Using cellular resolution recording techniques, we address fundamental questions concerned with the formation, initiation, and progression of epileptic seizures in the intact brain. Epileptic seizures likely arise through the aberrant interaction of local neural populations whose underlying circuitry is not well understood. Despite >100 years of research, even the most basic aspects of epilepsy have escaped our understanding, and up to 30% of patients remain unresponsive to pharmacotherapy. No clear answer exists as to how an epileptic network forms over time, how individual seizures start or terminate, why seizures remain focal in one case, or spread in another. One reason for this persistent lack of understanding has been the technical difficulty to study densely packed epileptic networks at sufficient temporal and spatial resolution. We combine cutting edge cellular scale chronic in vivo calcium imaging with electrophysiology, optogenetics, and behavioral assessment in various models of chronic epilepsy in mice. The core goal of the group is the identification of basic local circuit elements of chronically seizure producing networks that in the best case are shared across different types of epilepsy. At the therapeutic level, we develop novel light-based, targeted therapeutic interventions in close collaboration with other research groups to contain local epileptic activity in the intact brain.
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Methods
- Realistic in vivo mouse models of chronic focal epilepsy
- Chronic neocortical and hippocampal two-photon imaging in vivo
- Chronic In vivo electrophysiology (LFP)
- In vitro electrophysiology (Patch clamp and LFP, murine and human tissue)
- Targeted photopharmacology
In vivo imaging across cortical layers and in hippocampus
Glass microprism-, or micro-cylinder-assisted multilayer or hippocampal imaging
Two-photon in vivo imaging of seizure microprogression
Local cortical network recruitment patterns during seizure microprogression
Multimodal recordings across anatomical scales
in vivo
Two-photon Ca2+ imaging +
Local field potential recordings + Intracellular nanosharp recordings
Cellular scale in vivo imaging of neural subtypes
green: Pyramidal cells (PYR) magenta: PV interneurons
5 selected publications
- Bando Y, Wenzel M, Yuste R. (2021) Simultaneous two-photon imaging of action potentials and subthreshold inputs in vivo. Nature Communications 12:7229.
- Wenzel M, Leunig A, Han S, Peterka DS, Yuste R. (2021) Prolonged anesthesia alters brain synaptic architecture. Proc. Natl. Acad. Sci. USA, 118 (7) e2023676118.
- Wenzel M, Hamm JP, Peterka DS, Yuste R. (2019) Acute focal seizures start as local synchronizations of neuronal ensembles. J Neurosci 39(43): 8562-8575.
- Wenzel M*, Han S*, Smith EH*, Hoel E, Greger B, House PA, Yuste R. (2019) Reduced repertoire of cortical microstates and neuronal ensembles in medically induced loss of consciousness.Cell Systems 8: 467–474. *equal contribution
- Wenzel M, Hamm JP, Peterka DS, Yuste R. (2017) Reliable and elastic propagation of cortical seizures in vivo. Cell Reports 19: 2681–26.
