Our laboratory utilizes multi-level analyses toward understanding (i) the effects of stress on brain and behavior, and (ii) the neuronal mechanisms underlying basic associative learning in mammalian brain. These investigations consist of employing lesion, pharmacological, and in vitro and in vivo neurophysiological techniques.
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Neurocognitive Effects of Stress.
Stress is a biologically significant factor that, by altering brain cell properties, can disturb cognitive processes such as learning and memory. Extensive research indicates that the hippocampus is not only crucially involved in memory formation, but is also highly sensitive to stress. Specifically, stress has been shown to impair both hippocampal-dependent memory tasks and long-term potentiation (LTP) in rodents. We discovered that, in contrast to its effect on LTP, stress enhances long-term depression (LTD) in the hippocampus, and these effects on hippocampal plasticity are mediated via N-methyl-D-aspartate (NMDA) receptors. We also found that the amygdala (video) is central to manifesting stress-related behaviors and changes in hippocampal functioning (Fig. 1). Currently, our lab is investigating stress effects on multiple brain-memory systems (spatial, emotive, motor) and hippocampal place cells (video). Recently, we developed a computer vision-based automated figure-8 maze (video) to investigate stress effects on working memory and decision-making processes.
Neuronal Mechanisms Underlying Basic Associate Learning.
To understand how the brain encodes new information, two Pavlovian conditioning tasks are utilized: eyeblink conditioning and fear conditioning in rats.
- Eyeblink conditioning occurs when a discrete conditioned stimulus (CS; e.g., tone) is contingently paired with a discrete unconditioned stimulus (US; e.g., an airpuff or a shock to the eye) with particular temporal relationships between the CS and US. The animal initially exhibits reflexive eyeblink (unconditioned response, UR) only to the US. Over the course of training, the animal develops a conditioned response (CR) to the CS that mimics the UR, precedes the US in onset time, and peaks at about the time of US onset. For this learning, the cerebellum is essentially involved (Fig. 2).
- Fear conditioning occurs when initially neutral CSs (such as tone, context) are paired with an aversive US (such as electric shocks), which reflexively elicit URs. Through rapid CS-US association formation, the CS comes to elicit various fear CRs that are similar to innate fear responses. Our lab utilizes automated measures of freezing and 22 kHz ultrasonic vocalization (USV) calls as indices of fear. The amygdala critically mediates this task (Fig. 3).
Ethobehavioral Studies of Fear and Stress.
Recently, our laboratory began employing a predator-like Robogator (video) (programmable LEGO Mindstorms robot) and a closed economy (video) (self-contained living setting comprised of safe nest and dangerous foraging zones) to investigate rat's foraging behavior in semi-naturalistic, dynamic fear environments. This novel approach might be useful in revealing how fear (and stress) influences risky decision making in humans, in screening drug effects, and in addressing the neuronal basis of the basic approach-avoid conflicts that contribute to human psychopathologies.