Research areas

Behavior: Extinction of conditioning of fear

Rats were given auditory fear conditioning:

a. habituation trials (tone alone)

b. learn to fear- Conditioning trials (tone paired with foot shock) 

c. learn to not fear- Extinction trials (tone alone) 

d. what percentage of extinction was learn- Test (tone alone) 

 

 Lesions, Intracranial Microinfusion, Brain Stimulation

We have used electrolytic lesions to show that the medial prefrontal cortex (mPFC) is necessary for long-term memory (but not short-term memory) of extinction.  Local infusion of different compounds (e.g. APV, anisomycin, muscimol) into the mPFC were tested the hypothesis that mPFC plays a critical role in extinction.  Electrical stimulation of the mPFC (infralimbic nucleus) modeled on actual neuronal responses (see below) simulates extinction memory.

 

 

 

 Single-Unit Recording from Behaving Rats

One of the best ways to study information processing in the brain is to record the activity of single neurons  during learning.  We use multi-channel recording and computer spike-sorting (DataWave, Plexon) to monitor activity in the mPFC and amygdala during extinction learning.  We have observed that infralimbic neurons signal the tones only after extinction learning when rats are recalling extinction memory.  Stimulation of mPFC produces extinction behavior in rats that never received extinction training, and strengthens extinction memory.  We are planning to combine unit recording with lesion or local inactivation techniques to further probe interactions between different brain structures.

 

 

Genetic and Molecular Approaches

We have observed that long-term memory for extinction depends on NMDA receptors and protein synthesis.  This suggests that extinction training may activate genes.  In collaboration with Dr. Sandra Peņa de Ortiz at the University of Puerto Rico, we are studying gene activation during extinction of conditioned fear.  We are using immunocytochemistry, western blots and cDNA microarrays.  We have observed that extinction activates immediate early genes, which control subsequent gene transcription.