Understanding the processing of emotion by the brain is essential for the development of affective treatment of emotional disorders. The study of the neural substrates of emotion has been much advanced by the use of fear conditioning (FC) to study how an aversive association is formed with a neutral auditory conditioned stimulus (CS). Studies in the rat have identified the amygdala as essential for this process: CS processing in the lateral nucleus of the amygdala (LA) is modulated by FC, and also by artificial induction of neural plasticity (LTP) by tetanic electrical stimulation of CS pathways to LA. To study the synaptic plasticity underlying FC, I will develop a mouse preparation that permits independent measurement of the synaptic efficacy of the cortical and thalamic CS pathways to LA in the same awake mouse during FC, as well as concurrent measures of behavior and of CS processing. Electrical stimulation will be use to directly and independently manipulate the transmission properties of CS pathways ti assess the effect of synaptic plasticity in NL synapses on CS processing. Further, by using molecular genetic techniques to reversibly modify the molecular response of LA to plasticity-inducing stimulation (FC, LTP induction) in vivo, we will investigation the molecular mechanisms underlying these forms of plasticity. We will study the effects of a constitutively active form of CamKII, and of an inhibitor of PKA, in AL on electrophysiological correlates of FC and LTP. CaMKII and PKA are implicated in LTP and in behavioral measures of FC.
| Rogan, Michael T; Leon, Kam Sam; Perez, David L et al. (2005) Distinct neural signatures for safety and danger in the amygdala and striatum of the mouse. Neuron 46:309-20 |
