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Ferrario, C. R.

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

3 recordsLinked to original sources

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

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

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