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

The secondary motor cortex (M2) encodes choice-related information and plays an important role in cue-guided actions. M2 neurons innervate the dorsal striatum (DS), which also contributes to decision-making behavior, yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear. Using mice performing a visual Go/No-Go task, we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm (FA) rate to the reward-irrelevant No-Go stimulus. The choice signal of M2 neurons correlated with behavioral performance, and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS. By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs, we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus, and inactivating their early responses increased the FA rate. These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.
Mice ; Animals ; Motor Cortex ; Corpus Striatum/physiology* ; Neostriatum ; Neurons/physiology* ; Reaction Time

To study the effects of estrogen on the contents of dopamine (DA) and its metabolites in the amygdala (Amy) and striatum (Str) of rats, high performance liquid chromatography (HPLC) was used to measure the contents of DA and its metabolites in untreated ovariectomized (OVX) rats and OVX rats treated with estrogen. The contents of DA and its metabolites in Amy but not Str were significantly higher when the OVX rats were treated with a high dose of estradiol benzoate (EB). The turnover rate of DA in Amy of the OVX rats was lower than that of normal and EB-treated OVX rats. The turnover rate of DA in Amy was about twice as high as in the Str, while the content of DA in Amy was only one-sixth of that in the Str. The results obtained imply that serum concentration of estrogen is one of the important factors which affect the DA metabolism and content in the Amy of female rats, while the Str is not influenced by estrogen.
Amygdala ; metabolism ; Animals ; Corpus Striatum ; metabolism ; Dopamine ; metabolism ; Estrogens ; blood ; physiology ; Female ; Rats ; Rats, Wistar

Acoustic Stimulation ; Animals ; Corpus Striatum ; physiology ; Estrogens ; metabolism ; Estrus ; physiology ; Evoked Potentials, Auditory ; physiology ; Female ; Rats ; Rats, Sprague-Dawley

In this study, the effects of Radio Electric Asymmetric Conveyer (REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes (REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage in mice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TO-RGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism.
Animals ; Corpus Striatum ; pathology ; Electric Stimulation ; methods ; Inflammation ; pathology ; Male ; Mice ; Nerve Degeneration ; pathology ; Nerve Regeneration ; physiology ; Parkinsonian Disorders ; pathology

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by severe loss of substantia nigra dopamine (DA) neurons. The target region of substantia nigra DA neurons is the dorsal striatum. According to the classic model, activation of DA receptors on striatal medium spiny neurons (MSNs) modulates their intrinsic excitability. Activation of D1 receptors makes MSNs in the direct "Go" pathway more excitable, whereas activation of D2 receptors makes MSNs in the indirect "NoGo" pathway less excitable. Therefore increased DA increases the responsiveness of the Go pathway while decreases the responsiveness of the NoGo pathway. Both mechanisms increase motor output. Conversely, diminished DA will favor the inhibitory NoGo pathway. Therefore, DA has direct, "on-line" effect on motor performance. However, in addition to modulating the intrinsic excitability of MSNs "on-line", DA also modulates corticostriatal plasticity, therefore could potentially produce cumulative and long-lasting changes in corticostriatal throughput. Studies in my lab suggest that DA blockade leads to both direct motor performance impairment and D2 receptor dependent NoGo learning ("learned" motor inhibition) that gradually deteriorates motor performance. NoGo learning is experience dependent and task specific. It is different from blocked learning since NoGo learning impairs future performance even after DA is restored. More recent data from my lab suggest that NoGo learning in the absence of DA arises from increased LTP at the indirect pathway corticostriatal synapses and contributes significantly to PD-like motor symptoms. Our data and hypotheses suggest a novel therapeutic strategy for PD that targets directly signaling molecules for corticostriatal plasticity (e.g. the cAMP pathway and downstream signaling molecules) and prevents aberrant plasticity under conditions of DA denervation.
Corpus Striatum ; cytology ; Dopamine ; physiology ; Dopaminergic Neurons ; pathology ; Humans ; Neuronal Plasticity ; Parkinson Disease ; physiopathology ; Receptors, Dopamine D1 ; physiology ; Receptors, Dopamine D2 ; physiology ; Substantia Nigra ; pathology

Although the mammalian brain has long been thought to be entirely postmitotic, the recent discovery has confirmed an existence of neural stem or progenitor cells in various regions of the adult mammalian brain. Like embryonic stem cells, adult neural progenitor cells possess the capacity of self-renewal and differentiation potential for neurogenesis or gliogenesis. In addition to the subventricular zone and hippocampus where active cell division naturally occurs, adult neural progenitors with neurogenic potential exist in the striatum and the vicinity of dopaminergic neurons in the substantia nigra. Normally, progenitors in those regions proliferate at a low level, and most proliferated cells remain uncommitted. In response to the selective lesion of nigrostriatal dopaminergic pathway by the neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine, progenitors in the injured areas markedly increase their proliferation rate. Depending upon the magnitude and kinetics of the lesion, neurogenesis and gliogenesis were induced in the lesion sites at varying extents. A large number of growth and neurotrophic factors influence proliferation and/or differentiation of progenitor cells under normal and lesioned conditions. Some factors (epidermal and basic fibroblast growth factors and brain-derived neurotrophic factor) are facilitatory, while others (usually bone morphogenetic proteins) are inhibitory, for controlling division and fate of neuronal or glial progenitors. Expression of endogenous factors and their respective receptors in existing and newborn cells are also subject to be altered by the lesion. These genomic responses are considered to be important elements for the formation of a local molecular niche for a given phenotypic cell regeneration. Taken together, adult neural progenitor cells in the nigrostriatal dopaminergic system have the ability to respond to the lesion to repopulate missing cells. The regenerative neuro- or gliogenesis in situ can, at least in part, endogenously compensate injured neural elements, and achieve a self-repair of neurodegenerative disorders such as Parkinson's disease.
Adult Stem Cells ; physiology ; Animals ; Cell Differentiation ; physiology ; Corpus Striatum ; pathology ; physiopathology ; Humans ; Neurodegenerative Diseases ; physiopathology ; Neuronal Plasticity ; physiology ; Neurons ; cytology ; Parkinson Disease ; physiopathology ; Substantia Nigra ; pathology ; physiopathology

OBJECTIVETo study the dynamic characteristics of serotonin (5-HT), dopamine (DA) and their metabolin changes in brain during the development of exercise-induced central fatigue.

METHODSCoupling of microdialysis and capillary electrophoresis-laser induced fluorescence detection method were used to continuously monitored the changes of DA, tryptophan (Trp), tyrosine (Tyr), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in striatum extracellular fluid during the exhaustive exercise and recovery time.

RESULTSThe concentrations of Trp, 5-HT, 5-HIAA in striatum extracellular fluid had no remarkable changes in the early time of exercise (P < 0.05), while they significantly increased during the later time of exercise and whole recovery time (P < 0.05, P < 0.01). The concentrations of DA and Tyr significantly increased over basal level in the later exercise time, exhaust and recovery time (P < 0.05, P < 0.01). DA/5-HT significantly increased in the initial time of exercise (P < 0.05, P < 0.01), while decreased during the later exercise time, the nadir occurred at 15 minutes before rats exhausted. DA/5-HT slightly recovered back to basal level during the recovery time, and there was no significant difference during later exercise, exhausted and recovery time compared with basal level (P < 0.05).

CONCLUSIONThe changes of DA and 5-HT in striatum have phase characteristics. Both of them significantly increase during the development of exercise-induced fatigue. However, the 5-HT plays the dominant role in the dynamic changes of them.

Animals ; Corpus Striatum ; metabolism ; Dopamine ; metabolism ; Fatigue ; metabolism ; physiopathology ; Male ; Physical Conditioning, Animal ; physiology ; Physical Exertion ; physiology ; Rats ; Rats, Wistar ; Serotonin ; metabolism

The aim of the present study was to reveal the role of cortical-striatum postsynaptic dopamine D2 receptor (D2R) in improving motor behavioral dysfunction in Parkinson's disease (PD) mice by exercise. C57/BL6 male adult mice were randomly divided into control, PD and PD plus exercise groups. The mice were injected with 6-OHDA in striatum to establish a unilateral injury PD model. The exercise intervention program was uniform speed running (16 m/min, 40 min/d, 5 d per week for 4 weeks). Autonomic activity of mice was tested by open field test. Cortical-striatum synaptic transmission efficiency was assessed by peak amplitude of field excitatory postsynaptic potential (fEPSP) recorded from in vitro brain slides. Meanwhile, the effects of D2R agonist on autonomic activity and cortical-striatal synaptic transmission were observed. The results showed that, compared with PD group, PD plus exercise group exhibited significantly increased autonomic motor distance and proportion of fast-moving (P < 0.05), as well as decreased maximum amplitude of fEPSP under increasing stimulation intensity (0.75-3.00 pA) (P < 0.05) and slope of stimulus-response curve. Compared with PD mice without D2R agonist, the movement distance and rapid movement ratio of PD mice treated with D2R agonist were increased significantly (P < 0.05), whereas fEPSP peak amplitude (P < 0.05) and the slope of stimulus-response curve were decreased. These results indicate that either early exercise intervention or D2R agonist treatment can inhibit the abnormal increase of cortical-striatum synaptic transmission and improve the autonomic motor ability in PD mice, suggesting that the cortical-striatum synaptic D2R may be an important molecular target for exercise to improve the autonomic motor ability of PD mice.
Animals ; Corpus Striatum ; physiology ; Male ; Mice ; Mice, Inbred C57BL ; Oxidopamine ; Parkinson Disease ; physiopathology ; therapy ; Physical Conditioning, Animal ; Random Allocation ; Receptors, Dopamine D2 ; agonists ; physiology ; Synaptic Transmission

The transplantation of dopaminergic neurons in the brain has been attempted in experimental animals and humans as the new treatment modality of Parkinson's disease. Before the trial of dopaminergic neuronal transplantation in human, the authors proceeded with the animal experiment of fetal dopaminergic cell transplantation in a rat Parkinson's disease model. The aims of this experiment were to confirm the availability of fetal mesencephalic cells as the donor, to compare the viability of cells according to different cell manipulation methods, and to follow up the functional recovery in the transplanted Parkinson's disease model. As a result, the authors concluded that the simple enzyme digestion method had a better cell survival rate than the multiple enzyme digestion method. Also, the transplanted mesencephalic cells could not only survive in the host animal but also promote functional recovery.
Animal ; Corpus Striatum/*physiology ; Dopamine/*metabolism ; *Fetal Tissue Transplantation ; Male ; Mesencephalon/cytology/*embryology/metabolism ; Neurons/metabolism/*transplantation ; Parkinson Disease/*surgery ; Rats ; Rats, Sprague-Dawley ; Support, Non-U.S. Gov't