Massively scalable 3D electrophysiology and two-photon imaging in freely-moving animals
Interdisciplinary Areas: | Engineering-Medicine, Micro-, Nano-, and Quantum Engineering, Integrated Neuroscience and Engineering |
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Project Description
Revealing the mechanisms that give rise to critical brain functions such as perceptions, actions, and memories requires monitoring the dynamic fluctuating patterns of activity within intact neural circuits at the cellular, circuit, and system levels and relating these patterns to behavioral outcomes1. However, such studies often require that the animal be head-fixed. While this allows for well-controlled stimuli and stable recordings, the animal is under severe restraint, and this configuration precludes an accurate estimate of behavioral effects on circuits and circuit effects on behaviors2. For example, recent studies have demonstrated prominent and widespread movement-related signals in the brain of head-fixed mice, even in primary sensory areas3. Also, eye movements are large and constant in freely moving rodents but are essentially absent under head restraint. However, it is still unknown what role these signals play in sensory processing, and how they impact cortical coding. In recent work, we have unraveled the presence of traveling waves in the cortex – a feature influenced by behavioral state. Notably, we observe that these traveling waves are orchestrated by sparse, yet robust, ensemble patterns – a critical facet of working memory. Importantly, these dynamics go awry under pathological conditions associated with Parkinson’s disease. Pressing questions remain – for example, how are these traveling waves and ensemble patterns ‘pervaded’ by movement signals? How do they reflect learned associations? How is the plasticity of these circuits consolidated during sleep? And how are they impacted by pathological insults? Using cutting-edge innovations in optical engineering and microfabrication, the goal of this project will be to realize a head-mounted two-photon microscope coupled with 3D electrophysiology probes to record from freely-moving animals – including healthy mice and ones inoculated with α-synuclein (αSyn) preformed fibrils. Not only will our study highlight how traveling waves organize L2/3 ensembles and influence memory consolidation, but it will also help unravel how αSyn aggregation and prion-like propagation lead to time-dependent changes in working memory.
Start Date
01/15/2025
Postdoc Qualifications
The ideal candidate will have a PhD in Electrical Engineering, Biomedical Engineering or Biomedical Sciences including Neuroscience or other related fields, and have a strong instrumentation, fabrication, and experimental background. Other relevant interests include experience with biophysics, wet lab experiments, electrophysiology, and two-photon imaging. Adequate training will be given nonetheless. The successful candidate will work in a multi-disciplinary setting and have a deep interest in using electrical and optical methods to dissect neural circuit mechanisms, and be an excellent communicator.
Co-advisors
Krishna Jayant (BME); kjayant@purdue.edu
Jean-Christophe Rochet (MCMP); jrochet@purdue.edu
Bibliography
1. Wallace, D. J.; Kerr, J. N. Nature methods 2019, 16, (1), 9-11.
2. Miller, C. T.; et al., Current Biology 2022, 32, (10), R482-R493.
3. Saleem, A. B.; Ayaz, A.; Jeffery, K. J.; Harris, K. D.; Carandini, M. Nature neuroscience 2013, 16, (12), 1864-1869.