Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D₂ receptor (D₂R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D₂R⁺ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D₂R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D₂-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D₂R⁺ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D₂R⁺ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D₂R⁺ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D₂R⁺ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Rats ; Animals ; Levodopa/toxicity* ; Dopamine ; Parkinsonian Disorders/drug therapy* ; Oxidopamine ; Dyskinesia, Drug-Induced ; Corpus Striatum/metabolism* ; Neurons/metabolism* ; Receptors, Dopamine D2/metabolism* ; Antiparkinson Agents/toxicity*

As an environmental risk factor, psychological stress may trigger the onset or accelerate the progression of Parkinson's disease (PD). Here, we evaluated the effects of acute restraint stress on striatal dopaminergic terminals and the brain metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which has been widely used for creating a mouse model of PD. Exposure to 2 h of restraint stress immediately after injection of a low dose of MPTP caused a severe loss of striatal dopaminergic terminals as indicated by decreases in the dopamine transporter protein and dopamine levels compared with MPTP administration alone. Both striatal 1-methyl-4-phenylpyridinium ion (MPP) and MPTP concentrations were significantly increased by the application of restraint stress. Striatal monoamine oxidase-B, which catalyzes the oxidation of MPTP to MPP, was not changed by the restraint stress. Our results indicate that the enhanced striatal dopaminergic terminal loss in the stressed mice is associated with an increase in the transport of neurotoxin into the brain.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; metabolism ; 1-Methyl-4-phenylpyridinium ; metabolism ; Animals ; Corpus Striatum ; drug effects ; metabolism ; Disease Models, Animal ; Dopaminergic Neurons ; drug effects ; MPTP Poisoning ; chemically induced ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neurotoxins ; metabolism ; Restraint, Physical ; Stress, Psychological ; metabolism

Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.
Attention Deficit Disorder with Hyperactivity ; diagnostic imaging ; genetics ; pathology ; Brain ; diagnostic imaging ; Cerebellum ; diagnostic imaging ; Child ; Corpus Striatum ; diagnostic imaging ; Female ; Frontal Lobe ; diagnostic imaging ; Genotype ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Minisatellite Repeats ; genetics ; Neural Pathways ; diagnostic imaging ; Oxygen ; blood ; Receptors, Dopamine D4 ; genetics ; metabolism ; Rest

The striatum and globus pallidus are principal nuclei of the basal ganglia. Nissl- and acetylcholinesterase-stained sections of the tree shrew brain showed the neuroanatomical features of the caudate nucleus (Cd), internal capsule (ic), putamen (Pu), accumbens, internal globus pallidus, and external globus pallidus. The ic separated the dorsal striatum into the Cd and Pu in the tree shrew, but not in rats and mice. In addition, computer-based 3D images allowed a better understanding of the position and orientation of these structures. These data provided a large-scale atlas of the striatum and globus pallidus in the coronal, sagittal, and horizontal planes, the first detailed distribution of parvalbumin-immunoreactive cells in the tree shrew, and the differences in morphological characteristics and density of parvalbumin-immunoreactive neurons between tree shrew and rat. Our findings support the tree shrew as a potential model for human striatal disorders.
Acetylcholinesterase ; metabolism ; Animals ; Brain Mapping ; Corpus Striatum ; anatomy & histology ; cytology ; metabolism ; Globus Pallidus ; anatomy & histology ; cytology ; metabolism ; Imaging, Three-Dimensional ; Male ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neurons ; metabolism ; Parvalbumins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Statistics, Nonparametric ; Tupaiidae ; anatomy & histology

OBJECTIVEIn vivo Proton Magnetic Resonance Spectroscopy (1H-MRS) can be used to evaluate the levels of specific neurochemical biomarkers of pathological mechanisms in the brain.

METHODSWe conducted T2-Weighted Magnetic Resonance Imaging (MRI) and 1H-MRS with a 3.0-Tesla animal MRI system to investigate the early microstructural and metabolic profiles in vivo in the striatum of rats following carbon monoxide (CO) poisoning.

RESULTSCompared to baseline, we found significant cortical surface deformation, cerebral edema changes, which were indicated by the unclear gray/white matter border, and lateral ventricular volume changes in the brain. A significant reduction in the metabolite to total creatine (Cr) ratios of N-acetylaspartate (NAA) was observed as early as 1 h after the last CO administration, while the lactate (Lac) levels increased marginally. Both the Lac/Cr and NAA/Cr ratios leveled off at 6 h and showed no subsequent significant changes. In addition, compared to the control, the choline (Cho)/Cr ratio was slightly reduced in the early stages and significantly increased after 6 h. In addition, a pathological examination revealed mild cerebral edema on cessation of the insult and more severe cerebral injury after additional CO poisoning.

CONCLUSIONThe present study demonstrated that 1H-MRS of the brain identified early metabolic changes after CO poisoning. Notably, the relationship between the increased Cho/Cr ratio in the striatum and delayed neuropsychologic sequelae requires further research.

Animals ; Biomarkers ; Carbon Monoxide Poisoning ; metabolism ; Corpus Striatum ; drug effects ; metabolism ; Magnetic Resonance Spectroscopy ; methods ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore action mechanism of electroacupuncture (EA) on treatment of Parkinson's disease (PD).

METHODSA total of 40 healthy male SD rats were randomly divided into a normal group, a sham operation group, a model group and an EA group, 10 rats in each group. PD rat model was duplicated by micro injection of 6-hydroxyl dopamine into right striatum of rats, and the rats in the sham operation group were treated with micro injection of 0. 9% NaCl. Rats in the normal group, model group and the sham operation group received no treatment; rats in the EA group were treated by EA at "Fengfu" (GV 16) and "Taichong" (LR 3) with continuous wave, 2 Hz in frequency, 1 mA in intensity for 30 min. The treatment was given once a day for total 2 weeks. Behavioral test was used to evaluate rotational behavior changes of PD rats. RT-PCR method was applied to detect the expression of GFAP (glial fiber acidic protein) mRNA and Cx43 (connexin 43) mRNA in the striatum.

RESULTSThe difference of rotational behavior was not significant before and after treatment in the model group (P>0. 05), while that in the EA group was significant (P<0. 01). The expression of GFAP mRNA and Cx43 mRNA in the model group was significantly higher than that in the normal group and sham operation group (all P<0. 01); after EA treatment, the expression of GFAP mRNA and Cx43 mRNA in the EA group was lower significantly than that in the model group (both P<0. 01).

CONCLUSIONThe action mechanism of EA for prevention and treatment of Parkinson' s disease may be associated with inhibiting the activation of astrocytes.

Acupuncture Points ; Animals ; Astrocytes ; Connexin 43 ; genetics ; metabolism ; Corpus Striatum ; metabolism ; Electroacupuncture ; Humans ; Male ; Nerve Tissue Proteins ; genetics ; metabolism ; Parkinson Disease ; genetics ; metabolism ; therapy ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To explore the status of apoptosis in human striatum derived neural stem cells (NSCs) aft er accutase dissociation and passage. METHODS: The NSCs were isolated from fetuses obtained through spontaneous abortion at 13- 18 weeks of pregnancy, which formed neurospheres in vitro. At passages of 3-5, the neurospheres were disassociated into single cell by accutase digestion and then passaged. At 1, 24 and 72 h after passage, the apoptosis of NSCs was measured by several methods, including active caspase-3 or TUNEL staining for fixed cells, Annexin V, Hoechst or PI staining for live cells. RESULTS: At all of the 3 time points, the staining of TUNEL and active caspase-3 overlapped perfectly. The apoptosis rate of NSCs increased significantly from 20%-25% at 1 h to 75%-80% at 24 h after passage (P<0.01). At 72 h, the apoptosis rate was significantly decreased as compared to that at 24 h time point because of the self-renewal and proliferation of survived NSCs (P<0.01). CONCLUSION Many cells in the neurospheres formed by human striatum-derived NSCs underwent apoptosis soon after accutase disassociation. For NSCs cultured in vitro, anti-apoptosis treatments might be a good method to increase the self-renewal and the proliferation of NSCs.
Apoptosis ; Caspase 3 ; metabolism ; Cells, Cultured ; Collagenases ; chemistry ; Corpus Striatum ; cytology ; Female ; Humans ; In Situ Nick-End Labeling ; Neural Stem Cells ; cytology ; Peptide Hydrolases ; chemistry ; Pregnancy

The present study is to explore the change process and distribution of phosphorylated DARPP-32 (p-DARPP-32) in rat brain including cortex, hippocampus and striatum and to further deduce whether p-DARPP-32 was possibly involved in epilepsy induced by repetitive low doses of pentylenetetrazol (PTZ). PTZ-induced epilepsy model in rat was established with 30 male SD rats randomly divided into 6 groups, control group and five trial groups [PTZ 1 h, PTZ 6 h, PTZ 24 h, PTZ 48 h and PTZ 72 h respectively, after onset of status epilepticus (SE)]. Immunohistochemistry and immunofluorescence double-labeling were used to detect the temporal time change and distribution of p-DARPP-32 expression and to analyze the coexpression of DARPP-32 and p-DARPP-32 in rat brain after the onset of PTZ-induced generalized SE. The results showed that there was a temporal time change of p-DARPP-32 expression in rat brain after the onset of SE. The number of p-DARPP-32-positive cells increased significantly and reached the peaks at the ends of 1 hour and 6 hours after the onset of SE, but decreased at the end of 24 hours. The moderate to strong p-DARPP-32-immunopositive neurons were observed in cortex, hippocampus and striatum, and located in cell cytoplasm and cell nucleus. Further immunofluorescence double-labeling revealed that denser colocalization of p-DARPP-32 and DARPP-32 in the neurons existed in the area mentioned above. Therefore, PTZ-induced SE may cause phosphorylation of DARPP-32 in rat brain. The temporal time change and distribution of p-DARPP-32 suggest that phosphorylation of DARPP-32 may be involved in PTZ-induced epilepsy in rat brain including cortex, hippocampus and striatum, and p-DARPP-32 may play a central role in the onset of SE.
Animals ; Cerebral Cortex ; metabolism ; Corpus Striatum ; metabolism ; Dopamine and cAMP-Regulated Phosphoprotein 32 ; metabolism ; Hippocampus ; metabolism ; Male ; Neurons ; metabolism ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; chemically induced ; metabolism

Neuroprotective effect of scorpion venom on Parkinson's disease (PD) has already been reported. The present study was aimed to investigate whether scorpion venom heat resistant peptide (SVHRP) could attenuate ultrastructural abnormalities in mitochondria and oxidative stress in midbrain neurons of early-stage PD model. The early-stage PD model was established by injecting 6-hydroxydopamine (6-OHDA) (20 μg/3 μL normal saline with 0.1% ascorbic acid) into the striatum of Sprague Dawley (SD) rats unilaterally. The rats were intraperitoneally administered with SVHRP (0.05 mg/kg per day) or vehicle (saline) for 1 week. Two weeks after 6-OHDA treatment, the rats received behavior tests for validation of model. Three weeks after 6-OHDA injection, the immunoreactivity of dopaminergic neurons were detected by immunohistochemistry staining, and the ultrastructure of neuronal mitochondria in midbrain was observed by electron microscope. In the meantime, the activities of monoamine oxidase-B (MAO-B), superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the mitochondria of the midbrain neurons, as well as the inhibitory ability of hydroxyl free radical and the antioxidant ability in the serum, were measured by corresponding kits. The results showed that 6-OHDA reduced the optical density of dopaminergic neurons, induced damage of mitochondrial ultrastructure of midbrain neurons, decreased SOD activity, increased MAO-B activity and MDA content, and reduced the antioxidant ability of the serum. SVHRP significantly reversed the previous harmful effects of 6-OHDA in early-stage PD model. These findings indicate that SVHRP may contribute to neuroprotection by preventing biochemical and ultrastructure damage changes which occur during early-stage PD.
Animals ; Antioxidants ; metabolism ; Corpus Striatum ; Disease Models, Animal ; Dopaminergic Neurons ; drug effects ; Malondialdehyde ; metabolism ; Mesencephalon ; cytology ; Mitochondria ; metabolism ; ultrastructure ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; Oxidopamine ; Parkinson Disease ; drug therapy ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; pharmacology ; Superoxide Dismutase ; metabolism