Biology subjects

Ferrario, C. R.

Publications and source records attributed to Ferrario, C. R..

6 recordsLinked to original sources

bioRxiv2026

Colony maintenance and the behavioral and physiological characteristics of selectively bred obesity prone and obesity resistant rats.

Obesity arises from interactions between several factors including physiology, environment and genes. Studies in humans have revealed that up to 70% of overweight and obesity can be attributed to biological and genetic factors. Thus, rodent models that capture innate susceptibility or resistance to obesity have been invaluable for disentangling inherent drivers of obesity from neurobiological alterations that occur in response to consumption of obesogenic foods and/or increased adiposity. For example, studies of rats selectively bred for their propensity vs resistance to diet-induced weight gain (DIO and DR) have uncovered differences in hypothalamic circuits involved in leptin signaling and revealed relationships between susceptibility to obesity and motivational response to food cues, as well as inherent and diet-induced alterations in mesocorticolimbic systems that differ between these populations. Maintaining selectively bred lines in a closed breeding population requires the periodic introduction of new genes to avoid inbreeding. Here we describe a process for maintaining these lines, characterize key phenotypes across the selection process and verify weight gain and obesity phenotypes in the resulting colony. In addition, given the central role of the striatum in motivation for food, we examined basal striatal function and food motivation in these refreshed lines using whole-cell patch clamping and instrumental procedures. Key weight and metabolic phenotypes were maintained in the resulting colony, as was enhanced motivation for food in obesity prone rats. This provides a strong basis for examination of interactions between genes, environment and neurobehavioral plasticity that promote weight gain and obesity.

physiology↗

bioRxiv2024

Quantifying social roles in multi-animal videos using subject-aware deep-learning

Analyzing social behaviors is critical for many fields, including neuroscience, psychology, and ecology. While computational tools have been developed to analyze videos containing animals engaging in limited social interactions under specific experimental conditions, automated identification of the social roles of freely moving individuals in a multi-animal group remains unresolved. Here we describe a deep-learning-based system - named LabGym2 - for identifying and quantifying social roles in multi-animal groups. This system uses a subject-aware approach: it evaluates the behavioral state of every individual in a group of two or more animals while factoring in its social and environmental surroundings. We demonstrate the performance of subject-aware deep-learning in different species and assays, from partner preference in freely-moving insects to primate social interactions in the field. Our subject-aware deep learning approach provides a controllable, interpretable, and efficient framework to enable new experimental paradigms and systematic evaluation of interactive behavior in individuals identified within a group.

animal behavior and cognition↗

bioRxiv2023

Effects of junk-food on food-motivated behavior and NAc glutamate plasticity; insights into the mechanism of NAc calcium-permeable AMPA receptor recruitment

In rats, eating obesogenic diets increase calcium-permeable AMPA receptor (CP-AMPAR) transmission in the nucleus accumbens (NAc) core, and enhances food-motivated behavior. Interestingly these diet-induced alterations in NAc transmission are pronounced in obesity-prone (OP) rats and absent in obesity-resistant (OR) populations. However, effects of diet manipulation on food motivation, and the mechanisms underlying NAc plasticity in OPs is unknown. Using male selectively-bred OP and OR rats, we assessed food-motivated behavior following ad lib access to chow (CH), junk-food (JF), or 10d of JF followed by a return to chow diet (JF-Dep). Behavioral tests included conditioned reinforcement, instrumental responding, and free consumption. Additionally, optogenetic, chemogenetic, and pharmacological approaches were used to examine NAc CP-AMPAR recruitment following diet manipulation and ex vivo treatment of brain slices. Motivation for food was greater in OP than OR rats, as expected. However, JF-Dep only produced enhancements in food-seeking in OP groups, while continuous JF access reduced food-seeking in both OPs and ORs. Reducing excitatory transmission in the NAc was sufficient to recruit CP-AMPARs to synapses in OPs, but not ORs. In OPs, JF-induced increases in CP-AMPARs occurred in mPFC-, but not BLA-to-NAc inputs. Diet differentially affects behavioral and neural plasticity in obesity susceptible populations. We also identify conditions for acute recruitment of NAc CP-AMPARs; these results suggest that synaptic scaling mechanisms contribute to NAc CP-AMPAR recruitment. Overall, this work improves our understanding of how sugary, fatty food consumption interacts with obesity susceptibility to influence food-motivated behavior. It also extends our fundamental understanding of NAc CP-AMPAR recruitment; this has important implications for motivation in the context of obesity as well as drug addiction.

neuroscience↗

bioRxiv2019

Improved demand curve for food or drug consumption in animal experiments

The incorporation of microeconomics concepts into studies using preclinincal self-administration procedures has provided critical insights into the factors that influence consumption of a wide range of food and drug reinforcers. In particular, the fitting of demand curves to consumption data provides a powerful analytic tool for computing objective metrics of behavior that can be compared across a wide range of reward types and experimental settings. The results of these analyses depend crucially on the mathematical form used to fit the data. The most common choice is an exponential form proposed by Hursh and Silberberg, which is widely used and has provided fundamental insights into relationships between cost and consumption, but it also has some disadvantages. In this paper we first briefly review the use of demand curves to quantify the motivating effects of food and drugs, then we describe the current methodology and highlight some potential issues that arise in its application. To address these issues, we propose a new mathematical framework for the analysis of consumption data, including a new functional form for the demand curve. We show that this proposed form gives good fits to data on a range of reinforcers across different animals and different experimental protocols, while allowing for straightforward calculation of key metrics of demand, including preferred consumption level, maximum response, price at maximum response, and price elasticity of demand. We provide software implementing our entire analysis pipeline, including data fits, data visualization, and the calculation of demand metrics.

animal behavior and cognition↗

bioRxiv2019

Eating junk-food has opposite effects on intrinsic excitability of nucleus accumbens core neurons in obesity-susceptible vs. -resistant rats.

The nucleus accumbens (NAc) plays critical roles in motivated behaviors, including food-seeking and feeding. Differences in NAc function contribute to over-eating that drives obesity, but the underlying mechanisms are poorly understood. In addition, there is a fair degree of variation in individual susceptibility vs. resistance to obesity that is due in part to differences in NAc function. For example, using selectively bred obesity-prone and obesity-resistant rats, we have found that excitability of medium spiny neurons within the NAc core is enhanced in obesity-prone vs. resistant populations, prior to any diet manipulation. However, it is unknown whether consumption of sugary, fatty junk-food alters MSN excitability. Here, whole-cell patch clamp recordings were conducted to examine MSN intrinsic excitability in adult male obesity-prone and obesity-resistant rats with and without exposure to a sugary, fatty junk-food diet. We replicated our initial finding that basal excitability is enhanced in obesity-prone vs. obesity-resistant rats and determined that this is due to a lower IA in prone vs. resistant groups. In addition, the junk-food diet had opposite effects on excitability in obesity-prone vs. obesity-resistant rats. Specifically, junk-food enhanced excitability in MSNs of obesity-resistant rats; this was mediated by a reduction in IA. In contrast, junk-food reduced excitability in MSNs from obesity-prone rats; this was mediated by an increase in IKIR. Thus, individual differences in obesity-susceptibility influence both basal excitability and how MSN excitability adapts to junk-food consumption.

neuroscience↗

bioRxiv2018

Knock-in rat lines with Cre recombinase at the dopamine D1 and adenosine 2a receptor loci.

Genetically-modified mice have become standard tools in neuroscience research. Our understanding of the basal ganglia in particular has been greatly assisted by BAC mutants with selective transgene expression in striatal neurons forming the direct or indirect pathways. However, for more sophisticated behavioral tasks and larger intracranial implants, rat models are preferred. Furthermore, BAC lines can show variable expression patterns depending upon genomic insertion site. We therefore used CRISPR/Cas9 to generate two novel knock-in rat lines specifically encoding Cre recombinase immediately after the dopamine D1 receptor (Drd1a) or adenosine 2a receptor (Adora2a) loci. Here we validate these lines using in situ hybridization and viral vector mediated transfection to demonstrate selective, functional Cre expression in the striatal direct and indirect pathways respectively. We used whole-genome sequencing to confirm the lack of off-target effects, and established that both rat lines have normal locomotor activity and learning in simple instrumental and Pavlovian tasks. We expect these new D1-Cre and A2a-Cre rat lines will be widely used to study both normal brain functions and neurological and psychiatric pathophysiology.

neuroscience↗