Nanosecond Electric Pulses in Neuromodulation: A Journey from Isolated Adrenal Chromaffin Cells to Murine Tissue Slices
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Authors
Viola, Ciara Danielle
Issue Date
2025
Type
Dissertation
Language
en_US
Keywords
adrenal , Ca2+ , catecholamine , chromaffin cell , NEP , transgenic
Alternative Title
Abstract
Neuromodulation using nanosecond electric pulses (NEP) represents an emerging frontier in biomedical research, offering unparalleled precision for targeting cellular structures and modulating physiological processes. This dissertation explores the novel application of NEPs in adrenal chromaffin cells (ACC), focusing on transgenic murine models and transitioning from cellular studies to tissue-level investigations. Building upon foundational work in bovine ACC, we have developed innovative methodologies to stimulate and characterize responses in murine systems, advancing both the scientific understanding and technical applications of NEP-evoked responses.In isolated murine ACC, NEPs reliably elicited transient, reproducible responses with high signal-to-noise ratios, demonstrating their capacity to activate chromaffin cells without inducing sustained cellular damage using 5 ns pulses. These experiments revealed the characteristics of transgenic murine ACC activity in comparison to previous bovine ACC discoveries as being similar, reproducible, and reliable, serving as a crucial stepping stone toward more complex biological contexts. Expanding on these findings, we transitioned to functional imaging and stimulation studies in freshly prepared murine adrenal tissue slices. Within this intact tissue architecture, NEPs were shown to directly activate ACC, marking a pivotal advance in demonstrating their efficacy beyond simplified cellular models. These studies highlight the transient nature of NEP-evoked responses, providing insight into the physiological relevance of this approach of which more investigations are still required.
The foundational work presented in this dissertation bridges the gap between in vitro studies and ex vivo applications, emphasizing the translational potential of NEPs for neuromodulatory research. By building on techniques initially developed in bovine ACC studies, this research demonstrates the versatility and adaptability of NEPs as a tool for probing adrenal physiology. Furthermore, these findings establish a robust platform for future studies investigating adrenal medulla-cortex cross-talk, stress response modulation, and the eventual translation of NEP neuromodulation to in vivo models with potential for remote stimulation of ACC. This work underscores the promise of NEPs not only for advancing our understanding of adrenal physiology but also for their broader implications in therapeutic and neuromodulatory applications.