Abstract
Oscillatory rhythms in local field potentials (LFPs) are thought to coherently bind cooperating neuronal ensembles to produce behaviors, including locomotion. LFPs recorded from sites that trigger locomotion have been used as a basis for identification of appropriate targets for deep brain stimulation (DBS) to enhance locomotor recovery in patients with gait disorders. Theta band activity (6–12 Hz) is associated with locomotor activity in locomotion-inducing sites in the hypothalamus and in the hippocampus, but the LFPs that occur in the functionally defined mesencephalic locomotor region (MLR) during locomotion have not been determined. Here we record the oscillatory activity during treadmill locomotion in MLR sites effective for inducing locomotion with electrical stimulation in rats. The results show the presence of oscillatory theta rhythms in the LFPs recorded from the most effective MLR stimulus sites (at threshold ≤60 μA). Theta activity increased at the onset of locomotion, and its power was correlated with the speed of locomotion. In animals with higher thresholds (>60 μA), the correlation between locomotor speed and theta LFP oscillations was less robust. Changes in the gamma band (previously recorded in vitro in the pedunculopontine nucleus (PPN), thought to be a part of the MLR) were relatively small. Controlled locomotion was best achieved at 10–20 Hz frequencies of MLR stimulation. Our results indicate that theta and not delta or gamma band oscillation is a suitable biomarker for identifying the functional MLR sites.
Highlights
Several areas of the brain have been shown to elicit locomotion when stimulated, including areas of the diencephalon and mesencephalon (Grillner et al, 1997; Jordan and Sławinska, 2014; Kiehn, 2016; Takakusaki et al, 2016)
A stimulus applied in the mesencephalic locomotor region (MLR) at a strength just above threshold (28 μA) induced increased attention indicated by an orienting reaction, looking around and forward quadrupedal locomotion commencing around 3.5 s after the onset of the stimulation, leading to regular locomotion
Changes related to locomotor activity were observed in delta and low theta bands, but they did not persist throughout the locomotor trial, and the delta band activity could be observed at rest
Summary
Several areas of the brain have been shown to elicit locomotion when stimulated, including areas of the diencephalon and mesencephalon (Grillner et al, 1997; Jordan and Sławinska, 2014; Kiehn, 2016; Takakusaki et al, 2016). The pedunculopontine nucleus (PPN) is considered a component of the MLR, a suggestion advanced by Garcia-Rill et al (1986, 1987, 2011). They pointed out that the PPN is defined by the presence of cholinergic neurons, and gait defects, especially in PD, have been proposed to be due to pathological changes in the cholinergic neurons in the PPN. Attempts to localize the areas suitable for DBS for improving locomotion by stimulating the MLR area have focused on the PPN, but increasingly it has been recognized that the CnF and associated structures may be more appropriate targets (Mazzone et al, 2005; Stefani et al, 2007; Piallat et al, 2009; Shimamoto et al, 2010; Alam et al, 2011; Hamani et al, 2011; Thevathasan et al, 2012)
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