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Pars Reticulata (par + reticulata)
Kinds of Pars Reticulata Selected AbstractsAcute action of rotenone on nigral dopaminergic neurons , involvement of reactive oxygen species and disruption of Ca2+ homeostasisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2009Peter S. Freestone Abstract Rotenone is a toxin used to generate animal models of Parkinson's disease; however, the mechanisms of toxicity in substantia nigra pars compacta (SNc) neurons have not been well characterized. We have investigated rotenone (0.05,1 ,m) effects on SNc neurons in acute rat midbrain slices, using whole-cell patch-clamp recording combined with microfluorometry. Rotenone evoked a tolbutamide-sensitive outward current (94 ± 15 pA) associated with increases in intracellular [Ca2+] ([Ca2+]i) (73.8 ± 7.7 nm) and intracellular [Na+] (3.1 ± 0.6 mm) (all with 1 ,m). The outward current was not affected by a high ATP level (10 mm) in the patch pipette but was decreased by Trolox. The [Ca2+]i rise was abolished by removing extracellular Ca2+, and attenuated by Trolox and a transient receptor potential M2 (TRPM2) channel blocker, N -(p -amylcinnamoyl) anthranilic acid. Other effects included mitochondrial depolarization (rhodamine-123) and increased mitochondrial reactive oxygen species (ROS) production (MitoSox), which was also abolished by Trolox. A low concentration of rotenone (5 nm) that, by itself, did not evoke a [Ca2+]i rise resulted in a large (46.6 ± 25.3 nm) Ca2+ response when baseline [Ca2+]i was increased by a ,priming' protocol that activated voltage-gated Ca2+ channels. There was also a positive correlation between ,naturally' occurring variations in baseline [Ca2+]i and the rotenone-induced [Ca2+]i rise. This correlation was not seen in non-dopaminergic neurons of the substantia nigra pars reticulata (SNr). Our results show that mitochondrial ROS production is a key element in the effect of rotenone on ATP-gated K+ channels and TRPM2-like channels in SNc neurons, and demonstrate, in these neurons (but not in the SNr), a large potentiation of rotenone-induced [Ca2+]i rise by a small increase in baseline [Ca2+]i. [source] Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Salvatore Galati Abstract To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN-DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92,3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear-cut increase in cyclic guanosine 3',5'-monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus-synchronized activation of the STN target, SNr. Our findings suggest that, during STN-DBS, a critical change towards a high-frequency oscillatory discharge occurs. [source] The subcellular localization of GABAB receptor subunits in the rat substantia nigraEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003Justin Boyes Abstract The inhibitory effects of GABA within the substantia nigra (SN) are mediated in part by metabotropic GABAB receptors. To better understand the mechanisms underlying these effects, we have examined the subcellular localization of the GABAB receptor subunits, GABAB1 and GABAB2, in SN neurons and afferents using pre-embedding immunocytochemistry combined with anterograde or retrograde labelling. In both the SN pars compacta (SNc) and pars reticulata (SNr), GABAB1 and GABAB2 showed overlapping, but distinct, patterns of immunolabelling. GABAB1 was more strongly expressed by putative dopaminergic neurons in the SNc than by SNr projection neurons, whereas GABAB2 was mainly expressed in the neuropil of both regions. Immunogold labelling for GABAB1 and GABAB2 was localized in presynaptic and postsynaptic elements throughout the SN. The majority of labelling was intracellular or was associated with extrasynaptic sites on the plasma membrane. In addition, labelling for both subunits was found on the presynaptic and postsynaptic membranes at symmetric, putative GABAergic synapses, including those formed by anterogradely labelled striatonigral and pallidonigral terminals. Labelling was also observed on the presynaptic membrane and at the edge of the postsynaptic density at asymmetric, putative excitatory synapses. Double immunolabelling, using the vesicular glutamate transporter 2, revealed the glutamatergic nature of many of the immunogold-labelled asymmetric synapses. The widespread distribution of GABAB subunits in the SNc and SNr suggests that GABAB -mediated effects in these regions are likely to be more complex than previously described, involving presynaptic autoreceptors and heteroreceptors, and postsynaptic receptors on different populations of SN neurons. [source] Increased responsivity of glutamate release from the substantia nigra pars reticulata to striatal NMDA receptor blockade in a model of Parkinson's disease.EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2000A dual probe microdialysis study in hemiparkinsonian rats Abstract Dual probe microdialysis was employed in freely moving 6-hydroxydopamine (6-OHDA) hemilesioned rats to investigate the effects of blockade of N-methyl-D-aspartate (NMDA) receptors in the dorsolateral striatum on glutamate (Glu) release from the ipsilateral substantia nigra pars reticulata (SNr). Perfusion for 60 min with the NMDA antagonist dizocilpine (0.1 and 1 ,m) in the dopamine (DA)-denervated striatum stimulated nigral Glu release (peak effect of 139 ± 7% and 138 ± 9%, respectively). The lower (0.01 ,m) and higher (10 ,m) concentrations were ineffective. In sham-operated rats, dizocilpine failed to affect nigral Glu release up to 1 ,m but induced a prolonged stimulation at 10 ,m (153 ± 9% at the end of perfusion). The present results show that DA-deficiency in the striatum of hemiparkinsonian rats is associated with increased responsivity of nigral Glu release to striatal NMDA receptor blockade. This suggests that changes of NMDA receptor mediated control of the striatofugal pathways occur during Parkinson's disease (PD). [source] Influence of the frequency parameter on extracellular glutamate and ,-aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003François Windels Abstract High-frequency stimulation (HFS) of the subthalamic nucleus (STN) proves to be an efficient treatment for alleviating motor symptoms in Parkinson's disease (PD). However, the mechanisms of HFS underlying these clinical effects remain unknown. Using intracerebral microdialysis, we previously reported that HFS induces, in normal rats, a significant increase of extracellular glutamate (Glu) in the globus pallidus (GP in rats or GPe in primates) and the substantia nigra pars reticulata (SNr), whereas ,-aminobutyric acid (GABA) was increased only in the SNr. Bradykinesia can be improved by STN stimulation in a frequency-dependent manner, a plateau being reached around 130 Hz. The aim of the present study was to determine whether neurochemical changes are also frequency dependent. Electrical STN stimulation was applied at various frequencies (10, 60, 130, and 350 Hz) in normal rats. The results show that, for Glu, the amplitude of increase detected in GP and SNr is maximal at 130 Hz and is maintained at 350 Hz. No modifications of GABA were observed in GP whatever the frequency applied, whereas, in SNr, GABA increased from 60 to 350 Hz. Our results provide new neurochemical data implicating STN target structures in deep-brain-stimulation mechanisms. © 2003 Wiley-Liss, Inc. [source] Ultrastructural and MRI study of the substantia nigra evolving exofocal post-ischemic neuronal death in the ratNEUROPATHOLOGY, Issue 3 2002Fengyu Zhao To clarify the morphological characteristics of exofocal post-ischemic neuronal death (EPND) in the substantia nigra (SN), we investigated the course of light- and electron-microscopic changes of the SN of rats subjected to occlusion of the left middle cerebral artery (MCA) for 1, 2, 4, 7 and 12 days. To assess cellular edema, sequential magnetic resonance (MR) mapping of the apparent diffusion coefficient (ADC) and the T2 value test was performed. Histological and electron-microscopic examination on day 1 showed dotted chromatin clumps in the nuclei of some neurons and mild swelling of the perivascular endfeet of astrocytes in the ipsilateral SN. On day 2, a few cells of the ipsilateral SN pars reticulata (SNr) revealed key morphological signs of apoptosis , apoptotic body-like condensation and segregation of the chromatin and DNA fragmentation-like nuclear remnants. On day 4, 38% of neurons became swollen (pale neurons) with cytoplasmic microvacuoles, which appeared to originate from rough endoplasmic reticulum (rER), mitochondria and Golgi apparatus. Twenty percent of neurons showed massive proliferation of the cisternae of the rER, some of which were fragmented or had lost their normal parallel arrangement. In addition, MR mapping revealed a transient ADC decrease with a T2 increase (signifying a phase of cellular edema), which coordinated with the phase of ultrastructural cellular swelling. Further, the total number of neurons started to decrease gradually, the perivascular endfeet of astrocytes were markedly swollen, and the neuropil became loose on day 4. On day 7, reactive astrocytes and dark neurons occurred most frequently. These results suggest that the EPND in the SN after occlusion of the MCA in adult rats is due to both apoptosis and necrosis, although necrosis seems to be the dominant mechanism of the EPND. However, the morphologic resemblances of EPND to delayed neuronal death suggest these processes have a common pathomechanism. [source] Downregulation of glial glutamate transporters after dopamine denervation in the striatum of 6-hydroxydopamine-lesioned ratsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2008E.K.Y. Chung Abstract Overactivity of glutamatergic neurotransmission in the basal ganglia is known to be closely related to the onset and pathogenesis of Parkinson's disease. Glutamate homeostasis around glutamatergic synapses is tightly regulated by two groups of glutamate transporters: glial glutamate transporters GLT1 (EAAT2) and GLAST (EAAT1), and neuronal glutamate transporter EAAC1. In order to investigate the changes of glutamate transporters after the onset of Parkinson's disease, unilateral 6-hydroxydopamine-lesioned rat, an animal model of Parkinson's disease, was employed. By immunofluorescence and Western blot analyses, GLT1 and GLAST proteins were significantly reduced in the striatum with lesion. No change in GLT1 and GLAST protein was found in the substantia nigra. The reduction of GLT1 protein in the striatum was more prominent than that of GLAST protein (,40% vs. 20%). In addition, EAAC1 protein was found to be increased in the substantia nigra pars reticulata of the lesioned rats but not in the striatum. The present results indicate that reductions of GLT1 and GLAST may impair glutamate homeostasis around glutamatergic synapses in the striatum and contribute to over-spills of glutamate in the system. An increase in the EAAC1 level in the substantia nigra pars reticulata may increase GABA synthesis and enhance GABAergic neurotransmission. These results indicate that there are differential and distinct modulations of glutamate transporters after dopamine denervation in the 6-hydroxydopamine-lesioned rat. J. Comp. Neurol. 511:421,437, 2008. © 2008 Wiley-Liss, Inc. [source] Comparative cellular distribution of GABAA and GABAB receptors in the human basal ganglia: Immunohistochemical colocalization of the ,1 subunit of the GABAA receptor, and the GABABR1 and GABABR2 receptor subunitsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2004Henry J. Waldvogel Abstract The GABAB receptor is a G-protein linked metabotropic receptor that is comprised of two major subunits, GABABR1 and GABABR2. In this study, the cellular distribution of the GABABR1 and GABABR2 subunits was investigated in the normal human basal ganglia using single and double immunohistochemical labeling techniques on fixed human brain tissue. The results showed that the GABAB receptor subunits GABABR1 and GABABR2 were both found on the same neurons and followed the same distribution patterns. In the striatum, these subunits were found on the five major types of interneurons based on morphology and neurochemical labeling (types 1, 2, 3, 5, 6) and showed weak labeling on the projection neurons (type 4). In the globus pallidus, intense GABABR1 and GABABR2 subunit labeling was found in large pallidal neurons, and in the substantia nigra, both pars compacta and pars reticulata neurons were labeled for both receptor subunits. Studies investigating the colocalization of the GABAA ,1 subunit and GABAB receptor subunits showed that the GABAA receptor ,1 subunit and the GABABR1 subunit were found together on GABAergic striatal interneurons (type 1 parvalbumin, type 2 calretinin, and type 3 GAD neurons) and on neurons in the globus pallidus and substantia nigra pars reticulata. GABABR1 and GABABR2 were found on substantia nigra pars compacta neurons but the GABAA receptor ,1 subunit was absent from these neurons. The results of this study provide the morphological basis for GABAergic transmission within the human basal ganglia and provides evidence that GABA acts through both GABAA and GABAB receptors. That is, GABA acts through GABAB receptors, which are located on most of the cell types of the striatum, globus pallidus, and substantia nigra. GABA also acts through GABAA receptors containing the ,1 subunit on specific striatal GABAergic interneurons and on output neurons of the globus pallidus and substantia nigra pars reticulata. J. Comp. Neurol. 470:339,356, 2004. © 2004 Wiley-Liss, Inc. [source] Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the ratTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Andrew Sharott Population activity in cortico-basal ganglia circuits is synchronized at different frequencies according to brain state. However, the structures that are likely to drive the synchronization of activity in these circuits remain unclear. Furthermore, it is not known whether the direction of transmission of activity is fixed or dependent on brain state. We have used the directed transfer function (DTF) to investigate the direction in which coherent activity is effectively driven in cortico-basal ganglia circuits. Local field potentials (LFPs) were simultaneously recorded in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr), together with the ipsilateral frontal electrocorticogram (ECoG) of anaesthetized rats. Directional analysis was performed on recordings made during robust cortical slow-wave activity (SWA) and ,global activation'. During SWA, there was coherence at ,1 Hz between ECoG and basal ganglia LFPs, with much of the coherent activity directed from cortex to basal ganglia. There were similar coherent activities at ,1 Hz within the basal ganglia, with more activity directed from SNr to GP and STN, and from STN to GP rather than vice versa. During global activation, peaks in coherent activity were seen at higher frequencies (15,60 Hz), with most coherence also directed from cortex to basal ganglia. Within the basal ganglia, however, coherence was predominantly directed from GP to STN and SNr. Together, these results highlight a lead role for the cortex in activity relationships with the basal ganglia, and further suggest that the effective direction of coupling between basal ganglia nuclei is dynamically organized according to brain state, with activity relationships involving the GP displaying the greatest capacity to change. [source] |