Publications by authors named "Luz M Villamil"

4 Publications

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Deep brain stimulation of midbrain locomotor circuits in the freely moving pig.

Brain Stimul 2021 Feb 27;14(3):467-476. Epub 2021 Feb 27.

Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address:

Background: Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been studied as a therapeutic target in rodent models of stroke, parkinsonism, and spinal cord injury. Clinical DBS trials have targeted the closely related pedunculopontine nucleus in patients with Parkinson's disease as a therapy for gait dysfunction, with mixed reported outcomes. Recent studies suggest that optimizing the MLR target could improve its effectiveness.

Objective: We sought to determine if stereotaxic targeting and DBS in the midbrain of the pig, in a region anatomically similar to that previously identified as the MLR in other species, could initiate and modulate ongoing locomotion, as a step towards generating a large animal neuromodulation model of gait.

Methods: We implanted Medtronic 3389 electrodes into putative MLR structures in Yucatan micropigs to characterize the locomotor effects of acute DBS in this region, using EMG recordings, joint kinematics, and speed measurements on a manual treadmill.

Results: MLR DBS initiated and augmented locomotion in freely moving micropigs. Effective locomotor sites centered around the cuneiform nucleus and stimulation frequency controlled locomotor speed and stepping frequency. Off-target stimulation evoked defensive and aversive behaviors that precluded locomotion in the animals.

Conclusion: Pigs appear to have an MLR and can be used to model neuromodulation of this gait-promoting center. These results indicate that the pig is a useful model to guide future clinical studies for optimizing MLR DBS in cases of gait deficiencies associated with such conditions as Parkinson's disease, spinal cord injury, or stroke.
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http://dx.doi.org/10.1016/j.brs.2021.02.017DOI Listing
February 2021

Population Averaged Stereotaxic T2w MRI Brain Template for the Adult Yucatan Micropig.

Front Neuroanat 2020 13;14:599701. Epub 2020 Nov 13.

Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, United States.

Population averaged brain templates are an essential tool for imaging-based neuroscience research, providing investigators with information about the expected size and morphology of brain structures and the spatial relationships between them, within a demographic cross-section. This allows for a standardized comparison of neuroimaging data between subjects and provides neuroimaging software with a probabilistic framework upon which further processing and analysis can be based. Many different templates have been created to represent specific study populations and made publicly available for human and animal research. An increasingly studied animal model in the neurosciences that still lacks appropriate brain templates is the adult Yucatan micropig. In particular, T2-weighted templates are absent in this species as a whole. To address this need and provide a tool for neuroscientists wishing to pursue neuroimaging research in the adult micropig, we present the construction of population averaged ( = 16) T2-weighted MRI brain template for the adult Yucatan micropig. Additionally, we present initial analysis of T1-weighted ( = 3), and diffusion-weighted ( = 3) images through multimodal registration of these contrasts to our T2 template. The strategies used here may also be generalized to create similar templates for other study populations or species in need of template construction.
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http://dx.doi.org/10.3389/fnana.2020.599701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691581PMC
November 2020

Activation of Brainstem Neurons During Mesencephalic Locomotor Region-Evoked Locomotion in the Cat.

Front Syst Neurosci 2019 14;13:69. Epub 2019 Nov 14.

The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, United States.

The distribution of locomotor-activated neurons in the brainstem of the cat was studied by c- immunohistochemistry in combination with antibody-based cellular phenotyping following electrical stimulation of the mesencephalic locomotor region (MLR) - the anatomical constituents of which remain debated today, primarily between the cuneiform (CnF) and the pedunculopontine tegmental nuclei (PPT). Effective MLR sites were co-extensive with the CnF nucleus. Animals subject to the locomotor task showed abundant labeling in the CnF, parabrachial nuclei of the subcuneiform region, periaqueductal gray, locus ceruleus (LC)/subceruleus (SubC), Kölliker-Fuse, magnocellular and lateral tegmental fields, raphe, and the parapyramidal region. Labeled neurons were more abundant on the side of stimulation. In some animals, -labeled cells were also observed in the ventral tegmental area, medial and intermediate vestibular nuclei, dorsal motor nucleus of the vagus, n. tractus solitarii, and retrofacial nucleus in the ventrolateral medulla. Many neurons in the reticular formation were innervated by serotonergic fibers. Numerous locomotor-activated neurons in the parabrachial nuclei and LC/SubC/Kölliker-Fuse were noradrenergic. Few cholinergic neurons within the PPT stained for . In the medulla, serotonergic neurons within the parapyramidal region and the nucleus raphe magnus were positive for . Control animals, not subject to locomotion, showed few -labeled neurons in these areas. The current study provides positive evidence for a role for the CnF in the initiation of locomotion while providing little evidence for the participation of the PPT. The results also show that MLR-evoked locomotion involves the parallel activation of reticular and monoaminergic neurons in the pons/medulla, and provides the anatomical and functional basis for spinal monoamine release during evoked locomotion. Lastly, the results indicate that vestibular, cardiovascular, and respiratory centers are centrally activated during MLR-evoked locomotion. Altogether, the results show a complex pattern of neuromodulatory influences of brainstem neurons by electrical activation of the MLR.
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http://dx.doi.org/10.3389/fnsys.2019.00069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868058PMC
November 2019

LFP Oscillations in the Mesencephalic Locomotor Region during Voluntary Locomotion.

Front Neural Circuits 2017 19;11:34. Epub 2017 May 19.

Department of Physiology, Spinal Cord Research Centre, University of ManitobaWinnipeg, MB, Canada.

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 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.
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http://dx.doi.org/10.3389/fncir.2017.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437718PMC
February 2018