Fear conditioning has emerged as an important model system for studying the mechanisms of associative memory formation and has direct relevance to human fear related psychiatric disorders. A great deal of research implicates the lateral nucleus of the amygdala as a key storage site for fear memories. More recent evidence, however, suggests that other brain areas in the fear circuit such as the Central Nucleus of the Amygdala (CeA) also undergo plastic changes during fear learning. The mechanisms governing these changes have yet to be elucidated and the impact that this plasticity has on neural processing within these regions remains unclear. The goal of this proposal is to begin to address these important questions using a combination of techniques from slice electrophysiology and spatially restricted viral vector expression of transgenes to in-vivo single unit recording and behavior. The proposed experiments will examine how information processing is altered in CeA neurons during fear learning by recording from single neurons in the awake behaving animal during fear learning. In parallel studies I will also test whether fear conditioning is accompanied by plastic changes in excitatory and/or inhibitory synaptic transmission in CeA neurons. If fear conditioning is accompanied by plasticity of excitatory synapses, we will then test whether AMPA receptor insertion, a potential mechanism for these changes, is required for the acquisition of fear learning. Using this approach it will be possible to examine the mechanisms by which fear memories are encoded in CeA neurons at the synaptic and single neuron levels and finally whether these changes are important for behavioral learning.
Fear conditioning closely models human fear related psychiatric conditions such as post-traumatic stress and panic disorders and has given us a window into how the brain is altered under conditions of extreme duress. By offering a richer understanding of the changes that occur in the brain during fear learning, the proposed studies may have important implications for our understanding of the neural processes mediating pathological disorders and their eventual treatment. ? ? ?
| Johansen, Joshua P; Diaz-Mataix, Lorenzo; Hamanaka, Hiroki et al. (2014) Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation. Proc Natl Acad Sci U S A 111:E5584-92 |
| Johansen, Joshua P; Wolff, Steffen B E; Luthi, Andreas et al. (2012) Controlling the elements: an optogenetic approach to understanding the neural circuits of fear. Biol Psychiatry 71:1053-60 |
| Johansen, Joshua P; Hamanaka, Hiroki; Monfils, Marie H et al. (2010) Optical activation of lateral amygdala pyramidal cells instructs associative fear learning. Proc Natl Acad Sci U S A 107:12692-7 |
