Caitlin M Vander Weele

Massachusetts Institute of Technology | MIT · Picower Institute for Learning and Memory

While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psy-chostimulant administration have been well studied; however, such changes have never been examined foll...

Dopamine cell firing can encode errors in reward prediction, providing a learning signal to guide future behavior. Yet dopamine is also a key modulator of motivation, invigorating current behavior. Existing theories propose that fast (phasic) dopamine fluctuations support learning, whereas much slower (tonic) dopamine changes are involved in motiva...

The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive....

Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive reward-seeking behavior. GABAergic neurons in the LH have been shown to mediate appetitive and feeding-related behaviors. Here we show that the GABAergic comp...

Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions1,2; however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons3–6, where neural activi...

A brain circuit to control alcohol intake Most people are exposed to alcohol at some point in their lives, but only a small fraction will develop a compulsive drinking disorder. Siciliano et al. first established a behavioral measure to assess how predisposition interacts with experience to produce compulsive drinking in a subset of mice (see the P...

Decades of research suggest that the mesocortical dopamine system exerts powerful control over mPFC physiology and function. Indeed, dopamine signaling in the medial prefrontal cortex (mPFC) is implicated in a vast array of processes, including working memory, stimulus discrimination, stress responses, and emotional and behavioral control. Conseque...

Stress is a risk factor for many neuropsychiatric disorders, and the mesolimbic dopamine (DA) pathway is a crucial node of vulnerability. Despite the high prevalence of stress-related neuropsychiatric disorders in women, preclinical knowledge on the impact of stress on neural circuitry has predominantly been acquired in males. Here, we examine how...

Stress is a risk factor for many neuropsychiatric disorders, and the mesolimbic dopamine (DA) pathway is a crucial node of vulnerability. Despite the high prevalence of stress-related neuropsychiatric disorders in women, preclinical knowledge on the impact of stress on neural circuitry has predominantly been acquired in males. Here, we examine how...

Unlabelled: Dynamic signaling of mesolimbic dopamine (DA) neurons has been implicated in reward learning, drug abuse, and motivation. However, this system is complex because firing patterns of these neurons are heterogeneous; subpopulations receive distinct synaptic inputs, and project to anatomically and functionally distinct downstream targets,...

Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive reward-seeking behavior. GABAergic neurons in the LH have been shown to mediate appetitive and feeding-related behaviors. Here we show that the GABAergic comp...

Many psychiatric illnesses are characterized by deficits in the social domain. For example, there is a high rate of co-morbidity between autism spectrum disorders and anxiety disorders. However, the common neural circuit mechanisms by which social deficits and other psychiatric disease states, such as anxiety, are co-expressed remains unclear. Here...

Though growth hormone (GH) is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsa...

Although fear directs adaptive behavioral responses, how aversive cues recruit motivational neural circuitry is poorly understood. Specifically, while it is known that dopamine (DA) transmission within the nucleus accumbens (NAc) is imperative for mediating appetitive motivated behaviors, its role in aversive behavior is controversial. It has been...

In addition to blocking dopamine (DA) uptake, cocaine also causes an unconditioned increase in DA release. In drug naive rats, this effect is most robust within the nucleus accumbens (NAc) shell. Recent studies have shown that, in rats trained to self-administer cocaine, cocaine may act in the periphery to enhance mesolimbic DA release. Further, th...