Caudate unit responses to nigral stimuli: evidence for a possible nigro-neostriatal pathway

Electrical stimulation of the Substantia nigra evokes depressant and facilitatory responses from individually recorded caudate nucleus neurons. These effects resemble those elicited from caudate cells by microiontophoretic ejections of dopamine. Since histochemical evidence suggests that dopamine-containing fibers link the substantia nigra with the caudate, this pathway may mediate the changes in caudate spike rates produced by nigral stimuli.     

Alterations in L-glutamate binding in Alzheimer's and Huntington's diseases

Brain sections from patients who had died with senile dementia of the Alzheimer's type (SDAT), Huntington's disease (HD), or no neurologic disease were studied by autoradiography to measure sodium-independent L-[3H]glutamate binding. In brain sections from SDAT patients, glutamate binding was normal in the caudate, putamen, and claustrum but was lower than normal in the cortex. The decreased cortical binding represented a reduction in numbers of binding sites, not a change in binding affinity, and appeared to be the result of a specific decrease in numbers of the low-affinity quisqualate binding site. No significant changes in cortical binding of other ligands were observed. In brains from Huntington's disease patients, glutamate binding was lower in the caudate and putamen than in the same regions of brains from control and SDAT patients but was normal in the cortex. It is possible that development of positron-emitting probes for glutamate receptors may permit diagnosis of SDAT in vivo by means of positron emission tomographic scanning.     

Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity

Exposure of cultures of cortical cells from mouse to either of the endogenous excitatory neurotoxins quinolinate or glutamate resulted in widespread neuronal destruction; but only in the cultures exposed to quinolinate, an N-methyl-D-aspartate agonist, was there a striking preservation of the subpopulation of neurons containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). Further investigation revealed that neurons containing NADPH-d were also resistant to the toxicity of N-methyl-D-aspartate itself but were selectively vulnerable to the toxicity of either kainate or quisqualate. Thus, neurons containing NADPH-d may have an unusual distribution of receptors for excitatory amino acids, with a relative lack of N-methyl-D-aspartate receptors and a relative preponderance of kainate or quisqualate receptors. Since selective sparing of neurons containing NADPH-d is a hallmark of Huntington's disease, the results support the hypothesis that the disease may be caused by excess exposure to quinolinate or some other endogenous N-methyl-D-aspartate agonist.     

Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease

Golgi impregnations of neostriatum from deceased Huntington's disease patients and controls were examined. In all cases of Huntington's disease the morphology of dendrites of medium-sized spiny neurons was markedly altered by the appearance of recurved endings and appendages, a decrease or increase in the density of spines, and abnormalities in the size and shape of spines. Pathological changes were rarely observed in medium-sized and large aspiny neostriatal neurons. The findings provide evidence for simultaneous degeneration and growth of spiny neurons in Huntington's disease and support the view that a specific population of neostriatal neurons is selectively involved in its pathogenesis.     

Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system

In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.     

Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics

In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density.     

Delayed transneuronal death of substantia nigra neurons prevented by gamma-aminobutyric acid agonist

In an investigation of the mechanism by which brain lesions result in delayed degeneration of neurons remote from the site of injury, neurons within the caudate nucleus of rats were destroyed by local injection of the excitotoxin ibotenic acid. Treatment resulted in the rapid degeneration of the striatonigral pathway including projections containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and delayed transneuronal death of neurons in the substantia nigra pars reticulata. The distribution of nigral cell loss corresponded to the loss of GABAergic terminals. Neuronal death was prevented by long-term intraventricular infusion of the GABA agonist muscimol. Delayed transneuronal degeneration may be produced by neuronal disinhibition consequent to loss of inhibitory inputs. Replacement of inhibitory transmitters by suitable drugs may prevent some forms of delayed neuronal death.     

Amyloid protein precursor messenger RNAs: differential expression in Alzheimer's disease

In situ hybridization was used to assess total amyloid protein precursor (APP) messenger RNA and the subset of APP mRNA containing the Kunitz protease inhibitor (KPI) insert in 11 Alzheimer's disease (AD) and 7 control brains. In AD, a significant twofold increase was observed in total APP mRNA in nucleus basalis and locus ceruleus neurons but not in hippocampal subicular neurons, neurons of the basis pontis, or occipital cortical neurons. The increase in total APP mRNA in locus ceruleus and nucleus basalis neurons was due exclusively to an increase in APP mRNA lacking the KPI domain. These findings suggest that increased production of APP lacking the KPI domain in nucleus basalis and locus ceruleus neurons may play an important role in the deposition of cerebral amyloid that occurs in AD.     

Mental symptoms in Huntington's disease and a possible primary aminergic neuron lesion

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.     

兔脑和脊髓内开胃素A免疫阳性神经元和神经纤维的分布

采用免疫组织化学法研究了10只青紫蓝兔脑内开胃素（Orexin） A免疫阳性神经元和神经纤维的分布。结果显示,Orexin A免疫阳性神经元分布于下丘脑的视上核、室旁核、背内侧核、穹隆周核、外侧区、前区和后区以及底丘脑的未定带。Orexin A免疫阳性神经纤维广泛分布于中枢神经系统内,在端脑分布于大脑皮质、尾状核、隔核和杏仁核;在间脑分布于丘脑、下丘脑、上丘脑和垂体;在中脑分布于中央灰质、前丘、后丘、黑质、网状结构和中缝核;在脑桥分布于蓝斑、网状结构和中缝核;在延髓分布于极后区、孤束核和迷走神经背侧运动核;在小脑和脊髓也有分布。     

Cyclic adenosine monophosphate: selective increase in caudate nucleus after administration of L-dopa

Treatment with the dopamine precursor L-dopa produced a significant accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in the caudate nucleus of the rat. In contrast, there was no change in the amount of cyclic AMP in the cerebellum. Accumulation of cyclic AMP in the caudate nucleus after administration of L-dopa was prevented by prior treatment with the decarboxylase inhibitor RO 4-4602. These observations and those in other laboratories support the assumption that dopamine formed from L-dopa selectively activates striatal adenylate cyclase. The in vivo activation of adenylate cyclase after treatment with L-dopa may be a useful model for studying neurological and psychiatric disorders that are thought to involve the dopaminergic system of the brain.     

Long-term neuropathological and neurochemical effects of nucleus basalis lesions in the rat

The long-term effects of excitotoxic lesions in the nucleus basalis magnocellularis of the rat were found to mimic several neuropathological and chemical changes associated with Alzheimer's disease. Neuritic plaque-like structures, neurofibrillary changes, and neuronal atrophy or loss were observed in the frontoparietal cortex, hippocampus, amygdala, and entorhinal cortex 14 months after the lesions were made. Cholinergic markers in neocortex were reduced, while catecholamine and indoleamine metabolism was largely unaffected at this time. Bilateral lesions of the nucleus basalis magnocellularis increased somatostatin and neuropeptide Y in the cortex of the rat by at least 138 and 284 percent, respectively, suggesting a functional interaction between cholinergic and peptidergic neurons that may differ from that in Alzheimer's disease.     

Subthalamic GAD gene therapy in a Parkinson's disease rat model

The motor abnormalities of Parkinson's disease (PD) are caused by alterations in basal ganglia network activity, including disinhibition of the subthalamic nucleus (STN), and excessive activity of the major output nuclei. Using adeno-associated viral vector-mediated somatic cell gene transfer, we expressed glutamic acid decarboxylase (GAD), the enzyme that catalyzes synthesis of the neurotransmitter GABA, in excitatory glutamatergic neurons of the STN in rats. The transduced neurons, when driven by electrical stimulation, produced mixed inhibitory responses associated with GABA release. This phenotypic shift resulted in strong neuroprotection of nigral dopamine neurons and rescue of the parkinsonian behavioral phenotype. This strategy suggests that there is plasticity between excitatory and inhibitory neurotransmission in the mammalian brain that could be exploited for therapeutic benefit.     

Reversal of experimental parkinsonism by lesions of the subthalamic nucleus

Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.     

神经元在动物下丘脑中分布的研究进展

对近年来研究较多的神经元在动物下丘脑各个神经核中的分布情况作了介绍,指出神经元在下丘脑各个神经核均有分布,甚至有几种神经元同时分布在某些神经核中,视上核(SON)、室旁核(PVN)及弓状核(ARC)是多种神经元集中分布的主要神经核,为进一步研究下丘脑的生理功能提供了形态学资料。     

Cerebral Heterostimulation in a Monkey Colony

In an established colony a subordinate monkey repeatedly pr essed a lever which stimulated the caudate nucleus of the boss monkey by radio and inhibited his aggressive behavior. In other experiments, timed stimulations of the posteroventral nucleus of the thalamus of the boss monkey, paired with a tone, increased his aggressiveness and established conditioned escape responses of the whole group. Both types of experiments may be useful in neurophysiological and pharmacological investigations.     

( 3 H)lysergic acid diethylamide: cellular autoradiographic localization in rat brain

Intravenous administration of [(3)H]lysergic acid diethylamide(LSD) to rats resulted in accumulation of the drug in the brain within 15 minutes. Autoradiographic methods were used to differentiate free and bound [(3)H]LSD in brain tissue.Free [(3)H]LSD was generally distributed in the pituitary and pineal glands, cerebellum, hippocampus,and choroid plexus.Bound [(3)H]LSD was localized in neurons of the cortex, caudate nucleus, midbrain, and medulla,as well as in choroid plexus epithelium.     

Dopamine: release from the brain in vivo by amantadine

After dopamine stores in the caudate nucleus of cats were labeled with [(3)H]dopamine, the ventricular system was perfused with artificial cerebrospinal fluid. The addition of amantadine to the perfusing fluid caused a doserelated increase in the concentrations of [(3)H]dopamine appearing in the perfusion effluent. Subthreshold concentrations of amantadine also enhanced the efflux of [(3)H]dopamine induced by electrical stimulation of the caudate nucleus.     

Long-term potentiation in the motor cortex

Long-term potentiation (LTP) is a model for learning and memory processes. Tetanic stimulation of the sensory cortex produces LTP in motor cortical neurons, whereas tetanization of the ventrolateral nucleus of the thalamus, which also projects to the motor cortex, does not. However, after simultaneous high-frequency stimulation of both the sensory cortex and the ventrolateral nucleus of the thalamus, LTP of thalamic input to motor cortical neurons is induced. This associative LTP occurs only in neurons in the superficial layers of the motor cortex that receive monosynaptic input from both the sensory cortex and the ventrolateral nucleus of the thalamus. Associative LTP in the motor cortex may constitute a basis for the retention of motor skills.