The basal ganglia, a group of nuclei, are associated with a variety of functions, including motor control. The striatum, which is the major input station of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. The striatum is made up 96% of medium spiny neurons which are GABAergic cells. GABAergic cells are known to contain DA receptors which divide into two main branches- the D1 receptor (D1R)-expressing direct pathway and the D2 receptor (D2R)-expressing indirect pathway. The role of these two efferent pathways has not been clear in control of motor behaviors. To establish the influence of the different DA subtypes on GABAergic systems in the striatum, D1 selective receptor agonist (SKF 38393) and D2 selective receptor agonist (Quinpirole) were administered to mice. SKF 38393 and quinpirole were administered intraperitoneally in a volume of 0, 1, 5, 10 (mg/kg) and motor activity was assessed for 60 min immediately after the injection of DA agonists. Mice were sacrificed after behavioral test and the striatum in the brain were dissected for analysis of GABA level with HPLC. Both SKF 38393 and quinpirole dose-dependently increased locomotor activity but, GABA level in the striatum was clearly different in two agonists. These findings provide insight into the selective contributions of the direct and indirect pathways to striatal GABAergic motor behaviors.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Animals ; Basal Ganglia ; Brain ; Chromatography, High Pressure Liquid ; Efferent Pathways ; gamma-Aminobutyric Acid ; Mice ; Motor Activity ; Neurons ; Quinpirole ; Substantia Nigra

OBJECTIVETo trace the segmental distribution of somatic sensory neurons of the skin and dorsal nerve in the rabbitś penis.

METHODSThe experiment was performed on 8 adult male rabbits with the nerve tracing method of retrograde axonal transport of horseradish peroxidase (HRP), which was injected into the dermis around the penis and the dorsal nerve of the penis. The rabbits were sacrificed five days later to harvest the spinal cord segments and the dorsal root ganglia of lumbosacral segments for histological study.

RESULTSThe HRP tracing showed that a number of labeled HRP positive neurons appeared in spinal ganglia (S2 - S4) in all the rabbits, and distributed segmentally. The counts of the positive neurons different segments were: S2 (215.0 +/- 10.2) , S3 (242.2 +/- 8.3) and S4 (109.7 +/- 8.4) respectively, with statistically significant difference between the two groups.

CONCLUSIONThe rabbit's sensory nerve fibers in both the skin and the dorsal nerve of the penis are rooted in the S2-S4 segments of spinal ganglia, which distribute regularly.

Animals ; Anterior Horn Cells ; anatomy & histology ; Biomarkers ; Male ; Neurons, Afferent ; Neurons, Efferent ; Penis ; innervation ; Rabbits ; Random Allocation ; Skin ; innervation

Recently, motor evoked potential(MEP) using cortical surface of transcranial stimulation have been used to monitor the integrity of motor pathways and map motor cortex in human and animal. The primary concept using motor evoked potentials(MEPs) for test of motor pathways was based on the assumtion that pyramidal neurons in the motor cortex are activated by electrical stimulation applied on the cerebral cortex and synchronized compound action potentials are conducted mainly along the corticospinal tracts in the spinal cord. However, the origins and the descending pathways of these MEPs in small animals may be different from those of potentials evoked by intracortical microstimulation because of current spread. Our previous study revealed that the origns of the MEPs in rats differed from those previously believed and may be reticular nuclei. To further clarify those results and localize the intraspinal pathways conduction MEPs, consecutive vertical and/or horizontal sections of the spinal cord were performed at T9 cord level in twelve rats. MEPs were recorded at T2/3 and L2/3 before and after each section and sequential alterations of MEPs were observed. In six rats, the stimulation was alternated between the right and left cortex and the lateralities of conduction pathways were compared. All six cases showed no differences of MEPs and pattern of wave abolition after each section between right and left brain stimulation. The alteration of MEPs after each consecutive section was categorized by analyzing latency shift, amplitude change, and disappearance of waves. We divided a cross section of T9 spinal cord into forty-six squares. If one of the categorized changes occurrd after cutting an area, the appropriate score was given for the area since more change of waves meant more significant contribution of the cut area to conduction of MEPs. The score of twelev rats were summed in each forty-six spots and map showing the distribution of MEPs was constructed. The map revealed that MEPs were conducted along the wide area of ventral and lateral funiculus of the spinal cord but mainly along the medial portion of the ventral funiculus of the spinal cord but mainly along the medial portion of the ventral funiculus and ventral portion of the larteral funiculus through which reticulospinal and vestibulospinal tracts pass. No conduction of MEPs along the corticospinal tracts was confirmed. This finding supports the result of our previous study. However, this extrapyramidal MEP conducted along ventral spinal cord in addition to somatosensory evoked potential(SSEP) which is conducted along posterior funiculus can be useful to monitor the integrity of the whole spinal cord. Moreover, the extrapyramidal MEP can be more useful than pyramidal MEP in rats because the reticular formation plays a more important role in motor function and pyramidal tract is located in posterior funiculus.
Action Potentials ; Animals ; Brain ; Cerebral Cortex ; Efferent Pathways ; Electric Stimulation ; Evoked Potentials, Motor* ; Extrapyramidal Tracts ; Humans ; Motor Cortex ; Neurons ; Pyramidal Tracts ; Rats* ; Reticular Formation ; Spinal Cord

Motor evoked potential(MEP) produced by cortical surface or transcranial stimulation has evolved as a new clinical and experimental tool to monitor the integrity of motor pathways and to map motor cortex. Clinical assessment of motor system using MEP has further advanced with recent development of the magnetic stimulator. The primary concept using MEPs for test of motor pathways was based on the assumption that pyramidal neurons in the motor cortex are activated by electrical stimulation applied on the cerebral cortex and synchronized compound action potentials are conducted mainly along the corticospinal tracts in the spinal cord. However,recent studies indicated that the origins of the Meps in non primates may differ from those previously believed. In order to use MEPs as a clinical or experimental tool, it is essential to clarify the origin of MEPs. Therefore, goals of this study were : (1) to investigate the origin of MEPs, and (2) to design the most reliable but simple method to evoke and monitor MEPs. In a total of fifteen rats, MEPs were produced by cortex to cortex stimulation and were monitored using a pair of epidural electrodes. Using varying stimulus intensities, the amplitudes and latencies of MEPs were statistically analyzed. The latencies and amplitudes of the MEPs in these animals showed surprisingly large standard deviations, which were partially resulted in these animals showed surprisingly large standard deviations, which were partially resulted from convergence of neighboring waves during high stimulation intensities. Wave forms of MEPs were also varied greatly depending on the position of recording electordes. At low stimulus intensities, most consisten MEPs were obtained when the stimulating electrodes were placed on the hard palate and the temporal muscle, not on the motor cortex. This observation indicates that the primary source of MEPs is not the motor cortex in the rat. When the potentials generated by direct stimulation of motor cortex and those generated by reticular nuclei were monitored epidurally in the same preparation using the same electrodes, these potentials generated by different sources actually identical in their latencies and wave forms. However, the threshold stimulus intensities evoking these potentials were quite different in the two metholds. The threshold was much lower to evoke potentails by reticular nuclei stimulation. It suggests that MEPs are geneated by the reticular nuclei or brain structure located in the brain stem. The observation that the motor cortex play no major roles in generating MEPs was confirmed by sequential sections of neural axis from the motor cortex to brain stem in three rats. All these findings suggested that neither direct motor cortex stimulation not transcranial stimulation did evoke MEPs originating from the motor cortex in rat. These stimulating methods activate reticular nuclei by stimulus current spread to the brain stem. Since the reticular formation plays an important role in motor function in rats, MEP originated from reticular nucleus can be an important testing of the motor function in rats. Moreover, transcranial stimulation of the brain is technically easy. This technique producing MEPs originated from reticular nucleus can be useful to monitor the integrity of motor pathways.
Action Potentials ; Animals ; Axis, Cervical Vertebra ; Brain ; Brain Stem ; Cerebral Cortex ; Efferent Pathways ; Electric Stimulation ; Electrodes ; Evoked Potentials, Motor* ; Extrapyramidal Tracts ; Motor Cortex ; Neurons ; Palate, Hard ; Primates ; Pyramidal Tracts ; Rats* ; Reticular Formation ; Spinal Cord ; Temporal Muscle

Efferent neurons release acetylcholine to inhibit sensory hair cells of the inner ear. The alpha9alpha10 nicotinic acetylcholine receptor (nAChR) mediates efferent inhibition of hair cell function within the auditory sensory organ. Gating of the nAChR triggers inward calcium current, and leads to activation of calcium dependent, small-conductance potassium (SK) potassium channels to hyperpolarize the hair cell. Through SK channels, large potassium outflow occurred, and outer hair cell was hyperpolarized. Thus, amplification of sound and sensitivity of hearing was reduced or modulated by efferent inhibition. In efferent system, main calcium providers to SK channel are nAChR and synaptic cistern, which contribution to efferent inhibition is different between avian and mammalian species. Calcium permeation is more effective in nAChRs of mammalian cochlea than avian cochlea, and mammalian calcium permeability of nAChRs is about 3 times more than avian hair cell. Thus, nAChRs is a main component of efferent inhibition in mammalian cochlear hair cell system.
Acetylcholine ; Calcium ; Cochlea ; Ear, Inner ; Hair ; Hearing ; Neurons, Efferent ; Permeability ; Potassium ; Potassium Channels ; Receptors, Nicotinic

OBJECTIVETo investigate the efferent pathway from the dorsal raphe nucleus to the inner ear.

METHODSEleven adult cats weighing 2.0 - 3.0 kg were used. The animals had no middle-ear disease and their auricle reflex was sensitive to sound. They were divided into experimental group (8 cats) and control group (3 cases). The fluorescent tracer cholera toxin subunit-B (CTB) was injected into cat cochlea and the CTB-labelled neurons of dorsal raphe nucleus (DRN) were identified using an immunofluorescence technique after a survival period of 7 days. For studying other fluorescence labelling, the sections containing CTB-labelled neurons were divided into four groups and incubated in antisera directed against tyrosine hydroxylase (TH), serotonin (5-HT), gamma-aminobutyric acid (GABA) and dopamine B-hydroxylase (DBH), respectively. Single-and double-labelled neurons were identified from the DRN.

RESULTS(1) A subpopulation of dorsal raphe nucleus (DRN) neurons were intensely labelled with CTB and these CTB-labelled neurons were densely distributed in a dorsomedial part of the DRN; (2) Four immunolabelling, TH, 5-HT, GABA and DBH were presented throughout the DRN. Of the total population of CTB-labelled neurons, 100% were TH-labelled neurons (double labelling) and no double-stained neuron with 5-HT, GABA and DBH was observed in the DRN.

CONCLUSIONSThere was a projection from DRN to the inner ear and this pathway might be a dopaminergic projection.

Animals ; Cats ; Ear, Inner ; innervation ; metabolism ; Efferent Pathways ; Neurons ; metabolism ; physiology ; Raphe Nuclei ; metabolism ; physiology

Descending activation pathways in spinal cord are essential for inducing and modulating autokinesis, but whether the effects of general anesthetic agents on the descending pathways are involved in initiation of skeletal muscle relaxation or not, as well as the underlying mechanisms on excitatory amino acid receptors still remain unclear. In order to explore the mechanisms underlying etomidate's effects on descending activation of spinal cord motoneurons (MNs), the conventional intracellular recording techniques in MNs of spinal cord slices isolated from neonatal rats (7-14 days old) were performed to observe and analyze the actions of etomidate on excitatory postsynaptic potential (EPSP) elicited by electrical stimulation of the ipsilateral ventrolateral funiculus (VLF), which was named VLF-EPSP. Etomidate at 0.3, 3.0 (correspond to clinical concentration) and 30.0 µmol/L were in turn perfused to MN with steadily recorded VLF-EPSPs. At low concentration (0.3 µmol/L), etomidate increased duration, area under curve and/or half-width of VLF-EPSP and N-methyl-D-aspartate (NMDA) receptor-mediated VLF-EPSP component (all P < 0.05), as well as amplitude, area under curve and half-width of non-NMDA receptor-mediated VLF-EPSP component (all P < 0.05), or decreased amplitude and area under curve of VLF-EPSP, its NMDA receptor component, and non-NMDA receptor component (all P < 0.05). However, at 3.0 and 30.0 µmol/L, it was only observed that etomidate exerted inhibitory effects on amplitude and/or duration and/or area under curve of VLF-EPSP (P < 0.05 or P < 0.01) with concentration- and time-dependent properties. Moreover, NMDA receptor-mediated VLF-EPSP component was more sensitive to etomidate at ≥ 3.0 µmol/L than non-NMDA receptor-mediated VLF-EPSP component did. As a conclusion, etomidate, at different concentrations, exerts differential effects on VLF-EPSP and glutamate receptors mediating the synaptic transmission of descending activation of MNs in neonatal rat spinal cord in vitro.
Anesthetics, Intravenous ; pharmacology ; Animals ; Animals, Newborn ; Efferent Pathways ; physiology ; Electric Stimulation ; Etomidate ; pharmacology ; Excitatory Postsynaptic Potentials ; drug effects ; physiology ; Female ; In Vitro Techniques ; Male ; Motor Neurons ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; drug effects ; physiology ; Spinal Cord ; physiology

BACKGROUND AND OBJECTIVES: It has been known that the motility of the outer hair cell controls the physiological characteristics of the organ of Corti. Motility can be divided into two different types: fast and slow motility. Slow motility can be induced by high concentration of KCl and increase of intracellular Ca2+ concentration. In this study, authors aimed to define the effect of acetylcholine, one of the efferent neurotransmitters, on the slow motility of the outer hair cells of guinea pig. MATERIALS AND METHOD: Outer hair cells were isolated from guinea pigs by enzymatic and mechanical dissociation. The length of the hair cells was recorded by CCD camera equipped on an inverted microscope. Slow motility was induced by 10 (micro)M of ionomycin and 150 mM of KCl. Carbamylcholine (1 mM), a non-hydrolyzable derivative of acetylcholine, was used to observe the effect of acetylcholine and choline chloride (1 mM) was used as control. RESULTS: The length of outer hair cell was decreased after adding 150 mM of KCl and increased after adding 10 (micro)M of ionomycin. Stimulation of carbamylcholine (1 mM) did not induce the length change of the outer hair cells. Preincubation of 1 mM of carbamylcholine also did not affect the length change induced by ionomycin or KCl in outer hair cells. CONCLUSION: We could suggest that carbamylcholine does not have an effect on the slow motility of outer hair cell induced by the change of osmotic pressure which was elicited by high potassium, or intracellular Ca2+ increase.
Acetylcholine ; Animals ; Calcium* ; Carbachol ; Choline ; Guinea Pigs ; Hair* ; Ionomycin ; Neurons, Efferent ; Neurotransmitter Agents ; Organ of Corti ; Osmotic Pressure ; Potassium Chloride ; Potassium*

OBJECTIVE: To investigate the distribution and morphology of olivocochlear neurons of superior olivary complex in cats. METHODS: Eight adult cats were divided into 2 groups randomly. Cholera toxin B subunit was injected to the left cochlea and fluoro-gold was injected to the right cochlea in the experimental group (n=5). Saline was injected to bilateral cochlea in the control group (n=3). Brainstem tissue was sectioned serially. All of the sections were immunohistochemically treated with ABC and stained with DAB, and then the labelled olivocochlear neurons were observed. RESULTS: The labelled olivocochlear neurons in the experimental group were 2 518 in total. Of them, the number of lateral olivocochlear (LOC) neurons was 1 738 (69.0%), mainly located in the middle of the pons, predominantly projected ipsilaterally. The total of medial olivocochlear (MOC) neurons was 780 (31%), mainly located in dorsomedial periolivary nucleus, medial nucleus of the trapezoid body and ventral nucleus of the trapezoid body, mainly distributed in the rostral extent of the pons, predominantly projected contralaterally. CONCLUSION In the distribution of olivocochlear neurons in cats, LOC neurons mainly project to the ipsilateral. While the projection of MOC neurons is predominantly contralateral, the distribution of MOC neurons is more adjacent to the rostral extent of the pons than LOC neurons.
Animals ; Auditory Pathways ; cytology ; Brain Stem ; cytology ; Cats ; Cholera Toxin ; administration & dosage ; Cochlea ; innervation ; Cochlear Nucleus ; cytology ; Female ; Injections ; Male ; Neurons ; cytology ; Neurons, Efferent ; cytology ; Olivary Nucleus ; cytology

BACKGROUND: Dyskinesia is a common side effect complicating long-term levodopa therapy for Parkinson's disease. However, the pathogenesis of dyskinesia has not been completely understood. In recent animal studies, it has been reported that a NMDA (N-methyl-D-aspartate) antagonist reduced levodopa-induced dyskinesia. These findings suggest that the hyperfunction of NMDA receptors on striatal efferent neurons contributed to the pathogenesis of dyskinesia. Amantadine has also been recently shown to antagonize central NMDA receptors. In the present study, we observed amantadine efficacy in levodopa-induced dyskinesia in parkinsonian patients. METHODS:Twenty-two parkinsonian patients with levodopa-induced dyskinesia participated in a placebo-controlled, cross-over study. We prescribed 100 mg amantadine daily as a starting dose, which was built up every four days and titrated up to 400 mg a day. After two weeks of a wash-out period, a placebo was given with the same schedule. The doses of levodopa and other antiparkinsonian drugs were unchanged during this period. We assessed the duration and disability of dyskinesia (UPDRS part IV, item 32 and 33) based on diary and interview. RESULTS: Amantadine was superior to placebo in reducing the duration of dyskinesia in 9 patients (42.9%) and the disability of dyskinesia in 11 patients (52.4%). The reduction of the duration and disability of dyskinesia was correlated with the dose of amantadine. CONCLUSIONS These findings suggest that amantadine can improve levodopa induced dyskinesia and supports the view that the hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa induced dyskinesia.
Amantadine* ; Animals ; Appointments and Schedules ; Cross-Over Studies ; Dyskinesias* ; Humans ; Levodopa ; N-Methylaspartate ; Neurons, Efferent ; Parkinson Disease ; Receptors, N-Methyl-D-Aspartate