electrophysiological recordings in the primary motor cortex. The PD model was established by stereotaxic unilateral injection of 6-hydroxydopamine (6-OHDA) into the right striatum of mice, while the left sham side was used as the reference. At early stage of PD model, a sandwich-structured SERS tag enables highly specific targeted profiling of picomolar-level DA, and a feedforward neural network resolves highly overlapping AA spectra, allowing reliable identification of AA components at physiological micromolar concentrations. In the lesioned substantia nigra, results reveal a rapid decline in DA levels within 6 h after 6-OHDA injection, followed by a marked elevation of glutamate (Glu) at 9 h; while the primary motor cortex at 9 h starts to emerge pathological β-band hypersynchronization and abnormal β-γ phase amplitude coupling. These molecular and circuit-level disturbances clearly precede overt motor asymmetry that becomes evident only at 27 h postlesion. Integrated transcriptomic and qPCR analysis identifies Glu as a central molecular hub linking early neurochemical imbalance to subsequent neural circuit dysfunction. The findings indicate a DA-depletion-triggered and Glu-centered excitotoxic cascade, and also prospect a early therapeutic window during which restoring Glu homeostasis, enhancing metabolic resilience, or mitigating oxidative stress may help prevent subsequent network destabilization. This synergistic SERS-electrophysiology suite enables time-resolved chemical-to-neurophysiological mapping and provides a general framework for investigating molecular-to-circuit transitions in neurodegenerative disorders.
Yin et al. (Wed,) studied this question.