Bursting in Substantia Nigra Pars Reticulata Neurons In Vitro: Possible Relevance for Parkinson Disease

2007 ◽  
Vol 98 (4) ◽  
pp. 2311-2323 ◽  
Author(s):  
Osvaldo Ibáñez-Sandoval ◽  
Luis Carrillo-Reid ◽  
Elvira Galarraga ◽  
Dagoberto Tapia ◽  
Ernesto Mendoza ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Parkinson Disease ◽  
Temporal Structure ◽  
Projection Neurons ◽  
Rate Model ◽  
Indirect Pathway ◽  
Bath Application ◽  
Pattern Generators ◽  
Oscillatory Model

Projection neurons of the substantia nigra reticulata (SNr) convey basal ganglia (BG) processing to thalamocortical and brain stem circuits responsible for movement. Two models try to explain pathological BG performance during Parkinson disease (PD): the rate model, which posits an overexcitation of SNr neurons due to hyperactivity in the indirect pathway and hypoactivity of the direct pathway, and the oscillatory model, which explains PD as the product of pathological pattern generators disclosed by dopamine reduction. These models are, apparently, incompatible. We tested the predictions of the rate model by increasing the excitatory drive and reducing the inhibition on SNr neurons in vitro. This was done pharmacologically with bath application of glutamate agonist N-methyl-d-aspartate and GABAA receptor blockers, respectively. Both maneuvers induced bursting behavior in SNr neurons. Therefore synaptic changes forecasted by the rate model induce the electrical behavior predicted by the oscillatory model. In addition, we found evidence that CaV3.2 Ca2+ channels are a critical step in generating the bursting firing pattern in SNr neurons. Other ion channels involved are: hyperpolarization-activated cation channels, high-voltage-activated Ca2+ channels, and Ca2+-activated K+ channels. However, although these channels shape the temporal structure of bursting, only CaV3.2 Ca2+ channels are indispensable for the initiation of the bursting pattern.

scholarly journals Neuromodulation of excitatory synaptogenesis in striatal development

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Yevgenia Kozorovitskiy ◽  
Rui Peixoto ◽  
Wengang Wang ◽  
Arpiar Saunders ◽  
Bernardo L Sabatini
Keyword(s):  
Developmental Plasticity ◽  
Synapse Formation ◽  
Glutamate Release ◽  
Projection Neurons ◽  
Excitatory Synapses ◽  
Indirect Pathway ◽  
Protein Receptors ◽  
In Vivo Effects

Dopamine is released in the striatum during development and impacts the activity of Protein Kinase A (PKA) in striatal spiny projection neurons (SPNs). We examined whether dopaminergic neuromodulation regulates activity-dependent glutamatergic synapse formation in the developing striatum. Systemic in vivo treatment with Gαs-coupled G-protein receptors (GPCRs) agonists enhanced excitatory synapses on direct pathway striatal spiny projection neurons (dSPNs), whereas rapid production of excitatory synapses on indirect pathway neurons (iSPNs) required the activation of Gαs GPCRs in SPNs of both pathways. Nevertheless, in vitro Gαs activation was sufficient to enhance spinogenesis induced by glutamate photolysis in both dSPNs and iSPNs, suggesting that iSPNs in intact neural circuits have additional requirements for rapid synaptic development. We evaluated the in vivo effects of enhanced glutamate release from corticostriatal axons and postsynaptic PKA and discovered a mechanism of developmental plasticity wherein rapid synaptogenesis is promoted by the coordinated actions of glutamate and postsynaptic Gαs-coupled receptors.

scholarly journals Conservation of the direct and indirect pathways dichotomy in mouse caudal striatum with uneven distribution of dopamine receptor D1- and D2-expressing neurons

2021 ◽  
Author(s):  
Kumiko Ogata ◽  
Fuko Kadono ◽  
Yasuharu Hirai ◽  
Ken-ichi Inoue ◽  
Masahiko Takada ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopamine Receptor ◽  
Common Marmoset ◽  
Projection Neuron ◽  
Membrane Properties ◽  
Electrophysiological Recording ◽  
Projection Neurons ◽  
The Poor ◽  
Neural Tracing

The striatum is one of the key nuclei for adequate control of voluntary behaviors and reinforcement learning. Two striatal projection neuron types, expressing either dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R) constitute two independent output routes: the direct or indirect pathways, respectively. These pathways co-work in balance to achieve coordinated behavior. Two projection neuron types are equivalently intermingled in most striatal space. However, recent studies revealed two atypical zones in the caudal striatum: the zone in which D1R-neurons are the minor population (D1R-poor zone) and that in which D2R-neurons are the minority (D2R-poor zone). It remains obscure as to whether these imbalanced zones have similar properties on axonal projections and electrophysiology to other striatal regions. Based on morphological experiments in mice using immunofluorescence, in situ hybridization, and neural tracing, here, we revealed the poor zones densely projected to the globus pallidus and substantia nigra pars lateralis, with a few collaterals in substantia nigra pars reticulata and compacta. As other striatal regions, D1R-neurons were the direct pathway neurons, while projection neurons in the poor zones possessed similar electrophysiological membrane properties to those in the conventional striatum using in vitro electrophysiological recording. In addition, the poor zones existed irrespective of the age of mice. We also identified the poor zones in the common marmoset as well as other rodents. These results suggest that the poor zones in the caudal striatum follow the conventional projection patterns irrespective of imbalanced distribution of projection neurons. The poor zones could be an innate structure and common in mammals and relate to specific functions via highly restricted projections.

Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats

2008 ◽  
Vol 24 (3-4) ◽  
pp. E8 ◽  
Author(s):  
Karim Mukhida ◽  
Behnam A. Baghbaderani ◽  
Murray Hong ◽  
Matthew Lewington ◽  
Timothy Phillips ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Parkinson Disease ◽  
Fetal Tissue ◽  
Brain Regions ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Differentiation Potential ◽  
And Migration

Object Fetal tissue transplantation for Parkinson disease (PD) has demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion. Methods Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8–10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation. Results The HNPCs isolated from various regions of the neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed. Conclusions Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.

scholarly journals Targeting epigenetic mechanisms in Parkinson’s disease: HDAC1 inhibitor LG325 modulates circuitry imbalance

2019 ◽  
Author(s):  
Catarina Cunha ◽  
Maria Novella Romanelli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Laser Scanning ◽  
Neurodegenerative Disorder ◽  
Hdac Inhibitors ◽  
Laser Scanning Microscopy ◽  
Projection Neurons ◽  
Genetic Associations ◽  
Indirect Pathway ◽  
Bath Application

Parkinson's disease (PD) is a prevalent neurodegenerative disorder worldwide that affects the US alone ca. 1 million people. There is limited evidence for genetic associations with PD; however, recent research proposes epigenetics as a mechanism involved in PD's development and progression. Especially histone deacetylase (HDAC) inhibitors were shown to recuperate synaptic plasticity, learning, and memory in several neurodegenerative disorders. Therefore, we studied the effects of LG325 (specific HDAC1 inhibitor) on striatal spiny projection neurons (SPNs), which are known to be involved in PD motor dysfunctions, targeting direct pathway SPNs (dSPNs) and indirect pathway SPNs (iSPNs) separately by performing 2-photon laser scanning microscopy in BAC transgenic drd1a-tdTomato and drd2-GFP transgenic mice. We evoked single back-propagating action potentials (bAP) that cause a somewhat higher elevation in cytosolic Ca2+ concentration at distal dendritic locations in iSPNs compared to dSPNs. Bath application of 1 µM LG325 lead to a marked decrease in the bAPs evoked dendritic Ca2+ entry in dSPNs. We propose that HDAC1 inhibition could possibly not only alleviate the progression of PD but may also hold the potential to relieve acutely motor symptoms in PD patients. HDAC1 inhibitors should be further investigated and considered a treatment option, especially in patients who have reached a resistance to dopamine-related treatments.

Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell
Keyword(s):  
Brain Stem ◽  
Respiratory Activity ◽  
Dependent Manner ◽  
Frequency Increase ◽  
Burst Frequency ◽  
Bath Application ◽  
Burst Amplitude ◽  
Dose Dependent ◽  
The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

scholarly journals Substantia nigra neuromelanin magnetic resonance imaging in patients with different subtypes of Parkinson disease

2021 ◽  
Author(s):  
Lu Wang ◽  
Yayun Yan ◽  
Liyao Zhang ◽  
Yan Liu ◽  
Ruirui Luo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Clinical Symptoms ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Resonance Imaging ◽  
Mean Values

AbstractNeuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.

scholarly journals Utility of manual fractional anisotropy measurements in the management of patients with Parkinson disease: a feasibility study with a 1.5-T magnetic resonance imaging system

2021 ◽  
Vol 10 (2) ◽  
pp. 205846012199347
Author(s):  
Romulo V de Oliveira ◽  
João S Pereira
Keyword(s):  
Diffusion Tensor Imaging ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Fractional Anisotropy ◽  
Diffusion Tensor ◽  
Neuronal Damage ◽  
Magnetic Resonance Imaging System ◽  
Healthy Controls ◽  
Clinical Variables ◽  
Severity Scores

Background Diffusion tensor imaging has emerged as a promising tool for quantitative analysis of neuronal damage in Parkinson disease, with potential value for diagnostic and prognostic evaluation. Purpose The aim of this study was to examine Parkinson disease-associated alterations in specific brain regions revealed by diffusion tensor imaging and how such alterations correlate with clinical variables. Material and Methods Diffusion tensor imaging was performed on 42 Parkinson disease patients and 20 healthy controls with a 1.5-T scanner. Manual fractional anisotropy measurements were performed for the ventral, intermediate, and dorsal portions of the substantia nigra, as well as for the cerebral peduncles, putamen, thalamus, and supplementary motor area. The correlation analysis between these measurements and the clinical variables was performed using χ2 variance and multiple linear regression. Results Compared to healthy controls, Parkinson disease patients had significantly reduced fractional anisotropy values in the substantia nigra ( P < .05). Some fractional anisotropy measurements in the substantia nigra correlated inversely with duration of Parkinson disease and Parkinson disease severity scores. Reduced fractional anisotropy values in the substantia nigra were also correlated inversely with age variable. fractional anisotropy values obtained for the right and left putamen varied significantly between males and females in both groups. Conclusion Manual fractional anisotropy measurements in the substantia nigra were confirmed to be feasible with a 1.5-T scanner. Diffusion tensor imaging data can be used as a reliable biomarker of Parkinson disease that can be used to support diagnosis, prognosis, and progression/treatment monitoring.

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