PTSD In The Lateral Amygdala

MODELING THE EFFECTS OF PROPRANOLOL ON MEMORY RECONSOLIDATION FOR PTSD IN THE LATERAL AMYGDALA INTRODUCTION Figure 1. Before and After Propranolol is Administered (Borovac, Josip Anđelo, et al., 2020, World Journal of Cardiology) METHODOLOGY Development Adapted model of Principal CA1, CA3, Hodgkin-Huxley neurons (Fig. 2) which were all split in 50:30:20 ratio of: Figure 2. Interconnected Type A: High spike frequency Neural Network Model Type B: Medium spike frequency Type C: Low spike frequency Post Traumatic Stress Disorder (PTSD) Result of experiencing a 1. Beta Receptors Before Propranolol traumatic event. Induces anxiety and stress in is Administered non-threatening environments. Propranolol Beta blocker prescribed to patients with heart problems and high blood pressure. Blocks norepinephrine (NE), a fight or flight neurotransmitter, from binding to beta-adrenergic receptors. (Fig. 1) 2. Beta Receptors After Propranolol is Beta-Adrenergic Receptors Activation inhibits slow Administered afterhyperpolarization (sAHP)period when neuron resets. Allows cells to fire trains of action potentials, enhancing synaptic connectivity- neurons that fire together wire together. Focus To model the combination of propranolol and memory reconsolidation as it has the Propranolol potential to diminish negative emotions linked to memories in Norepinephrine patients with PTSD. , = CA3 Pyramidal Connection Excitatory Connection I Neurons firing, 0mg (0%) Propranolol Figure 4. Average neuron firing rate, 0mg (0%) Propranolol ib of KEY Red = Type A Green = Type B Blue = Type C Grey = Interneurons With Propranolol: Figure 3. nh itio Implementation n Simulated Propranolol Increased conductance of sAHP in model Step by step process: 1. Propranolol inhibits beta receptors 4. Decreases synaptic connectivity 2. Increases activation of sAHP 5. Memories become more 3. Decreases firing rates of neurons vulnerable to manipulation Graphing/Analysis Firing rates of type A, B, & C and neurons graphed with raster plot. Graphed over time to represent each section of Pavlovian conditioning. Pavlovian conditioning is the associative learning through repeated pairing of stimuli and response. RESULTS Control: ck GLU Neuron = Inhibitory ory m Signal ll Huxley Neuron Hippocampus = R e c Me a Feedba GLU Neuron Hodgkin gu Em lati on ot Re sp ion on al se = CA1 Pyramidal = Re Hippocampus Figure 5. Figure 7. Neurons firing, 20mg (25%) Propranolol Neurons firing, 40mg (50%) Propranolol Neurons firing, 60mg (75%) Propranolol Figure 6. Figure 8. Figure 10. Average neuron firing rate, 20mg (25%) Propranolol Average neuron firing rate, 40mg (50%) Propranolol DISCUSSION Conclusions Model demonstrates increase of sAHP and beta receptor inhibition decreases neuron firing rates throughout Pavlovian conditioning. As propranolol dosage increases, the raster plots display a decrease in neuron firing rates. Synaptic connectivity decreases as neurons fire together less frequently. Memories are more vulnerable to being altered as pre-existing connections are weakened. Thus, our model suggests propranolol has the ability to alter fear-inducing memories. Limitations Assumed propranolol only affects the binding of NE and not dopamine Measured NE only, despite epinephrine having similar behavior in memory reconsolidation. Future Expand model to include the Ventromedial Prefrontal Cortex and Hippocampus - parts of the brain heavily involved in fear memories Explore model to further justify the usage of propranolol and increase personalization of medication treatments in PTSD patients Figure 9. Average neuron firing rate, 60mg (75%) Propranolol Figure 11. Neurons firing, 80mg (100%) Propranolol Figure 12. Average neuron firing rate, 80mg (100%) Propranolol