Winston-Salem, NC, United States
Winston-Salem, NC, United States

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Zhang Y.,Peking University | Wang N.,CAS Institute of Psychology | Wang J.-Y.,CAS Institute of Psychology | Chang J.-Y.,Neuroscience Research Institute of North Carolina | And 3 more authors.
Molecular Pain | Year: 2011

Background: The ability to encode noxious stimulus intensity is essential for the neural processing of pain perception. It is well accepted that the intensity information is transmitted within both sensory and affective pathways. However, it remains unclear what the encoding patterns are in the thalamocortical brain regions, and whether the dual pain systems share similar responsibility in intensity coding.Results: Multichannel single-unit recordings were used to investigate the activity of individual neurons and neuronal ensembles in the rat brain following the application of noxious laser stimuli of increasing intensity to the hindpaw. Four brain regions were monitored, including two within the lateral sensory pain pathway, namely, the ventral posterior lateral thalamic nuclei and the primary somatosensory cortex, and two in the medial pathway, namely, the medial dorsal thalamic nuclei and the anterior cingulate cortex. Neuron number, firing rate, and ensemble spike count codings were examined in this study. Our results showed that the noxious laser stimulation evoked double-peak responses in all recorded brain regions. Significant correlations were found between the laser intensity and the number of responsive neurons, the firing rates, as well as the mass spike counts (MSCs). MSC coding was generally more efficient than the other two methods. Moreover, the coding capacities of neurons in the two pathways were comparable.Conclusion: This study demonstrated the collective contribution of medial and lateral pathway neurons to the noxious intensity coding. Additionally, we provide evidence that ensemble spike count may be the most reliable method for coding pain intensity in the brain. © 2011 Zhang et al; licensee BioMed Central Ltd.


PubMed | Guangdong Pharmaceutical University, Southern Medical University and Neuroscience Research Institute of North Carolina
Type: | Journal: Neuroscience letters | Year: 2015

The pedunculopontine nucleus (PPN) is connected to spinal, cerebellar and cerebral motor control structures and can be activated with external electrodes. Intrinsic cholinergic neuronal degeneration in the PPN is associated with postural instabilities and gait disturbances (PIGD) in advanced Parkinsons disease (PD). Clinical studies have demonstrated that PPN stimulation may improve PIGD. We investigated this claim and the underlying mechanisms using the 6-hydroxydopamine (6-OHDA) hemilesion model of PD. In this study, gait-related parameters, including the base of support (BOS), stride length, and maximum contact area, were analyzed via CatWalk gait analysis following PPN-low frequency stimulation (LFS) of rats with unilateral 6-OHDA lesions. Additionally, neurotransmitter concentrations in the ventrolateral thalamic nucleus (VL) were measured by microdialysis and liquid chromatography-mass spectrometry (LC-MS). Our data revealed that unilateral 6-OHDA lesions of the medial forebrain bundle (MFB) induced significant gait deficits. PPN-LFS significantly improved the BOS (hindlimb) and maximum contact area (impaired forelimb) scores, whereas no other gait parameters were significantly affected. Unilateral 6-OHDA MFB lesions significantly decreased acetylcholine (ACh) and moderately decreased noradrenaline (NA) concentrations in the VL. PPN-LFS mildly reversed the ACh loss in the VL in the lesioned rats but did not alter the NA levels. Taken together, our data indicate that PPN-LFS is useful for treating gait deficits of PD and that these effects are probably mediated by a rebalancing of ACh levels in the PPN-VL pathway. Thus, our findings provide possible insight into the mechanisms underlying PIGD in PD.


Pan Q.,Southern Medical University | Zhang W.,Southern Medical University | Wang J.,CAS Institute of Psychology | Luo F.,CAS Institute of Psychology | And 3 more authors.
Journal of Korean Neurosurgical Society | Year: 2015

Objective : The aim of this study was to investigate voluntary wheel running behavior in the unilateral 6-hydroxydopamine (6-OHDA) rat model. Methods : Male Sprague-Dawley rats were assigned to 2 groups: 6-OHDA group (n=17) and control group (n=8). The unilateral 6-OHDA rat model was induced by injection of 6-OHDA into unilateral medial forebrain bundle using a stereotaxic instrument. Voluntary wheel running activity was assessed per day in successfully lesioned rats (n=10) and control rats. Each behavioral test lasted an hour. The following parameters were investigated during behavioral tests: the number of running bouts, the distance moved in the wheel, average peak speed in running bouts and average duration from the running start to the peak speed. Results: The number of running bouts and the distance moved in the wheel were significantly decreased in successfully lesioned rats compared with control rats. In addition, average peak speed in running bouts was decreased, and average duration from the running start to the peak speed was increased in lesioned animals, which might indicate motor deficits in these rats. These behavioral changes were still observed 42 days after lesion. Conclusion: Voluntary wheel running behavior is impaired in the unilateral 6-OHDA rat model and may represent a useful tool to quantify motor deficits in this model. © 2015 The Korean Neurosurgical Society. All right reserved.


Azarov A.V.,Neuroscience Research Institute of North Carolina | Woodward D.J.,Neuroscience Research Institute of North Carolina
Physiology and Behavior | Year: 2014

Alcohol-preferring (P) rats develop high ethanol intake over several weeks of water/10% ethanol (10E) choice drinking. However, it is not yet clear precisely what components of drinking behavior undergo modification to achieve higher intake. Our concurrent report compared precisely measured daily intake in P vs. non-selected Wistar and Sprague Dawley (SD) rats. Here we analyze their drinking patterns and bouts to clarify microbehavioral components that are common to rats of different genetic backgrounds, vs. features that are unique to each. Under sole-fluid conditions P, Wistar and SD rats all consumed water at a high initial rate followed by a slow maintenance phase, but 10E - in a distinctly different step-like pattern of evenly distributed bouts. During choice period, 10E vs. water patterns for P rat appeared as an overlap of sole-fluid patterns. The SD rat choice patterns resembled sole-fluid patterns but were less regular. Choice patterns in Wistar differed from both P and SD rats, by consisting of intermixed small frequent episodes of drinking both 10E and water. Wistar and SD rats increased choice ethanol intake by elevating the number of bouts. A key finding was that P rat increased choice ethanol intake through a gradual increase of the bout size and duration, but kept bout number constant. This supports the hypothesis that genetic selection modifies microbehavioral machinery controlling drinking bout initiation, duration, and other pattern features. Precision analysis of drinking patterns and bouts allows differentiation between genetic lines, and provides a venue for study of localized circuit and transmitter influences mediating mesolimbic control over ethanol consumption. © 2013.


Azarov A.V.,Neuroscience Research Institute of North Carolina | Woodward D.J.,Neuroscience Research Institute of North Carolina
Physiology and Behavior | Year: 2014

The goal of this study was to clarify similar and distinctly different parameters of fluid intake during early phases of ethanol and water choice drinking in alcohol preferring P-rat vs. non-selected Wistar and Sprague Dawley (SD) rats. Precision information on the drinking amounts and timing is needed to analyze micro-behavioral components of the acquisition of ethanol intake and to enable a search for its causal activity patterns within individual CNS circuits. The experiment followed the standard ethanol-drinking test used in P-rat selective breeding, with access to water, then 10% ethanol (10E) as sole fluids, and next to ethanol/water choice. The novelty of the present approach was to eliminate confounding prandial elevations of fluid intake, by time-separating daily food from fluid access. P-rat higher initial intakes of water and 10E as sole fluids suggest adaptations to ethanol-induced dehydration in P vs. Wistar and SD rats. P-rat starting and overall ethanol intake during the choice period were the highest. The absolute extent of ethanol intake elevation during choice period was greatest in Wistar and their final intake levels approached those of P-rat, contrary to the hypothesis that selection would produce the strongest elevation of ethanol intake. The total daily fluid during ethanol/water choice period was strikingly similar between P, Wistar and SD rats. This supports the hypothesis for a universal system that gauges the overall intake volume by titrating and integrating ethanol and water drinking fluctuations, and indicates a stable daily level of total fluid as a main regulated parameter of fluid intake across the three lines in choice conditions. The present findings indicate that a stable daily level of total fluid comprises an independent physiological limit for daily ethanol intake. Ethanol drinking, in turn, stays under the ceiling of this limit, driven by a parallel mechanism of ethanol/water choice. © 2013.


Zhou M.,Southern Medical University | Zhang W.,Southern Medical University | Chang J.,Neuroscience Research Institute of North Carolina | Wang J.,Southern Medical University | And 5 more authors.
Neuroscience Letters | Year: 2015

Gait deficits are important clinical symptoms of Parkinson's disease (PD) but are rarely studied. In this study we made three different rat PD models by administration of 6-hydroxydopamine into caudate putamen (CPU), medial forebrain bundle (MFB) and substantia nigra compact (SNC). We evaluated the gait changes in these models by using a computer-assisted CatWalk system. Correlations of gait parameters with tyrosine hydroxylase protein levels in the CPU and SNC were also investigated. The gait readouts were significantly impaired in both the MFB and SNC groups. However, the MFB group showed a more pronounced impairment than the SNC group. In contrast, only mild and incomplete gait impairment occurred in the CPU group. In addition, some gait parameters demonstrated close correlation with the protein levels of TH. This paper suggests that the 6-hydroxydopamine-induced MFB model is more propitious to study gait dysfunction than the other two models and the CatWalk system can provide reliable and objective criteria to stratify gait changes arising from 6-hydroxydopamine lesioned rats. These findings may hold promise in the study of PD disease progression and new therapeutic methods. © 2014 Elsevier Ireland Ltd.All rights reserved.


PubMed | Neuroscience Research Institute of North Carolina, Southern Medical University and CAS Institute of Psychology
Type: | Journal: Experimental neurology | Year: 2016

Oscillatory activity has been well-studied in many structures within cortico-basal ganglia circuits, but it is not well understood within the pedunculopontine nucleus (PPN), which was recently introduced as a potential target for the treatment of gait and postural impairments in advanced stages of Parkinsons disease (PD). To investigate oscillatory activity in the PPN and its relationship with oscillatory activity in cortico-basal ganglia circuits, we simultaneously recorded local field potentials in the PPN, primary motor cortex (M1), and subthalamic nucleus (STN) of 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats during resting and walking. After analysis of power spectral density, coherence, and partial Granger causality, three major findings emerged: 1) after 6-OHDA lesions, beta band oscillations were enhanced in all three regions during walking; 2) the direction of information flow for beta oscillations among the three structures was STNM1, STNPPN, and PPNM1; 3) after the treatment of levodopa, beta activity in the three regions was reduced significantly and the flow of beta band was also abrogated. Our results suggest that beta activity in the PPN is transmitted from the basal ganglia and probably comes from the STN, and the STN plays a dominant role in the network of causal interactions for beta activity. Thus, the STN may be a potential source of aberrant beta band oscillations in PD. Levodopa can inhibit beta activity in the PPN of parkinsonian rats but cannot relieve parkinsonian patients axial symptoms clinically. Therefore, beta oscillations may not be the major cause of axial symptoms.


Alcohol-preferring (P) rats develop high ethanol intake over several weeks of water/10% ethanol (10E) choice drinking. However, it is not yet clear precisely what components of drinking behavior undergo modification to achieve higher intake. Our concurrent report compared precisely measured daily intake in P vs. non-selected Wistar and Sprague Dawley (SD) rats. Here we analyze their drinking patterns and bouts to clarify microbehavioral components that are common to rats of different genetic backgrounds, vs. features that are unique to each. Under sole-fluid conditions P, Wistar and SD rats all consumed water at a high initial rate followed by a slow maintenance phase, but 10E - in a distinctly different step-like pattern of evenly distributed bouts. During choice period, 10E vs. water patterns for P rat appeared as an overlap of sole-fluid patterns. The SD rat choice patterns resembled sole-fluid patterns but were less regular. Choice patterns in Wistar differed from both P and SD rats, by consisting of intermixed small frequent episodes of drinking both 10E and water. Wistar and SD rats increased choice ethanol intake by elevating the number of bouts. A key finding was that P rat increased choice ethanol intake through a gradual increase of the bout size and duration, but kept bout number constant. This supports the hypothesis that genetic selection modifies microbehavioral machinery controlling drinking bout initiation, duration, and other pattern features. Precision analysis of drinking patterns and bouts allows differentiation between genetic lines, and provides a venue for study of localized circuit and transmitter influences mediating mesolimbic control over ethanol consumption.


PubMed | Neuroscience Research Institute of North Carolina
Type: | Journal: Physiology & behavior | Year: 2013

The goal of this study was to clarify similar and distinctly different parameters of fluid intake during early phases of ethanol and water choice drinking in alcohol preferring P-rat vs. non-selected Wistar and Sprague Dawley (SD) rats. Precision information on the drinking amounts and timing is needed to analyze micro-behavioral components of the acquisition of ethanol intake and to enable a search for its causal activity patterns within individual CNS circuits. The experiment followed the standard ethanol-drinking test used in P-rat selective breeding, with access to water, then 10% ethanol (10E) as sole fluids, and next to ethanol/water choice. The novelty of the present approach was to eliminate confounding prandial elevations of fluid intake, by time-separating daily food from fluid access. P-rat higher initial intakes of water and 10E as sole fluids suggest adaptations to ethanol-induced dehydration in P vs. Wistar and SD rats. P-rat starting and overall ethanol intake during the choice period were the highest. The absolute extent of ethanol intake elevation during choice period was greatest in Wistar and their final intake levels approached those of P-rat, contrary to the hypothesis that selection would produce the strongest elevation of ethanol intake. The total daily fluid during ethanol/water choice period was strikingly similar between P, Wistar and SD rats. This supports the hypothesis for a universal system that gauges the overall intake volume by titrating and integrating ethanol and water drinking fluctuations, and indicates a stable daily level of total fluid as a main regulated parameter of fluid intake across the three lines in choice conditions. The present findings indicate that a stable daily level of total fluid comprises an independent physiological limit for daily ethanol intake. Ethanol drinking, in turn, stays under the ceiling of this limit, driven by a parallel mechanism of ethanol/water choice.


PubMed | Neuroscience Research Institute of North Carolina, Southern Medical University and CAS Institute of Psychology
Type: Journal Article | Journal: Journal of Korean Neurosurgical Society | Year: 2015

The aim of this study was to investigate voluntary wheel running behavior in the unilateral 6-hydroxydopamine (6-OHDA) rat model.Male Sprague-Dawley rats were assigned to 2 groups : 6-OHDA group (n=17) and control group (n=8). The unilateral 6-OHDA rat model was induced by injection of 6-OHDA into unilateral medial forebrain bundle using a stereotaxic instrument. Voluntary wheel running activity was assessed per day in successfully lesioned rats (n=10) and control rats. Each behavioral test lasted an hour. The following parameters were investigated during behavioral tests : the number of running bouts, the distance moved in the wheel, average peak speed in running bouts and average duration from the running start to the peak speed.The number of running bouts and the distance moved in the wheel were significantly decreased in successfully lesioned rats compared with control rats. In addition, average peak speed in running bouts was decreased, and average duration from the running start to the peak speed was increased in lesioned animals, which might indicate motor deficits in these rats. These behavioral changes were still observed 42 days after lesion.Voluntary wheel running behavior is impaired in the unilateral 6-OHDA rat model and may represent a useful tool to quantify motor deficits in this model.

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