Abstract
The Substantia Nigra pars reticulata (SNr) is a promising target for deep brain stimulation (DBS) to treat the gait and postural disturbances in Parkinson’s disease (PD). Positioning the DBS electrode within the SNr is critical for the development of preclinical models of SNr DBS to investigate underlying mechanisms. However, a complete characterization of intraoperative microelectrode recordings in the SNr to guide DBS electrode placement is lacking. In this study, we recorded extracellular single-unit activity in anesthetized rats at multiple locations in the medial SNr (mSNr), lateral SNr (lSNr), and the Ventral Tegmental Area (VTA). Immunohistochemistry and fluorescently dyed electrodes were used to map neural recordings to neuroanatomy. Neural recordings were analyzed in the time domain (i.e., firing rate, interspike interval (ISI) correlation, ISI variance, regularity, spike amplitude, signal-to-noise ratio, half-width, asymmetry, and latency) and the frequency domain (i.e., spectral power in frequency bands of interest). Spike amplitude decreased and ISI correlation increased in the mSNr versus the lSNr. Spike amplitude, signal-to-noise ratio, and ISI correlation increased in the VTA versus the mSNr. ISI correlation increased in the VTA versus the lSNr. Spectral power in the VTA increased versus: (1) the mSNr in the 20–30 Hz band and (2) the lSNr in the 20–40 Hz band. No significant differences were observed between structures for any other feature analyzed. Our results shed light on the heterogeneity of the SNr and suggest electrophysiological features to promote precise targeting of SNr subregions during stereotaxic surgery.
Highlights
Deep brain stimulation (DBS) is an effective treatment for tremor, rigidity, and bradykinesia in Parkinson’s disease (PD)
Out of 16 tracks, 8 tracks passed through medial SNr (mSNr), 5 tracks passed through the lateral SNr (lSNr), and 4 tracks passed through the Ventral Tegmental Area (VTA) (Figure 3A)
The mSNr dorsal border was approximately 6.4 mm from the cortical surface according to histology compared to 8.0 mm according to the stereotaxic atlas (Paxinos and Watson, 2007)
Summary
Deep brain stimulation (DBS) is an effective treatment for tremor, rigidity, and bradykinesia in Parkinson’s disease (PD). These distal symptoms are reliably treated by DBS and dopaminergic medication, the axial symptoms of gait and postural disturbances continue to worsen 5 years after implant (St George et al, 2010). Studies in rats (McConnell and Grill, 2013), cats (Takakusaki et al, 2003), and humans (Scholten et al, 2017) suggest that stimulation at lateral SNr (lSNr) sites is less effective at treating the gait disturbances of PD compared to stimulation at medial SNr (mSNr) sites
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