Biology subjects

Gnazzo, F.

Publications and source records attributed to Gnazzo, F..

3 recordsLinked to original sources

bioRxiv2025

Striatal signaling tracks naturalistic short-term fluctuations in hunger-satiety

The neuromodulator dopamine is integral to feeding behavior, believed to modulate food pursuit and satiety. Here, we examine how dopamine signaling in the nucleus accumbens changes during consumption as animals transition from hunger to satiety in naturalistic feeding. Dopamine transiently increases during food approach; however, the magnitude of this approach-related increase diminishes across progressive pellet ingestion, reflecting short-term satiation. These approach-related dopamine transients recover during intermeal intervals. Fasting dissociates the regulation of meal size and frequency, reflecting termination and initiation, respectively, with observable differences in dopamine corresponding to changes in meal size but not frequency. Despite substantially decreasing feeding, pharmacological satiation via a glucagon-like peptide-1 (GLP-1) agonist had no impact on average dopamine transients on food approach but abolished the short-term fluctuations related to on-going eating, suggesting that the GLP-1 agonist disengaged or decoupled dopamine from its modulatory role in meal patterning.

neuroscience↗

bioRxiv2025

Accumbal Dopamine and Acetylcholine Dynamics during Psychostimulant Sensitization

Behavioral sensitization to repeated psychostimulant exposure is believed to contribute to the development of addiction. Nucleus accumbens (NAcc) dopamine (DA) is known to be a key substrate in sensitization, though recent work suggests that striatal acetylcholine (ACh) may also play a critical role. However, underlying ACh changes and their relationship to DA signaling have not been characterized. Here, we used dual-color fiber photometry to simultaneously measure DA and ACh in the NAcc shell of mice across repeated injections of cocaine or amphetamine. Repeated exposure progressively elevated locomotor activity and increased slow extracellular DA while attenuating transient DA release. Psychostimulants reduced phasic ACh transient amplitude and frequency, an effect that sensitized with repeated injections. However, the temporal coupling of DA and ACh remained unchanged. To determine whether D2 receptors (D2Rs) on cholinergic interneurons (CINs) drive this effect, we generated CIN-selective D2R knockout (KO) mice. Surprisingly, KOs continued to show an acute decrease in ACh and intact DA-ACh correlations after psychostimulant administration. However, they failed to exhibit sensitization of either DA or ACh in response to repeated psychostimulant administration. Despite this lack of sensitization in underlying neuromodulator signaling, the KO mice nevertheless exhibited behavioral sensitization, though at a slower rate than wild-type. These findings suggest that neural sensitization to psychostimulants is dependent on D2R expressed on CINs, but that behavioral sensitization is not dependent on sensitization of these underlying signals.

neuroscience↗

bioRxiv2024

DIETARY REGULATION OF SILENT SYNAPSES IN THE DORSOLATERAL STRIATUM

Obesity and drugs of abuse share overlapping neural circuits and behaviors. Silent synapses are transient synapses that are important for remodeling brain circuits. They are prevalent during early development but largely disappear by adulthood. Drugs of abuse increase silent synapses during adulthood and may facilitate reorganizing brain circuits around drug-related experience, facilitating addiction and contributing to relapse during treatment and abstinence. Whether obesity causes alterations in the expression of silent synapses in a manner similar to drugs of abuse has not been examined. Using a dietary-induced obesity paradigm, mice that chronically consumed high fat diet (HFD) exhibited increased silent synapses in both direct and indirect pathway medium spiny neurons in the dorsolateral striatum. Both the time of onset of increased silent synapses and their normalization upon discontinuation of HFD occurs on an extended time scale compared to drugs of abuse. These data demonstrate that chronic consumption of HFD, like drugs of abuse, can alter mechanisms of circuit plasticity likely facilitating neural reorganization analogous to drugs of abuse.

neuroscience↗