Brain-wide Single-unit Activity During Spike-wave Discharges
Abstract number :
2.173
Submission category :
3. Neurophysiology / 3F. Animal Studies
Year :
2024
Submission ID :
28
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Elzbieta Dulko, MS – University of Virginia
Anna Grace Carns, BS – University of Virginia
Scott Kilianski, PhD – University of Virginia
Isabelle Lesmana, BS – University of Virginia
Magdalena Pikus, BS – University of Virginia
Mark Beenhakker, PhD – University of Virginia
Rationale: The spike-wave discharge (SWD) is the hallmark of Absence Epilepsy (AE), a disease that affects up to 8 per 100,000 children under 15 years of age. Currently available anti-seizure medications reduce seizure occurrence but are associated with unacceptable freedom from treatment failure rates (~50%) due to intolerable side effects. Understanding the neuronal mechanisms of SWD generation is a necessary step for developing better, targeted treatments. Prior research suggested that SWDs are driven by hypersynchronous neural circuits of the cortex and thalamus. However, beyond this general conclusion, many significant questions remain, and little is known about neuronal activity underlying seizure generation.
Methods: 24 C3H/HeJ (“Gria4”) mice, a common model of spontaneous SWDs were used in this study. Using simultaneous single-unit and electrocorticographic (ECoG) recordings in awake head-fixed mice, we examined firing of ~1,000 individual neurons across 20 brain structures including somatosensory cortex, most thalamic nuclei, and hippocampus.
Results:
We found that most brain structures are recruited during the SWD and fire sparsely but synchronously during each cycle of the SWD. Moreover, phase-analysis revealed that temporal firing pattern is modulated by SWD and consistent between mice. We also found that within and between brain structures synchrony increase 3.5-fold and 2-fold compared to the baseline, respectively during SWDs. We resolved the time lag between brain structures and identified the leading and following brain structures.
Conclusions: The results of this study – a single-unit resolution activity map driving during the SWD - is an essential first step for the development of novel therapeutic strategies for a common childhood form of epilepsy associated with unacceptable failure rates.
Funding: This project received support from NIH (R01NS126594 to MB), UVA Wagner Fellowship (to ED), UVA Double Hoo Research Grant (to ED and AGC), and Ingrassia Family Echols Scholars Research Grant (to AGC).
Neurophysiology