""""""""Fear"""""""" is an emotion that can be aroused by a predictive stimulus that warns of impending danger, such as the growl of a predator or the sight of an angry face. But most of the stimuli we encounter in our environment are non-threatening, so how do we discriminate stimuli that predict danger from those that do not? Learning to recognize danger depends upon the amygdala, a cluster of nuclei in the brain's temporal lobe. When the amygdala is damaged, people and animals are impaired at recognizing stimuli that predict danger. Conversely, overactivation of the amygdala can lead to excessive fear of non-threatening stimuli and may contribute to disorders such as phobias, chronic anxiety, depression, and post-traumatic stress. A better understanding of the amygdala's role in fear learning may thus provide the key to improving diagnosis and treatment for mental disorders characterized by symptoms of fear and anxiety. The experiments proposed here will pursue a novel approach to studying the amygdala's role in fear learning by using a new procedure that allows fear memories to be stored by one hemisphere of the amygdala and not the other. A recent study by the investigator has shown that when rats are trained to fear a noise by pairing it with electric shock delivered to one eyelid, learning to fear the noise depends upon the amygdala contralateral but not ipsilateral from the shocked eyelid. This discovery reveals that the amygdala's fear circuitry is functionally lateralized, so that fear memories about stimuli that predict threats to one side of the body can be represented mainly within the amygdala of the opposite brain hemisphere. An integrated program of behavioral, electrophysiological, and immunostaining experiments will exploit this lateralization to investigate the functional architecture of the amygdala's fear circuitry. First, anatomical pathways that convey information about aversive stimuli to the amygdala will be identified. Second, studies will test the hypothesis that fear memories are stored in the amygdala by synaptic changes triggered by convergence of sensory information about neutral and aversive stimuli. Third, studies will determine whether the left and right hemispheres of the amygdala exert opponent control over lateralized defensive behaviors. Findings from these experiments will help to resolve critical questions about the amygdala's role in learning, memory, and emotions, and thereby pave the way for improving future diagnosis and treatment of anxiety disorders. ? ? ?
|Halladay, Lindsay R; Blair, Hugh T (2017) Prefrontal infralimbic cortex mediates competition between excitation and inhibition of body movements during pavlovian fear conditioning. J Neurosci Res 95:853-862|
|Halladay, Lindsay R; Blair, Hugh T (2015) Distinct ensembles of medial prefrontal cortex neurons are activated by threatening stimuli that elicit excitation vs. inhibition of movement. J Neurophysiol 114:793-807|
|Halladay, L R; Blair, H T (2012) The role of mu-opioid receptor signaling in the dorsolateral periaqueductal gray on conditional and unconditional responding to threatening and aversive stimuli. Neuroscience 216:82-93|
|McNally, Gavan P; Johansen, Joshua P; Blair, Hugh T (2011) Placing prediction into the fear circuit. Trends Neurosci 34:283-92|
|Tarpley, J W; Shlifer, I G; Halladay, L R et al. (2010) Conditioned turning behavior: a Pavlovian fear response expressed during the post-encounter period following aversive stimulation. Neuroscience 169:1689-704|
|Johansen, Joshua P; Tarpley, Jason W; LeDoux, Joseph E et al. (2010) Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray. Nat Neurosci 13:979-86|
|Tarpley, J W; Shlifer, I G; Birnbaum, M S et al. (2009) Bilateral phosphorylation of ERK in the lateral and centrolateral amygdala during unilateral storage of fear memories. Neuroscience 164:908-17|