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James Porter, PhD

Associate Professor

Department of Physiology, Pharmacology and Toxicology

1. Cellular Mechanisms that encode extinction of learned fear

   This project is part of a collaboration with Dr. Gregory Quirk at UPR Medical School in San Juan. Fear extinction is the decrease in fear responses that normally occurs when a conditioned stimulus like a tone is repeatedly presented in the absence of the unconditioned stimulus such as a shock. Rather than erase fear memory, extinction is thought to form a new memory that signals safety. The goal of this project is to understand how extinction memory is encoded at the level of single neurons. Since a growing body of literature implicates enhanced activity in the infralimbic region (IL) of the medial prefrontal cortex in the retention of fear extinction, we are examining the intrinsic cellular mechanisms that mediate the enhanced activity of the IL neurons after extinction training. We are applying a multidisciplinary approach combining in vitro patch-clamp electrophysiology, histology, in vivo single neuron recordings, behavioral training, and in vitro and in vivo neuropharmacology. Because extinction-based exposure therapies are the main treatment for post-traumatic stress disorder and phobias, understanding the cellular mechanisms of extinction will likely lead to new strategies to treat these disorders.
   
   
           
    

2. Modulation of extinction memory by manipulating the excitability of IL neurons
   
   To determine whether the retention of extinction memory can be modulated by manipulating the excitability of IL neurons, we are identifying receptors that control intrinsic excitability in IL neurons. We are examining the effects of agonists of beta adrenergic receptors and metabotropic glutamate receptors subtype 5 (mGluR5) on the intrinsic excitability of IL neurons in brain slices. We are also determining whether antagonists of these receptors disrupt extinction memory. Finally, we will be determining whether the stimulation of mGluR5 receptors in vivo can augment the recall of extinction training and increase the bursting activity of IL neurons in vivo.
    
3. Cellular Mechanisms that Modulate Thalamocortical Circuits
   
   We are studying how thalamic excitation of the cortex is inhibited by presynaptic adenosine, GABAB, and group II metabotropic glutamate receptors in brain slices with intact thalamocortical circuitry. Understanding how the activation of these cortical circuits is regulated will provide important insights into how sensory processing can be altered pharmacologically. Perhaps in the future one would have the ability to alter sensory processing via receptor agonists or antagonists in order to assist in new skill learning, relearning after an accident or stroke, or prevent aberrant cortical reorganization such as occurs in phantom limb pain.
   
   
   
    
4. BDNF-modulation of Mossy fiber synaptic plasticity and Fear Extinction
   
   In collaboration with Dr. Kenira Thompson at PSM, we are initially planning to determine whether brain derived neurotrophic factor (BDNF) enhances mossy fiber long-term plasticity in hippocampal brain slices. In future experiments, we will attempt to enhance extinction memory by infusing BDNF directly into the hippocampus.
   
   
   
   
    
5. Effects of HIV proteins on Neuronal Circuitry
   
   In collaboration with Dr. Richard Noel at PSM, we are planning on examining the effects of HIV-encoded proteins on neuronal circuitry in cultured hippocampal slices. Our hypothesis is that HIV proteins will decrease synaptic connections between neurons and inhibit the induction of synaptic plasticity.