Physiology, Pharmacology, Memory, Stress, Social behavior, Reward
12
Scopus Publications
Scopus Publications
Dietary protein restriction in rats leads to a rapid within-session preference for protein Giulia Chiacchierini, Fabien Naneix, John Apergis-Schoute, James E McCutcheon Physiology and Behavior, 2025 Evolution has provided species with adaptive behavioural mechanisms that guarantee tight dietary protein regulation. However, an unsolved question is whether the well-established preference for protein-containing food manifested during states of protein restriction is innate or learned. Here, we tackled this problem by maintaining male rats on either a low-protein diet (4 % protein, protein-restricted) or a control diet (22 % protein, non-restricted) for 9-12 days, and then offered them two novel foods, a protein-containing solution (4 % casein) and a carbohydrate-containing solution (4 % maltodextrin) during a daily 60-minute free-choice test, repeated for 5 consecutive days. We assessed both the total and cumulative intake of each solution throughout each test, as well as the microstructure of licking behaviour as an index of the solutions' palatability. In a second experiment, we exposed a different cohort of rats, before any behavioural test, to the same protein source (i.e., casein) that they would encounter during the free-choice tests, to assess whether familiarity with casein would drive subsequent casein intake even in non-restricted rats. We found that dietary protein restriction leads to a rapid preference (within 5 min of first exposure) for a casein-rich solution, and this preference is persistent over subsequent exposures. Increased palatability of protein during initial exposure correlated with protein preference in the restricted rats. Moreover, familiarity with casein did not lead to protein preference in non-restricted rats. This study demonstrates that, when in need of protein, protein preference is a rapid adaptation that requires minimal experience of protein.
A behavioral screening method for predicting PTSD-like phenotypes: Novel application to female rats Giulia Chiacchierini, Giulia Federica Mancini, Benedetta Di Cesare, Luca Romanelli, Maria Morena, Patrizia Campolongo Journal of Neuroscience Methods, 2025 BACKGROUND: Only a small percentage of trauma-exposed subjects develop PTSD, with females being twice as likely. Most rodent models focus on males and fail to account for inter-individual variability in females. NEW METHOD: We tested a behavioral PTSD model in female rats to distinguish between susceptible and resilient individuals. In Experiment 1, female rats underwent footshocks paired with social isolation, a PTSD risk factor. They were re-exposed to the conditioned context to test memory retention, and assessed in the Elevated Plus Maze (EPM) and Social Interaction (SI) tests for anxiety and social behavior. RESULTS: Footshock-exposed rats showed fear memory retention up to 16 days, indicated by elevated freezing behavior during re-exposure. They also exhibited reduced exploration in the EPM and less SI time compared to controls. In Experiment 2, we classified rats into normal responders, susceptible, and resilient groups based on locomotor activity after trauma, correlating with memory retention and anxiety. COMPARISON WITH EXISTING METHODS: Unlike existing models focused on males and lacking predictive variables before trauma, our method identifies PTSD-like susceptibility and resilience in female rats by using exploratory behavior as a predictor before trauma exposure. CONCLUSIONS: Exploratory activity in a novel environment after trauma and before extinction is a reliable predictor of PTSD-like phenotypes and differentiates between susceptible and resilient female rats.
Treating Alzheimer's disease with brain stimulation: From preclinical models to non-invasive stimulation in humans Ilenia Lanni, Giulia Chiacchierini, Costanza Papagno, Valerio Santangelo, Patrizia Campolongo Neuroscience and Biobehavioral Reviews, 2024 Alzheimer's disease (AD) is a severe and progressive neurodegenerative condition that exerts detrimental effects on brain function. As of now, there is no effective treatment for AD patients. This review explores two distinct avenues of research. The first revolves around the use of animal studies and preclinical models to gain insights into AD's underlying mechanisms and potential treatment strategies. Specifically, it delves into the effectiveness of interventions such as Optogenetics and Chemogenetics, shedding light on their implications for understanding pathophysiological mechanisms and potential therapeutic applications. The second avenue focuses on non-invasive brain stimulation (NiBS) techniques in the context of AD. Evidence suggests that NiBS can successfully modulate cognitive functions associated with various neurological and neuropsychiatric disorders, including AD, as demonstrated by promising findings. Here, we critically assessed recent findings in AD research belonging to these lines of research and discuss their potential impact on the clinical horizon of AD treatment. These multifaceted approaches offer hope for advancing our comprehension of AD pathology and developing novel therapeutic interventions.
Involvement of A13 dopaminergic neurons in prehensile movements but not reward in the rat Celia Garau, Jessica Hayes, Giulia Chiacchierini, James E. McCutcheon, John Apergis-Schoute Current Biology, 2023 Tyrosine hydroxylase (TH)-containing neurons of the dopamine (DA) cell group A13 are well positioned to impact known DA-related functions as their descending projections innervate target regions that regulate vigilance, sensory integration, and motor execution. Despite this connectivity, little is known regarding the functionality of A13-DA circuits. Using TH-specific loss-of-function methodology and techniques to monitor population activity in transgenic rats in vivo, we investigated the contribution of A13-DA neurons in reward and movement-related actions. Our work demonstrates a role for A13-DA neurons in grasping and handling of objects but not reward. A13-DA neurons responded strongly when animals grab and manipulate food items, whereas their inactivation or degeneration prevented animals from successfully doing so-a deficit partially attributed to a reduction in grip strength. By contrast, there was no relation between A13-DA activity and food-seeking behavior when animals were tested on a reward-based task that did not include a reaching/grasping response. Motivation for food was unaffected, as goal-directed behavior for food items was in general intact following A13 neuronal inactivation/degeneration. An anatomical investigation confirmed that A13-DA neurons project to the superior colliculus (SC) and also demonstrated a novel A13-DA projection to the reticular formation (RF). These results establish a functional role for A13-DA neurons in prehensile actions that are uncoupled from the motivational factors that contribute to the initiation of forelimb movements and help position A13-DA circuits into the functional framework regarding centrally located DA populations and their ability to coordinate movement.
Restriction of dietary protein in rats increases progressive-ratio motivation for protein Giulia Chiacchierini, Fabien Naneix, John Apergis-Schoute, James E. McCutcheon Physiology and Behavior, 2022 Low-protein diets can impact food intake and appetite, but it is not known if motivation for food is changed. In the present study, we used an operant behavioral task - the progressive ratio test - to assess whether motivation for different foods was affected when rats were maintained on a protein-restricted diet (REST, 5% protein diet) compared to non-restricted control rats (CON, 18% protein). Rats were tested either with nutritionally-balanced pellets (18.7% protein, Experiment 1) or protein-rich pellets (35% protein, Experiment 2) as reinforcers. Protein restriction increased breakpoint for protein-rich pellets, relative to CON rats, whereas no difference in breakpoint for nutritionally-balanced pellets was observed between groups. When given free access to either nutritionally-balanced pellets or protein-rich pellets, REST and CON rats did not differ in their intake. We also tested whether a previous history of protein restriction might affect present motivation for different types of food by assessing breakpoint of previously REST animals that were subsequently put on standard maintenance chow (protein-repleted rats, REPL, Experiment 2). REPL rats did not show increased breakpoint, relative to their initial encounter with protein-rich pellets while they were protein-restricted. This study demonstrates that restriction of dietary protein induces a selective increased motivation for protein-rich food, a behavior that disappears once rats are not in need of protein.
Predictive and motivational factors influencing anticipatory contrast: A comparison of contextual and gustatory predictors in food restricted and free-fed rats Jessica Hayes, Celia Garau, Giulia Chiacchierini, Gonzalo P. Urcelay, James E. McCutcheon, John Apergis-Schoute Physiology and Behavior, 2021 In anticipation of palatable food, rats can learn to restrict consumption of a less rewarding food type resulting in an increased consumption of the preferred food when it is made available. This construct is known as anticipatory negative contrast (ANC) and can help elucidate the processes that underlie binge-like behavior as well as self-control in rodent motivation models. In the current investigation we aimed to shed light on the ability of distinct predictors of a preferred food choice to generate contrast effects and the motivational processes that underlie this behavior. Using a novel set of rewarding solutions, we directly compared contextual and gustatory ANC predictors in both food restricted and free-fed Sprague-Dawley rats. Our results indicate that, despite being food restricted, rats are selective in their eating behavior and show strong contextually-driven ANC similar to free-fed animals. These differences mirrored changes in palatability for the less preferred solution across the different sessions as measured by lick microstructure analysis. In contrast to previous research, predictive cues in both food restricted and free-fed rats were sufficient for ANC to develop although flavor-driven ANC did not relate to a corresponding change in lick patterning. These differences in the lick microstructure between context- and flavor-driven ANC indicate that the motivational processes underlying ANC generated by the two predictor types are distinct. Moreover, an increase in premature port entries to the unavailable sipper - a second measure of ANC - in all groups reveals a direct influence of response competition on ANC development.
Protein appetite drives macronutrient-related differences in ventral tegmental area neural activity Giulia Chiacchierini, Fabien Naneix, Kate Zara Peters, John Apergis-Schoute, Eelke Mirthe Simone Snoeren, James Edgar McCutcheon Journal of Neuroscience, 2021 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 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 elevated 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 animals to acquire an adequate amount of protein in their diet. SIGNIFICANCE STATEMENT Acquiring insufficient protein in one's 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 VTA, 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.