Viral mediated manipulations of beta-adrenergic receptor subtypes modulate fear conditioning.

Memories are formed through changes in synaptic transmission in specific brain circuits. Evidence points to amygdala, and specifically its lateral nucleus (LA), as a key site of synaptic plasticity underlying fear conditioning, a leading model for studyin g neurobiology of emotional memory. In fear conditioning, a neutral event (CS), such as tone, is paired with a noxious event (US), such as electric shock. In auditory fear conditioning, convergence of CS and US in LA is believed to be necessary for condit ioning to occur. However, the degree of synaptic plasticity taking place in amygdala is regulated by neurochemicals, which can strengthen or weaken the memory that is formed. One such modulator is noradrenaline (NA), which is released widely in the brain in situations involving alertness, stress, or emotional arousal. NA exerts its effects on neurons by activating two main groups of adrenergic receptors (ARs), alpha and beta, each including multiple subtypes with discrete functions. Although studies have shown that blockade of betaARs in LA decreases fear conditioning, little is known about the relative contribution of individual betaAR-subtypes. The overall goal of this project is to elucidate contributions of specific betaAR subtypes in LA to fear condi tioning. The specific aims are: (1) does knock down of specific betaAR-subtypes in LA decrease fear conditioning in rats? (2) does over-expression of beta2-adrenergic receptors in LA increase fear conditioning? To address our aims, we employ viral mediate d in vivo RNA-interference and over-expression of target molecules in LA. Since these viral techniques are routinely used in host laboratories of LeDoux and Picciotto, our project will enable grant candidate Wigestrand to master these techniques and subse quently to establish these methods at UiO. Our results should give new insights into the contribution of NA receptors in fear conditioning, and to understanding and treating anxiety disorders such as PTSD.