Oscillatory waveform sharpness asymmetry changes in motor thalamus and motor cortex in a rat model of Parkinson's disease.

Parkinson's disease (PD) causes bursty and oscillatory activity in basal ganglia output that is thought to contribute to movement deficits through impact on motor thalamus and motor cortex (MCx). We examined the effect of dopamine loss on motor thalamus and motor cortex activity by recording neuronal and LFP activities in ventroanterior-ventrolateral (VAVL) thalamus and MCx in urethane-anesthetised control and parkinsonian rats. Dopamine lesion decreased the firing rate and increased the bursting of putative pyramidal neurons in layer V, but not layer VI, of the MCx without changing other aspects of firing pattern.

Early decreases in cortical mid-gamma peaks coincide with the onset of motor deficits and precede exaggerated beta build-up in rat models for Parkinson's disease.

Evidence suggests that exaggerated beta range local field potentials (LFP) in basal ganglia-thalamocortical circuits constitute an important biomarker for feedback for deep brain stimulation in Parkinson's disease patients, although the role of this phenomenon in triggering parkinsonian motor symptoms remains unclear. A useful model for probing the causal role of motor circuit LFP synchronization in motor dysfunction is the unilateral dopamine cell-lesioned rat, which shows dramatic motor deficits walking contralaterally to the lesion but can walk steadily ipsilaterally on a circular treadmill. Within hours after 6-OHDA injection, rats show marked deficits in ipsilateral walking with early loss of significant motor cortex (MCx) LFP peaks in the mid-gamma 41-45 Hz range in the lesioned hemisphere; both effects were reversed by dopamine agonist administration.

Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus.

Alterations in the function of the medial prefrontal cortex (mPFC) and its major thalamic source of innervation, the mediodorsal (MD) thalamus, have been hypothesized to contribute to the symptoms of schizophrenia. The NMDAR antagonist ketamine, used to model schizophrenia, elicits a brain state resembling early stage schizophrenia characterized by cognitive deficits and increases in cortical low gamma (40-70 Hz) power. Here we sought to determine how ketamine differentially affects spiking and gamma local field potential (LFP) activity in the rat mPFC and MD thalamus.

Ventral Medial Thalamic Nucleus Promotes Synchronization of Increased High Beta Oscillatory Activity in the Basal Ganglia-Thalamocortical Network of the Hemiparkinsonian Rat.

Unlabelled: Loss of dopamine is associated with increased synchronization and oscillatory activity in the subthalamic nucleus and basal ganglia (BG) output nuclei in both Parkinson's disease (PD) patients and animal models of PD. We have previously observed substantial increases in spectral power in the 25-40 Hz range in LFPs recorded in the substantia nigra pars reticulata (SNpr) and motor cortex (MCx) in the hemiparkinsonian rat during treadmill walking. The current study explores the hypothesis that SNpr output entrains activity in the ventral medial thalamus (VM) in this frequency range after loss of dopamine, which in turn contributes to entrainment of the MCx and BG.

Effects of L-dopa priming on cortical high beta and high gamma oscillatory activity in a rodent model of Parkinson's disease.

Prolonged L-dopa treatment in Parkinson's disease (PD) often leads to the expression of abnormal involuntary movements known as L-dopa-induced dyskinesia. Recently, dramatic 80 Hz oscillatory local field potential (LFP) activity within the primary motor cortex has been linked to dyskinetic symptoms in a rodent model of PD and attributed to stimulation of cortical dopamine D1 receptors. To characterize the relationship between high gamma (70-110 Hz) cortical activity and the development of L-dopa-induced dyskinesia, cortical LFP and spike signals were recorded in hemiparkinsonian rats treated with L-dopa for 7 days, and dyskinesia was quantified using the abnormal involuntary movements (AIMs) scale.

Subthalamic nucleus activity in the awake hemiparkinsonian rat: relationships with motor and cognitive networks.

Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronized STN local field potential (LFP) activity with activity in motor cortex (MCx) and medial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively.

Oscillatory Activity in Basal Ganglia and Motor Cortex in an Awake Behaving Rodent Model of Parkinson's Disease.

Exaggerated beta range (15-30 Hz) oscillatory activity is observed in the basal ganglia of Parkinson's disease (PD) patients during implantation of deep brain stimulation electrodes. This activity has been hypothesized to contribute to motor dysfunction in PD patients. However, it remains unclear how these oscillations develop and how motor circuits become entrained into a state of increased synchronization in this frequency range after loss of dopamine.

Functional correlates of exaggerated oscillatory activity in basal ganglia output in hemiparkinsonian rats.

Exaggerated beta range (13-30Hz) synchronized activity is observed in the basal ganglia of Parkinson's disease (PD) patients during implantation of deep brain stimulation electrodes and is thought to contribute to the motor symptoms of this disorder. To explore the translational potential of similar activity observed in a rat model of PD, local field potentials (LFPs) and spiking activity in basal ganglia output were characterized in rats with unilateral dopamine cell lesion during a range of behaviors. A circular treadmill was used to assess activity during walking; hemiparkinsonian rats could maintain a steady gait when oriented ipsiversive to the lesioned hemisphere, but were less effective at walking when oriented contraversive to lesion.

State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats.

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, 7 d 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.

Thalamocortical inputs show post-critical-period plasticity.

Experience-dependent plasticity in the adult brain has clinical potential for functional rehabilitation following central and peripheral nerve injuries. Here, plasticity induced by unilateral infraorbital (IO) nerve resection in 4-week-old rats was mapped using MRI and synaptic mechanisms were elucidated by slice electrophysiology. Functional MRI demonstrates a cortical potentiation compared to thalamus 2 weeks after IO nerve resection.

Beta frequency synchronization in basal ganglia output during rest and walk in a hemiparkinsonian rat.

Synchronized oscillatory neuronal activity in the beta frequency range has been observed in the basal ganglia of Parkinson's disease patients and hypothesized to be antikinetic. The unilaterally lesioned rat model of Parkinson's disease allows examination of this hypothesis by direct comparison of beta activity in basal ganglia output in non-lesioned and dopamine cell lesioned hemispheres during motor activity. Bilateral substantia nigra pars reticulata (SNpr) recordings of units and local field potentials (LFP) were obtained with EMG activity from the scapularis muscle in control and unilaterally nigrostriatal lesioned rats trained to walk on a rotary treadmill.

Ipsilateral cortical fMRI responses after peripheral nerve damage in rats reflect increased interneuron activity.

In the weeks following unilateral peripheral nerve injury, the deprived primary somatosensory cortex (SI) responds to stimulation of the ipsilateral intact limb as demonstrated by functional magnetic resonance imaging (fMRI) responses. The neuronal basis of these responses was studied by using high-resolution fMRI, in vivo electrophysiological recordings, and juxtacellular neuronal labeling in rats that underwent an excision of the forepaw radial, median, and ulnar nerves. These nerves were exposed but not severed in control rats.

Effects of dopamine D1 and D2 receptor antagonists on laryngeal neurophysiology in the rat.

Hypophonia is an early symptom in Parkinson's disease (PD) that involves an increase in laryngeal muscle activity, interfering with voice production. Our aim was to use an animal model to better understand the role of different dopamine receptor subtypes in the control of laryngeal neurophysiology. First, we evaluated the combined effects of SCH23390-a D(1) receptor antagonist with a D(2) receptor antagonist (eticlopride) on laryngeal neurophysiology, and then tested the separate effects of selective receptor antagonists.

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

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.

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

The pedunculopontine nucleus (PPN) is a new deep brain stimulation (DBS) target for Parkinson's disease (PD), but little is known about PPN firing pattern alterations in PD. The anesthetized rat is a useful model for investigating the effects of dopamine loss on the transmission of oscillatory cortical activity through basal ganglia structures. After dopamine loss, synchronous oscillatory activity emerges in the subthalamic nucleus and substantia nigra pars reticulata in phase with cortical slow oscillations.

Dopamine lesion-induced changes in subthalamic nucleus activity are not associated with alterations in firing rate or pattern in layer V neurons of the anterior cingulate cortex in anesthetized rats.

Dysfunctional activity in the subthalamic nucleus (STN) is thought to underlie movement deficits of patients with Parkinson's disease. Alterations in STN firing patterns are also evident in the anesthetized rat model of Parkinson's disease, where studies show that loss of striatal dopamine and concomitant changes in the indirect pathway are associated with bursty and oscillatory firing patterns in STN output. However, the extent to which alterations in cortical activity contribute to changes in STN activity is unclear.

Varieties of attention-deficit/hyperactivity disorder-related intra-individual variability.

Intra-individual variability in behavior and functioning is ubiquitous among children with attention-deficit/hyperactivity disorder (ADHD), but it has not been systematically examined or integrated within causal models. This article seeks to provide a conceptual, methodologic, and analytic framework as a foundation for future research. We first identify five key research questions and methodologic issues.

MK801 and amantadine exert different effects on subthalamic neuronal activity in a rodent model of Parkinson's disease.

Efforts to develop adjuvant therapies for the treatment of Parkinson's disease (PD) have led to interest in drugs that could mimic the therapeutic effects of lesion or deep brain stimulation of the subthalamic nucleus (STN). Extracellular single unit recordings were conducted to determine whether noncompetitive NMDA receptor blockade, suggested to have potential as an adjuvant treatment in PD, attenuates rate increases and firing pattern changes observed in the STN in a rodent model of PD. Systemic administration of the noncompetitive NMDA antagonist MK801 to rats with unilateral dopamine cell lesions did not significantly alter burstiness or interspike interval coefficient of variation, although mean firing rate decreased by a modest 20% with 50% of neurons showing decreases in rate >15% and spike train power in the 3-8-Hz (theta) range was reduced.

Nigrostriatal lesion and dopamine agonists affect firing patterns of rodent entopeduncular nucleus neurons.

Altered activity of the entopeduncular nucleus, the rodent homologue of the globus pallidus internal segment in primates, is thought to mediate behavioral consequences of midbrain dopamine depletion in rodents. Few studies, however, have examined dopaminergic modulation of spiking activity in this nucleus. This study characterizes changes in entopeduncular neuronal activity after nigrostriatal dopaminergic lesion and the effects of systemic treatment with selective D(1) (SKF 38393) and D(2) (quinpirole) agonists in lesioned rats.

Multisecond periodicities in basal ganglia firing rates correlate with theta bursts in transcortical and hippocampal EEG.

Multisecond oscillations in firing rate with periods in the range of 2-60 s (mean, 20-35 s) are present in 50-90% of spike trains from basal ganglia neurons recorded from locally anesthetized, immobilized rats. To determine whether these periodic oscillations are associated with similar periodicities in cortical activity, transcortical electroencephalographic (EEG) activity was recorded in conjunction with single- or dual-unit neuronal activity in the subthalamic nucleus (STN) or the globus pallidus (GP), and the data were analyzed with spectral and wavelet analyses. Multisecond oscillations in firing rates of 31% of the STN neurons and 46% of the GP neurons with periodicities significantly correlated with bursts of theta (4-7 Hz) activity in transcortical EEG.