Abstract: The ability of neurons to respond differentially to specific temporal and spatial patterns of stimulation underlies the storage of memory and information in neural circuits. Synaptic plasticity is one mechanism that conveys this ability to neurons. Brain slice plasticity experiments are widely used to investigate the molecular mechanisms underlying synaptic plasticity; however, there are several limitations. First, most experiments use males and exclude females. To address this, we measured LTP experimentally in both males and cycling females and show that the sex hormone estradiol influences synaptic plasticity. Second, most experiments use regular, periodic stimulation patterns; however, neurons exhibit significant variability in vivo during repeated experiences and experience a diversity of inhibitory inputs. To investigate synaptic plasticity in vivo, we created a data-driven, multi-compartmental model of a striatal spiny projection neuron with sophisticated calcium dynamics. Our synaptic plasticity rule, based on amplitude and duration of calcium transients, can correctly predict the direction of synaptic plasticity for both spike-timing and frequency-based stimulation protocols. We demonstrate that a novel and important function of inhibition is to enhance the difference in calcium between stimulated and non‑stimulated spines, i.e., to enhance synaptic specificity. Using in vivo spike train recordings as inputs, we evaluate how the direction and magnitude of synaptic plasticity are controlled by spatial synaptic interactions and trial-to-trial variability. These results will enable derivation of spike based, spatial plasticity rules for large scale networks of simplified neurons.

Biography: Dr. Blackwell received a VMD and PhD in bioengineering at University of Pennsylvania, as part of the prestigious Veterinary Medical Scientist Training Program (VSMTP). Her professional career began at the not-for-profit Environmental Research Institute of Michigan, where she began developing artificial neural networks for pattern recognition, before changing her research focus to investigate mechanisms of long term memory storage in real neurons. In 1996 Dr. Blackwell joined the faculty of George Mason University, then in August of 2023 became professor and chair of the Roy J Carver Department of Biomedical Engineering at the University of Iowa. Dr. Blackwell is a world leader in computational modeling of calcium dynamics and signaling pathways underlying plasticity. She has developed several software tools for large scale dynamical modeling of the signaling pathways underlying memory storage in neurons. She has used this software to create data-driven models of striatal and hippocampal signaling pathways. Dr. Blackwell also uses the experimental technique of brain slice electrophysiology to understand the effect of sex and sex hormones on synaptic plasticity. She has several collaborations with internationally recognized experimentalists to understand the mechanisms underlying learning in the hippocampus and pathological changes in the striatum due to drugs of abuse. Her research has been funded by the National Institutes of Health, Department of Defense, Human Frontiers Science Program, and the National Science Foundation.

~ BME Host: Tamara Kinzer-Ursem ~

ZOOM LINK: https://purdue-edu.zoom.us/j/98557006856?pwd=Y1Y4cXRuSE1HNUNoZm84RlFKblQwQT09

*Students registered for the seminar are expected to attend in-person.