The Heldt Lab
Our lab's primary research interest is in the neural mechanisms mediating fear and anxiety in the mammalian brain, with special emphasis focused on GABAergic mechanisms and influences. we utilize molecular biological techniques as well as behavioral testing paradigms.
The role of the amygdala and GABA transmission in fear conditioning:
In the laboratory, we study the circuits underlying fear by using Pavlovian conditioning procedures in which an initially neutral conditioned stimulus (CS), such as a tone, is repeatedly paired with an aversive unconditioned stimulus (US) such as a shock. After a few CS-US pairings, presentation of the CS alone induces physiological and behavioral responses similar to those seen in normal and abnormal states of fear and anxiety. The results of numerous studies have demonstrated that changes in fast glutamatergic transmission within the amygdala play an important role in the formation of emotional memories associated with the acquisition and extinction of conditioned fear. However, there are converging lines of evidence suggesting that changes in gamma-aminobutyric acid (GABA) transmission is also involved in these processes, as highlighted by the fact that patients suffering from anxiety disorders are commonly treated with benzodiazepines (BZs), which mediate their actions via GABAA receptors (GABAARs)...more
Functional role of local GABAA receptor subtypes:
Our understanding of the behavioral and pharmacological function of GABAARs has been greatly advanced by the development and use of mice with altered expression of receptor subtypes. These mice have revealed that the genetic alterations of individual GABAAR subunits results in distinct changes in their phenotypic behavior and response to BZs and/or site-specific ligands. While the use of these transgenic mice has become an increasingly invaluable tool, these strategies produce broad changes in GABAAR function throughout the neuroaxis and do little to identify the effects of such changes in specific brain regions. To overcome this limitation, our lab has been utilizing site-specific, temporally-inducible, knockdown approaches to investigate the role of GABAAR subunits in regionally defined areas of the brain...more