scholarly journals Diverse Short-Term Dynamics of Inhibitory Synapses Converging on Striatal Projection Neurons: Differential Changes in a Rodent Model of Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Janet Barroso-Flores ◽  
Marco A. Herrera-Valdez ◽  
Violeta Gisselle Lopez-Huerta ◽  
Elvira Galarraga ◽  
José Bargas
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Voltage ◽  
Rodent Model ◽  
Inhibitory Synapses ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Dopamine Depletion ◽  
Short Term ◽  
6 Hydroxydopamine

Most neurons in the striatum are projection neurons (SPNs) which make synapses with each other within distances of approximately 100 µm. About 5% of striatal neurons are GABAergic interneurons whose axons expand hundreds of microns. Short-term synaptic plasticity (STSP) between fast-spiking (FS) interneurons and SPNs and between SPNs has been described with electrophysiological and optogenetic techniques. It is difficult to obtain pair recordings from some classes of interneurons and due to limitations of actual techniques, no other types of STSP have been described on SPNs. Diverse STSPs may reflect differences in presynaptic release machineries. Therefore, we focused the present work on answering two questions: Are there different identifiable classes of STSP between GABAergic synapses on SPNs? And, if so, are synapses exhibiting different classes of STSP differentially affected by dopamine depletion? Whole-cell voltage-clamp recordings on SPNs revealed three classes of STSPs: depressing, facilitating, and biphasic (facilitating-depressing), in response to stimulation trains at 20 Hz, in a constant ionic environment. We then used the 6-hydroxydopamine (6-OHDA) rodent model of Parkinson’s disease to show that synapses with different STSPs are differentially affected by dopamine depletion. We propose a general model of STSP that fits all the dynamics found in our recordings.

Upregulation of D2-class signaling in dopamine-denervated striatum is in part mediated by D3 receptors acting on CaV2.1 channels via PIP2 depletion

2011 ◽  
Vol 105 (5) ◽  
pp. 2260-2274 ◽  
Author(s):  
G. Aleph Prieto ◽  
Azucena Perez-Burgos ◽  
Marcela Palomero-Rivero ◽  
Elvira Galarraga ◽  
Rene Drucker-Colin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Intracellular Signaling ◽  
Cell Voltage ◽  
Gaba Release ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Dopamine Depletion ◽  
R And D ◽  
Relative Contribution ◽  
6 Hydroxydopamine

The loss of dopaminergic neurons in the substantia nigra compacta followed by striatal dopamine depletion is a hallmark of Parkinson's disease. After dopamine depletion, dopaminergic D2 receptor (D2R)-class supersensitivity develops in striatal neurons. The supersensitivity results in an enhanced modulation of Ca2+ currents by D2R-class receptors. However, the relative contribution of D2R, D3R, and D4R types to the supersensitivity, as well as the mechanisms involved, have not been elucidated. In this study, whole cell voltage-clamp recordings were performed to study Ca2+ current modulation in acutely dissociated striatal neurons obtained from rodents with unilateral 6-hydroxydopamine lesions in the substantia nigra compacta. Selective antagonists for D2R, D3R, and D4R types were used to identify whether the modulation by one of these receptors experiences a selective change after dopaminergic denervation. It was found that D3R-mediated modulation was particularly enhanced. Increased modulation targeted CaV2.1 (P/Q) Ca2+ channels via the depletion of phosphatidylinositol 4,5-bisphosphate, an intracellular signaling cascade hard to detect in control neurons and hypothesized as being amplified by dopamine depletion. An imbalance in the striatal expression of D3R and its splice variant, D3nf, accompanied enhanced D3R activity. Because CaV2.1 Ca2+ channels mediate synaptic GABA release from the terminals of striatal neurons, reinforcement of their inhibition by D3R may explain in part the profound decrease in synaptic strength in the connections among striatal projection neurons observed in the dopamine-depleted striatum.

Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson's disease

2010 ◽  
Vol 1328 ◽  
pp. 139-151 ◽  
Author(s):  
Mohd.Moshahid Khan ◽  
Ajmal Ahmad ◽  
Tauheed Ishrat ◽  
M. Badruzzaman Khan ◽  
Md. Nasrul Hoda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oxidative Damage ◽  
Rat Model ◽  
Dopamine Depletion ◽  
6 Hydroxydopamine

scholarly journals Parallel Movement-suppressing Striatal Output Pathways

2020 ◽  
Author(s):  
Qiaoling Cui ◽  
Xixun Du ◽  
Isaac Y. M. Chang ◽  
Arin Pamukcu ◽  
Varoth Lilascharoen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Body Movement ◽  
Disease Model ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Striatal Projection Neurons ◽  
6 Hydroxydopamine

AbstractThe classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and how they are involved in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting role of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson’s disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLSdSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson’s disease that has not been previously considered.Significance statementIn the classic basal ganglia model, the striatum is described as a divergent structure—it controls motor and adaptive functions through two segregated, opponent output streams. However, the experimental results that show the projection from direct-pathway neurons to the external pallidum have been largely ignored. Here, we showed that this striatopallidal sub-pathway targets a select subset of neurons in the external pallidum and is motor-suppressing. We found that this sub-pathway undergoes plastic changes in a Parkinson’s disease model. In particular, our results suggest that the increase in strength of this sub-pathway contributes to the slowness or reduced movements observed in Parkinson’s disease.

Ultrastructure of Striatal Dopamine Synapses in Rats with Striatal Dopamine Depletion

2001 ◽  
Vol 7 (S2) ◽  
pp. 660-661
Author(s):  
W. Gray (Jay) Jerome ◽  
Thomas J. Montine ◽  
Ariel Y. Deutch
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Striatal Dopamine ◽  
Medium Spiny Neurons ◽  
Dopamine Depletion ◽  
Proximate Cause ◽  
Spiny Neurons ◽  
Neuronal Reorganization ◽  
Striatal Dopamine Depletion ◽  
6 Hydroxydopamine

Parkinson's disease (PD) is characterized by rigidity, tremor, bradykinesia, and postural instability. The proximate cause of these symptoms is striatal dopamine (DA) insufficiency. The motor symptoms of PD can be alleviated by DA replacement therapy. However, late in the course of the disease patients appear to become less responsive to DA replacement. This therapeutic change suggests the possibility of structural and/or functional defects in striatal medium spiny neurons, which receive convergent DA and cortical (glutamate) inputs.To understand the neuronal reorganization occurring in Parkinson's disease, we used ultrastructural methods to examine the striatum of rats with striatal dopaminergic deafferentation induced by unilateral intranigral injection of 6-hydroxydopamine. After a six month survival, rats were deeply anesthetized with pentobarbital and perfused with 4% paraformaldehyde-1 % glutaraldehdyde solution in 0.1M Sorenson's phosphate buffer (pH 7.4). The brains were removed, post-fixed for 12 hours, embedded in paraffin, and coronal sections cut through the striatum and midbrain.

scholarly journals Do human recordings reveal drastic modulations in the discharge of striatal projection neurons in Parkinson’s disease?

2020 ◽  
Author(s):  
Dan Valsky ◽  
Zvi Israel ◽  
Thomas Boraud ◽  
Hagai Bergman ◽  
Marc Deffains
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Neuronal Activity ◽  
Discharge Rate ◽  
Projection Neurons ◽  
Dopamine Depletion ◽  
Striatal Projection Neurons ◽  
Deep Brain

AbstractDopamine depletion of the striatum plays a key role in the pathophysiology of Parkinson’s disease (PD), but our understanding of the changes in the discharge rate and pattern of the striatal projection neurons (SPNs) remains limited. Here, we recorded multi-unit signals from the striatum of PD (N = 934) and dystonic (N = 718) patients undergoing deep brain stimulation surgeries. Using an innovative automated data-driven approach to classify striatal units, we showed that the SPN discharge rate is inversely proportional to the isolation quality and stationarity of the SPNs. In contrast to earlier studies in both PD patients and the non-human primate model of PD, we found no drastic changes in the spiking activity (discharge rate and pattern) of the well-isolated and stationary SPNs of PD patients compared to either dystonic patients or the normal levels of striatal activity reported in healthy animals. Moreover, cluster analysis using SPN discharge properties did not characterize two well-separated SPN subpopulations. There was therefore no specific SPN subpopulation (D1 or D2 SPNs) strongly affected by the pathological state. Instead, our results suggest that moderate changes in SPN discharge are most likely amplified by basal ganglia downstream structures, thus leading to the clinical (motor and non-motor) symptoms of PD.Significance statementIn Parkinson’s disease (PD), the loss of the midbrain dopaminergic neurons leads to massive striatal dopamine depletion that provokes abnormal activity throughout the basal ganglia. However, the impact of dopamine depletion on neuronal activity in the striatum is still highly debated. We recorded and examined the neuronal activity in striatum of PD and dystonic patients undergoing deep brain stimulation surgeries. We found that striatal activity was not drastically higher in PD patients compared to either dystonic patients or the normal levels of striatal activity reported in animal studies. In PD, moderate changes in striatal basal activity are therefore most likely amplified by basal ganglia downstream structures.

scholarly journals Synchrotron FTIR Microspectroscopy Study of the Striatum in 6-Hydroxydopamine Rat Model of Parkinson's Disease

2012 ◽  
Vol 27 ◽  
pp. 229-238 ◽  
Author(s):  
Zhu Hongyan ◽  
Pei Xiao ◽  
Wu Lingyan ◽  
Liu Bo ◽  
Qi Zeming ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Protein Secondary Structure ◽  
Nigrostriatal Pathway ◽  
Spectral Absorption ◽  
Striatal Neurons ◽  
Ftir Microspectroscopy ◽  
6 Hydroxydopamine ◽  
High Level

In the present study, synchrotron-based Fourier transform-infrared (FTIR) microspectroscopy is used to analyze the biochemical composition of the striatal neurons in normal and Parkinson's disease (PD) rat brain tissues. The rat model of Parkinson's disease is established by destroying the nigrostriatal pathway with 6-hydroxydopamine (6-OHDA). The detailed spectral analyses show the significant changes of cellular compositions such as lipids, and proteins in the striatal neurons of 6-OHDA-lesioned PD rats with respect to control neurons. As a result, the intensities of spectral absorption assigned to lipid of the striatal neurons in PD rats are higher than in control animals. Furthermore, the unsaturation levels of phospholipids decrease in PD neurons with respect to control neurons, indicating a high level of lipid peroxidation. The analysis of protein secondary structure shows the significantly higher ratio ofβ-sheet in PD neurons compared to that of control neurons, suggesting that the abnormal protein structure occurs before their morphological appearances in the striatal neurons. These findings suggest that the biochemical changes in neurons could be involved in the pathogenesis of Parkinson's disease.

Sign in / Sign up

Export Citation Format

Share Document