Marquette University, Milwaukee WI
Department of Biomedical Sciences
Research & Techniques
The goal of our research is to understand the neural regulation of emotion, or affect, and the control it exerts over adaptive or maladaptive behavior in the case of obesity and drug-seeking.
Several ongoing research projects are investigating the role of aversion-induced changes in neural activity on motivated behavior.
1. Aversive stimuli suppress dopamine signaling and promote behavior.
We have found that aversive stimuli (such as 90 dB white noise) suppress dopamine release. Interestingly, in a negative reinforcement design, animals will press a lever that terminates this aversive response. We use fiber photometry to characterize the dopamine change in response to the aversive stimulus and its relationship to escape behavior.
Fiber photometry approach. (A) Viral particles induce the expression of dLight, which allows for the measurement of real-time dopamine concentration ([DA]) in behaving animals. (B) Data illustrating the [DA] reduction aligned to the onset of white noise (black diamonds) in a negative reinforcement design. Cooler colors in the heatmap (below) indicate low [DA]. Green triangles indicate a successful lever press that terminated the white noise. Line trace (above) depicts time-averaged [DA] across all trials.
2. Aversive stimuli decrease dopamine signaling and promote cocaine intake.
An aversive stimulus can promote drug intake.
We observe that when an aversive stimulus is presented while an animal is self-administering cocaine, the probability of drug intake increases, particularly when the stimulus is present and dopamine concentration is suppressed.
Representative photometry recording during self-administration: white noise presentation (indicated by black diamonds and red box) causes reduction in NAcC (Nucleus Accumbens Core) [DA] and an increase in drug self-administration. Triangles indicate operant response for cocaine infusions (grey: prior to white noise onset; pink: following white noise onset).
3. Chronic stress impairs approach motivation and encoding of cues that elicit approach in the prefrontal cortex.
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Using an autoshaping design, we have found that chronic stress reduces the ability of a cue to cause approach behavior toward a reward-predictive cue.
Correspondingly, we observe a reduction in activity of a neural pathway involved in approach motivation from the prefrontal cortex to the nucleus accumbens.
Chronic stress reduces CS+ ( Conditioned Stimulus) evoked PL-NAcC (Pre-limbic Nucleus Accumbens Core) Activity. Representative fiber photometric monitoring of trial by trial CS+ encoding in PL-NAcC neurons over 7 days of conditioning in a Control and Stress animal. Thirty second traces of calcium signaling (ΔF/F, Normalized Signal) (represented in pseudo-color) are aligned to 175 CS+ trials for representative Control and Stress animals. Reward delivery is indicated by a red triangle.
4. Aversive stimuli change striatal activity.
We have observed that coincident with an aversion-induced reduction in dopamine in the NAc, there is an increase in activity of a subpopulation of NAc neurons.
A simplified model of how aversive stimuli may change nucleus accumbens activity based on selective expression of dopamine receptors, sensitive to changes in [DA] and projection targets.
Ongoing projects are investigating how aversive stimuli differentially affect D1R and D2R-expressing medium spiny neuron activity in the nucleus accumbens to control motivated behavior.
