Wideband ratiometric measurement of tonic and phasic dopamine release in the striatum.

Reward learning, cognition, and motivation are supported by changes in neurotransmitter levels across multiple timescales. Current measurement technologies for various neuromodulators (such as dopamine and serotonin) do not bridge timescales of fluctuations, limiting the ability to define the behavioral significance, regulation, and relationship between fast (phasic) and slow (tonic) dynamics. To help resolve longstanding debates about the behavioral significance of dopamine across timescales, we developed a novel quantification strategy, augmenting extensively used carbon-fiber Fast Scan Cyclic Voltammetry (FSCV).

Corticotropin releasing factor alters the functional diversity of accumbal cholinergic interneurons.

Cholinergic interneurons (ChIs) provide the main source of acetylcholine in the striatum and have emerged as a critical modulator of behavioral flexibility, motivation, and associative learning. In the dorsal striatum (DS), ChIs display heterogeneous firing patterns. Here, we investigated the spontaneous firing patterns of ChIs in the nucleus accumbens (NAc) shell, a region of the ventral striatum.

Corticotropin releasing factor alters the functional diversity of accumbal cholinergic interneurons.

Cholinergic interneurons (ChIs) provide the main source of acetylcholine in the striatum and have emerged as a critical modulator of behavioral flexibility, motivation, and associative learning. In the dorsal striatum, ChIs display heterogeneous firing patterns. Here, we investigated the spontaneous firing patterns of ChIs in the nucleus accumbens (NAc) shell, a region of the ventral striatum.

Transient effects of junk food on NAc core MSN excitability and glutamatergic transmission in obesity-prone female rats.

Objective: The nucleus accumbens (NAc) plays critical roles in eating and food seeking in rodents and humans. Diets high in fats and sugars ("junk food") produce persistent increases in NAc function in male obesity-prone rats. This study examines effects of junk food and junk food deprivation on NAc core medium spiny neuron (MSN) excitability and glutamate transmission in females.

Ranking the contribution of behavioral measures comprising oxycodone self-administration to reinstatement of drug-seeking in male and female rats.

Introduction: Rates of relapse to drug use during abstinence are among the highest for opioid use disorder (OUD). In preclinical studies, reinstatement to drug-seeking has been extensively studied as a model of relapse-but the work has been primarily in males. We asked whether biological sex contributes to behaviors comprising self-administration of the prescription opioid oxycodone in rats, and we calculated the relative contribution of these behavioral measures to reinstatement in male and female rats.

Neural Mechanisms Mediating Sex Differences in Motivation for Reward: Cognitive Bias, Food, Gambling, and Drugs of Abuse.

Sex differences in motivation for food rewards, gambling, and drugs of abuse are modulated by multiple factors, including sensory stimuli, gonadal hormones, and cognitive bias. Cues, drugs of abuse, and a high-fat diet can significantly impact neural signaling in the reward system and functioning of neural systems that regulate executive functions differentially in males and females. Additionally, sex differences in risky decision-making, cognitive bias, and motivation for food and drugs of abuse are mediated by gonadal hormones in both sexes.

Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring.

The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. A number of social and cognitive abnormalities have been documented in these children as they reach young adulthood. However, little is known about the mechanisms underlying developmental effects of prenatal opioid exposure.

Insulin Bidirectionally Alters NAc Glutamatergic Transmission: Interactions between Insulin Receptor Activation, Endogenous Opioids, and Glutamate Release.

Human fMRI studies show that insulin influences brain activity in regions that mediate reward and motivation, including the nucleus accumbens (NAc). Insulin receptors are expressed by NAc medium spiny neurons (MSNs), and studies of cultured cortical and hippocampal neurons suggest that insulin influences excitatory transmission via presynaptic and postsynaptic mechanisms. However, nothing is known about how insulin influences excitatory transmission in the NAc.

The neurobiology of abstinence-induced reward-seeking in males and females.

Drugs of abuse and highly palatable foods (e.g. high fat or sweet foods) have powerful reinforcing effects, which can lead to compulsive and addictive drives to ingest these substances to the point of psychopathology and self-harm--specifically the development of Substance Use Disorder (SUD) and obesity.

Sex specific effects of "junk-food" diet on calcium permeable AMPA receptors and silent synapses in the nucleus accumbens core.

CP-AMPARs in the nucleus accumbens (NAc) mediate cue-triggered motivation for food and cocaine. In addition, increases in NAc CP-AMPAR expression and function can be induced by cocaine or sugary, fatty junk-foods. However, the precise nature of these alterations and the degree to which they rely on the same underlying mechanisms is not well understood.

Effects of the estrous cycle and ovarian hormones on cue-triggered motivation and intrinsic excitability of medium spiny neurons in the Nucleus Accumbens core of female rats.

Naturally occurring alterations in estradiol influence food intake in females. However, how motivational responses to food cues are affected by the estrous cycle or ovarian hormones is unknown. In addition, while individual susceptibility to obesity is accompanied by enhanced incentive motivational responses to food cues and increased NAc intrinsic excitability in males, studies in females are absent.

Functional and structural plasticity contributing to obesity: roles for sex, diet, and individual susceptibility.

The role of cortico-striatal pathways in cue-triggered motivational processes have been extensively studied. However, recent work has begun to examine the potential contribution of plasticity in these circuits to obesity. Despite the inclusion of women in human obesity studies examining neurobehavioral alterations in cue-triggered motivation, preclinical studies have focused mainly on male subjects.