhibitory underdrive accompany environmental suppression of food seeking

Cues associated with food, such as fast-food advertising, can provoke food cravings and may lead to unhealthy overeating. Environmental enrichment (EE) that enhances cognitive and physical stimulation can reduce cue-evoked sucrose seeking in mice and recruitment of sucrose cue-reactive neurons or neuronal ensembles in the prelimbic cortex (PL), which regulates appetitive behaviors. Hence, EE provides us with a behavioral model and neuronal targets to identify anti-craving relevant mechanisms. Here, we investigated in the PL how EE modulated neuronal excitability and activity patterns in cue-reactive neuronal populations. Chemogenetic inhibition of cue-reactive neurons in PL blocked cue-evoked sucrose seeking, thereby confirming the function of these neurons in sucrose cue memory. EE boosted the baseline excitability of originally, or before EE exposure, cue-reactive, excitatory pyramidal cells in PL. Furthermore, their sucrose cue-specificity was lost - resulting in their persistent activation and non-cue selective activation or excitatory overdrive. Furthermore, EE reduced recruitment of cue-reactive, inhibitory interneurons reflecting inhibitory underdrive. Taken together, impaired neuronal food cue processing due to simultaneous prefrontal cortical excitatory overdrive and inhibitory underdrive likely underlies EEs anti-craving action, thereby serving as potential neurophysiological targets to develop novel medications that help control food cravings.

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bioRxiv2020

Distracting stimuli evoke ventral tegmental area responses in rats during ongoing saccharin consumption

Disruptions in attention, salience and increased distractibility are implicated in multiple psychiatric conditions. The ventral tegmental area (VTA) is a potential site for converging information about external stimuli and internal states to be integrated and guide adaptive behaviours. Given the dual role of dopamine signals in both driving ongoing behaviours (e.g. feeding) and monitoring salient environmental stimuli, understanding the interaction between these functions is crucial. Here we investigate VTA neuronal activity during distraction from ongoing feeding. We developed a task to assess distraction exploiting self-paced licking in rats. Rats trained to lick for saccharin were given a distraction test, in which three consecutive licks within 1 second triggered a random distractor (e.g. light and tone stimulus). On each trial they were quantified as distracted or not based on the length of their pauses in licking behaviour. We expressed GCaMP6s in VTA neurons and used fibre photometry to record calcium fluctuations during this task as a proxy for neuronal activity. Distractor stimuli caused rats to interrupt their consumption of saccharin, a behavioural effect which quickly habituated with repeat testing. VTA neural activity showed consistent increases to distractor presentations and, furthermore, these responses were greater on distracted trials compared to non-distracted trials. Interestingly, neural responses show a slower habituation than behaviour with consistent VTA responses seen to distractors even after they are no longer distracting. These data highlight the complex role of the VTA in maintaining ongoing appetitive and consummatory behaviours while also monitoring the environment for salient stimuli.

neuroscience↗

bioRxiv2020

AGE DEPENDENT EFFECTS OF PROTEIN RESTRICTION ON DOPAMINE RELEASE

Despite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1-20 Hz). By contrast, protein restriction performed at adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction has no impact on dopamine release when performed at adulthood but in adolescent rats we observed frequency-dependent increases in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages.

neuroscience↗

bioRxiv2019

Protein appetite drives neural activity in the ventral tegmental area

Control of protein intake is essential for numerous biological processes as several amino acids cannot be synthesized de novo, however, its neurobiological substrates are still poorly understood. In the present study, we combined in vivo fiber photometry with nutrient-conditioned flavor in a rat model of protein appetite to record neuronal activity in the ventral tegmental area (VTA), a central brain region for the control of food-related processes. In adult male rats, protein restriction increased preference for casein (protein) over maltodextrin (carbohydrate). Moreover, protein consumption was associated with a greater VTA response relative to carbohydrate. After initial nutrient preference, a switch from a normal balanced diet to protein restriction induced rapid development of protein preference but required extensive exposure to macronutrient solutions to induce greater VTA responses to casein. Furthermore, prior protein restriction induced long-lasting food preference and VTA responses. This study reveals that VTA circuits are involved in protein appetite in times of need, a crucial process for all animals to acquire an adequate amount of protein in their diet. Significance StatementAcquiring insufficient protein in ones diet has severe consequences for health and ultimately will lead to death. In addition, a low level of dietary protein has been proposed as a driver of obesity as it can leverage up intake of fat and carbohydrate. However, much remains unknown about the role of the brain in ensuring adequate intake of protein. Here, we show that in a state of protein restriction a key node in brain reward circuitry, the ventral tegmental area, is activated more strongly during consumption of protein than carbohydrate. Moreover, although rats behavior changed to reflect new protein status, patterns of neural activity were more persistent and only loosely linked to protein status.

neuroscience↗

bioRxiv2017

Restriction of dietary protein leads to conditioned protein preference and elevated palatability of protein-containing food in rats.

The mechanisms by which intake of dietary protein is regulated are poorly understood despite their potential involvement in determining food choice and appetite. In particular, it is unclear whether protein deficiency results in a specific appetite for protein and whether influences on diet are immediate or develop over time. To determine the effects of protein restriction on consumption, preference, and palatability for protein we assessed patterns of intake for casein (protein) and maltodextrin (carbohydrate) solutions in adult rats. To induce a state of protein restriction, rats were maintained on a low protein diet (5% casein) and compared to control rats on non-restricted diet (20% casein). Under these dietary conditions, relative to control rats, protein-restricted rats exhibited hyperphagia without weight gain. After two weeks, on alternate conditioning days, rats were given access to either isocaloric casein or maltodextrin solutions that were saccharin-sweetened and distinctly flavoured whilst consumption and licking patterns were recorded. This allowed rats to learn about the post-ingestive nutritional consequences of the two different solutions. Subsequently, during a preference test when rats had access to both solutions, we found that protein-restricted rats exhibited a preference for casein over carbohydrate whereas non-restricted rats did not. Analysis of lick microstructure revealed that this preference was associated with an increase in cluster size and number, reflective of an increase in palatability. In conclusion, protein-restriction induced a conditioned preference for protein, relative to carbohydrate, and this was associated with increased palatability.

neuroscience↗