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Meeting ID: 921 6873 9019   Passcode: biomedical

Speaker 1: Hammad Khan (K. Jayant / T. Kinzer-Ursem, advisor)

Title: Alpha-synucleinopathy disrupts motor cortical beta oscillations and functional ensemble dynamics

Abstract: Inclusions of aggregated α-synuclein (aSyn), called Lewy bodies (LBs), are pathological hallmarks in patients with dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). These abnormal deposits of aSyn lead to a rapid decline in cognition and motor performance. Despite remarkable advances in our understanding of the spread of aSyn pathology, the key circuit biomarkers and associated mechanisms through which aSyn aggregates perturb neural circuit dynamics remain largely unknown.  In this study, we injected preformed fibrils of aSyn in deep layers of mouse primary motor cortex (M1), based on the hypothesis that aSyn inoculation in this location might cause a propagation effect across the translaminar cortical circuit. Using high-density electrophysiology and high-speed two-photon (2P) Ca²⁺ imaging, we found that aSyn PFF seeding in M1 of awake locomoting mice led to a loss of sparse neural representation and impaired beta-band dynamics during the prodromal phase of DLB progression. Specifically, we observed a characteristic waveform, termed a beta event, and a concomitant increase in beta event amplitude as a function of aSyn pathology. Beta events consist of stochastic bursting of beta-band waveforms lasting 50-100 ms. We discovered an increase in beta event power across cortical layers compared to sham mice injected with aSyn monomer. Strikingly, these changes first occurred within the superficial layers of M1. Phase clustering analysis of neuronal spiking during locomotion showed an increase in spike preference to extracellular beta potentials across aSyn pathology. Analysis of cortical ensemble activity – via 2P-Ca²⁺ – further revealed a marked increase of spatiotemporal population recruitment in superficial cortical layers leading to a progressive loss of sparse representation. These results point to a local microcircuit interaction that disrupts the normal circuit activity of beta-band and neural representations across M1. Taken together, the detection of ensemble disruption coupled with beta events provides a pathophysiological biomarker for synucleinopathy.

Speaker 2: Vidhya Vijayakrishnan Nair (Y. Tong, advisor)

Title: Human CSF Movement Influenced by Vascular Low-Frequency Oscillations and Respiration

Abstract: The flow of Cerebrospinal fluid (CSF) through the pathways within the central nervous system is of high significance for maintaining normal brain health and function. Nevertheless, the exact driving forces behind CSF flow are still poorly understood. Low-frequency hemodynamic oscillations and respiration are two important mechanisms that have been shown to drive CSF in the brain. This study explores their independent and coupled effects on CSF movement using novel functional MRI scans of the neck. The results show that the CSF movement can be assessed from the neck by studying the interactions between the oscillations of blood and CSF from large blood vessels and ventricles, respectively. Furthermore, a cross-frequency interaction between the two separable mechanisms was also revealed. This capability of the CSF system to respond to multiple physiological forces simultaneously would help unveil the pathological mechanisms behind CSF flow-related disorders and facilitate the development of new therapeutic interventions. Moreover, the simple fMRI method employed here could be used to assess these CSF-related disorders.

Evaluation links:

Hammad Khan: https://purdue.ca1.qualtrics.com/jfe/form/SV_7TEqpoFmC1So8cu

Vidhya Vijayakrishnan Nair: https://purdue.ca1.qualtrics.com/jfe/form/SV_5bUJg6ukLwsXsxg