Research

Our current research interests are in two main areas: (1) understanding individual differences in learned behavior and its implications for attenuating reward and drug related memories and (2) understanding individual differences in attention and impulsivity particularly relevant for Attention Deficit Hyperactive Disorder (ADHD).  Some of our work is done in close collaboration with Drs. Marie Monfils in our department and Rueben Gonzales in the pharmacology department.

1. INDIVIDUAL DIFFERENCES IN LEARNED BEHAVIOR

Our research team recently demonstrated that rats display a simple learned behavior with significant individual variations and that these differences might reflect different ways they process and store learned information. In our lab, rats are typically trained to learn that a light presentation in a conditioning box predicts delivery of food reward. This simple learning process is very important in understanding how environmental cues can gain control over one’s behavior and even contribute to pathological conditions such as drug addiction. Environmental cues become linked with reinforcing effects of drug and later induce a vulnerable state of drug craving and can elicit drug-seeking behaviors. It has been proven very difficult to “break” this established link and attenuate behaviors triggered by the environmental cues.

In our typical paradigm, after repeated pairings of the light with food, rats acquire various conditioned responses. One common conditioned response displayed by all rats is to approach and monitor the place where the food reward is delivered (see Fig 1). This is an adaptive learned behavior that allows immediate access to the food when it is delivered. Curiously, however, some rats display another conditioned response directed toward the light itself by orienting toward or approaching the light (see Fig 2). This behavior is not needed to obtain the reward and even can be costly because access to the food reward can be delayed. This seemingly maladaptive behavior towards a cue has been observed in a number of different species in various settings. Furthermore, there appears to be substantial individual differences in the expression of this cue-directed behavior where some subjects show high levels of the behavior and others do not. Because cue-directed behaviors are thought to reflect the acquired salience of the cue, the individual differences suggest that different animals process the cue information differently over the course of learning. This further suggests some fundamental differences in the brain function of these rats. However, it is not clear how the presumably different nature of learning influences the way this learned information (memory) is stored, retrieved and processed.

Fig 1. Conditioned foodcup approach

Fig 2. Conditioned orienting

 

 

 

 

 

 

 

 

 

 

2. INDIVIDUAL DIFFERENCES IN ATTENTION AND IMPULSIVITY

Even though cue-directed behaviors such as orienting to the light are not needed for the rat to obtain the food reward, they can be persistent and even resistant to attempts to eliminate them. As a consequence, cue-directed behaviors have been proposed to be a form of impulsivity or reduced inhibitory control. Our recent work directly showed this link between cue-directed behavior and impulsivity. The rats that acquired a strong orienting response to the light also exhibited more impulsive and risky choices in other tasks. Specifically, when the rats were required to choose between two levers in which one delivered an immediate but small reward and the other delivered delayed but larger reward, the rats with strong orienting behavior were more likely to be impulsive and choose the small reward rather than wait for the larger reward. However, if they had a choice between small reward with no possibility of getting accompanying foot shock and larger reward with accompanying foot shock, they were willing to risk receiving foot shock in order to get larger reward. Interestingly, the same rats were more distractible during an attentional task that required them to detect a single cue among five possible cues. Other research suggests that heightened activity of the neurotransmitter dopamine might be partly responsible for strong cue-directed behavior. In support of that result, the rats with strong orienting behavior in my lab also show enhanced ultrasonic vocalization response to the dopamine-enhancing drug, amphetamine. Together, the work from my lab suggests that the rats with strong orienting behavior are well suited to serve as an animal model for understanding behavioral symptoms and responses to treatment for disorders associated with attentional and impulsive issues such as ADHD.

Currently, my lab is examining the factors that contribute to this orienting phenotype. One effort is to determine how orienting behavior is expressed in female rats. Sex differences are known to exist in many mental disorders in terms of symptom profile, comorbidity, underlying neuropathology, clinical progression, and treatment response. However, very little is known about what factors drive these differences.  In order to contribute to knowledge about these human sex differences, it will be necessary to document whether an orienting phenotype exists within the female population. So far, the work with female rats is promising, but much more needs to be done. One effort is to examine the role played by estrogen on orienting and related behaviors. More and more studies are showing that female brains are not simply male brains with added estrogen. There is a lot more to be done to understand how female brains process attention, and our research team is very excited to tackle the unknowns.