Altered neuronal activity relationships between the pedunculopontine nucleus and motor cortex in a rodent model of Parkinson's disease

Aravamuthan, Bhooma R.; Bergstrom, Debra A.; French, Robin A.; Taylor, Joseph J.; Parr‐Brownlie, Louise C.; Walters, Judith R.

doi:10.1016/j.expneurol.2008.05.023

Cited by 47 publications

(25 citation statements)

References 108 publications

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“…Supporting this view are the current observations showing that over a range of frequencies and in two behavioral states, increases in oscillatory activity in the SNpr of the hemiparkinsonian rat are consistently accompanied by increases in coherence between motor cortex and SNpr LFPs. These observations are consistent with evidence that dopamine cell loss facilitates striatal transmission of corticostriatal input to downstream sites (Tseng et al, 2001;Murer et al, 2002;Mallet et al, 2006;Walters et al, 2007;Aravamuthan et al, 2008). Other results of this study, however, suggest that additional processes may be involved in determining the profile of activity in basal ganglia output after dopamine cell lesion.…”

Section: Discussionsupporting

confidence: 90%

State-Dependent Spike and Local Field Synchronization between Motor Cortex and Substantia Nigra in Hemiparkinsonian Rats

Brazhnik

Cruz²,

Avila³

et al. 2012

Journal of Neuroscience

125

133

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Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of Parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, seven days after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8–25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25–40 Hz band with a peak frequency at 30–35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25–40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity.

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Section: Discussionsupporting

confidence: 90%

State-Dependent Spike and Local Field Synchronization between Motor Cortex and Substantia Nigra in Hemiparkinsonian Rats

Brazhnik

Cruz²,

Avila³

et al. 2012

Journal of Neuroscience

125

133

View full text Add to dashboard Cite

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“…In Parkinson’s disease, the PPN is thought to be underactive due to overwhelming inhibitory input from GPi (Aravamuthan et al 2007, Gomez-Gallego 2007, Zhang et al 2012) and due to neurodegeneration (Jellinger 1988). However, PPN-DBS clinical trials have found inconsistent therapeutic effects in Parkinson’s disease patients (Androulidakis et al 2008, Aravamuthan et al 2008, Jenkinson 2005, Mazzone et al 2005, Plaha and Gill 2005). …”

Section: Discussionmentioning

confidence: 99%

Computational modeling of pedunculopontine nucleus deep brain stimulation

et al. 2013

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Objective Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson’s disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models, and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results The computational models predicted that: 1) the majority of PPN neurons are activated with −3V monopolar cathodic stimulation; 2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; 3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3V); 4) monopolar stimulation in rostral, lateral, or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at −3V); and, 5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS.

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“…However, RTn receives dopaminergic input from A8-A10 mesencephalic groups (Freeman et al, 2001), indicating that dopamine loss might directly affect activity in this nucleus. While dopamine cell lesion alters the phase relationship between pedunculopontine (PPN) nucleus and cortex (Aravamuthan et al, 2008), the phase relationship associated with dopaminergic lesion is not consistent with PPN driving activity in the PFN.…”

Section: Discussionmentioning

confidence: 99%

Parafascicular thalamic nucleus activity in a rat model of Parkinson's disease

Parr‐Brownlie

Poloskey

Bergstrom

et al. 2009

Experimental Neurology

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Parkinson's disease is associated with increased oscillatory firing patterns in basal ganglia output, which are thought to disrupt thalamocortical activity. However, it is unclear how specific thalamic nuclei are affected by these changes in basal ganglia activity. The thalamic parafascicular nucleus (PFN) receives input from basal ganglia output nuclei and directly projects to the subthalamic nucleus (STN), striatum and cortex; thus basal ganglia mediated changes on PFN activity may further impact basal ganglia and cortical functions. To investigate the impact of increased oscillatory activity in basal ganglia output on PFN activity after dopamine cell lesion, PFN single-unit and local field potential activities were recorded in neurologically intact (control) rats and in both non-lesioned and dopamine lesioned hemispheres of unilateral 6-hydroxydopamine lesioned rats anesthetized with urethane. Firing rates were unchanged 1-2 weeks after lesion; however, significantly fewer spontaneously active PFN neurons were evident. Firing pattern assessments after lesion showed a larger proportion of PFN spike trains had 0.3-2.5 Hz oscillatory activity and significantly fewer spike trains exhibited low threshold calcium spike (LTS) bursts. In paired recordings, more PFN-STN spike oscillations were significantly correlated, but as these oscillations were in-phase, results are inconsistent with feedforward control of PFN activity by inhibitory oscillatory basal ganglia output. Furthermore, the decreased incidence of LTS bursts is incompatible with inhibitory basal ganglia output inducing rebound bursting in PFN after dopamine lesion. Together, results show that robust oscillatory activity observed in basal ganglia output nuclei after dopamine cell lesion does not directly drive changes in PFN oscillatory activity.

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Altered neuronal activity relationships between the pedunculopontine nucleus and motor cortex in a rodent model of Parkinson's disease

Cited by 47 publications

References 108 publications

State-Dependent Spike and Local Field Synchronization between Motor Cortex and Substantia Nigra in Hemiparkinsonian Rats

State-Dependent Spike and Local Field Synchronization between Motor Cortex and Substantia Nigra in Hemiparkinsonian Rats

Computational modeling of pedunculopontine nucleus deep brain stimulation

Parafascicular thalamic nucleus activity in a rat model of Parkinson's disease

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