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The Role of Patterned Stimulation in Inducing Synaptic Plasticity in the Normal and Injured Brain, Michael Friedlander, PhD
October 6, 2016 @ 10:50 am - 11:15 am
Michael Friedlander, PhD, Vice President of Health Sciences and Technology; Executive Director, Virginia Tech Carilion Research Institute; Senior Dean for Research, Virginia Tech Carilion School of Medicine —
The role of patterned stimulation in inducing synaptic plasticity in the normal and injured brain
Michael J. Friedlander, Quentin Fischer and Hodja Kalikulov, Virginia Tech Carilion Research Institute, Roanoke, Virginia, U.S.A.
Recent advances in deep brain stimulation and the use of other stimulation modalities are providing promise for treating a number of neurological and psychiatric disorders. While the immediate effects of such therapeutic interventions are often dramatic throughout the stimulation, less well characterized are the longer term downstream consequence of such protracted periods of axonal and synaptic activation. The space for varying not only the frequency but the temporal pattern of such stimulation paradigms is relatively unexplored in both preclinical animal models and in the human clinical setting. Moreover, as the actual patterns of action potential activity in the intact living brain tend to be irregular and variable between conditions and individuals, it is also of interest to gain a better understanding of how such individualized patterns may impact synaptic function. Thus, we carried out a systematic in vitro single neuron analysis of the synaptic downstream effects of stimulation of afferents in the occipital cortex of rats reared normally as well as those who had been exposed to an impact mild traumatic brain injury under anesthesia two weeks prior. Utilizing single neuron whole cell patch recording and intracellular calcium imaging from layer 2/3 pyramidal neurons with stimulation of layer 4 in the primary visual area of rat occipital cortex, we employed multiple conditioning test frequencies (1 Hz to 100 Hz) and patterns (varying the coefficient of variation of the distribution of inter-stimulus intervals from 0 to 1.0) in control, sham and mTBI animals. We evaluated synaptic plasticity (LTP, LTD) and intracellular calcium levels at 0.1 Hz baseline stimulation for each combination of frequencies and intervals for each of the three groups. Our findings indicate that the plasticity outcomes (LTP, LTD or no change) are sensitive to the pattern of conditioning stimulation as well as frequency in controls and shams. The neurons in the mTBI brains, while sharing many of the same response characteristics of the controls, also have several distinct differences in their plasticity behavior at particular stimulation patterns. The intracellular resting calcium levels are higher in the neurons in the injure brains, perhaps contributing to their differential synaptic plasticity responses. These results may be applicable to designing customized therapeutic applications, using individual subjects’ intrinsic patterns of activity with a variety of brain stimulation technologies for potential treatments to rebalance (selective strengthening or weakening) of a variety of neurological and psychiatric disorders.