RESEARCH
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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Stress Effects on Brain and Behavior.
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 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. We also developed a computer vision-based automated figure-8 maze to investigate stress effects on working memory and other cognitive 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; usually a tone) is paired with a discrete unconditioned stimulus (US; usually an airpuff or a shock to the eye) with particular temporal relationships between the CS and US. At first, the naïve animal exhibits reflexive eyeblink (unconditioned response, UR) only to the airpuff US. Over the course of training, the animal gradually 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 contingently 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).