摘要:

AbstractRat neocortical neurons grown in dissociated cell culture were recorded with the whole‐cell patch‐clamp technique. Spontaneous inward currents were observed in cells that were held at a membrane potential of −80 mV in medium containing tetrodotoxin and Cd2+. These currents displayed amplitudes up to 140 pA and rise time of 1.8 ± 0.2 ms (mean ± SD, n = 15). They reversed near 0 mV and showed no voltage‐dependent frequency of occurrence. Hence, they were presumably due to spontaneous release of transmitter. The inward currents appeared around day 10 in culture and were detected up to 4 weeks. When cells of different ages were compared, the maximal probability of recording these inward events occurred at around 3 weeks in culture. The inward currents were not reduced by application of bicuculline methiodide which is a competitive antagonist of the GABAAreceptor, but were blocked by the broad‐spectrum glutamate receptor antagonist kynurenic acid. Moreover, spontaneous inward events were not affected by DL‐2‐aminophosphono‐valerate (NMDA receptor antagonist) but disappeared following application of the non‐NMDA receptors antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX). Our observations indicate that the inward currents represent miniature synaptic events that are primarily mediated by non‐NMDA excitatory amino acid receptor subtypes. Furthermore, our findings indicate that they develop over time and are not present in neurons that are grown in culture for less than

ISSN:0887-4476    

DOI:10.1002/syn.890180102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractElectrophysiological studies have suggested that inhibition of trigeminal motoneurons during mastication and the jaw‐opening reflex are mediated by last‐order interneurons (premotoneurons) utilizing GABA and glycine [Chandler et al. (1985), Brain Res., 325:181–186; Enomoto et al. (1987), Neurosci. Res., 4:396–412; Goldberg and Nakamura (1968), Experientia, 24:371–373; Kidokoro et al. (1968), J. Neurophysiol., 31:695–708; Nakamura et al. (1978), Exp. Neurol., 61:1–14]. In the present study we performed a series of double‐labeling experiments in guinea pigs to determine the location of neurons which contain GABA (gamma aminobutyric acid) or glycine that project to the trigeminal motor nucleus (Mo5). This was accomplished by performing immunohistochemical staining in combination with a retrograde tract tracing technique using colloidal gold bound to inactivated WGA‐HRP (wheat germ agglutin‐horseradish peroxidase) (gWGA‐HRP) as our retrograde tracer. Neurons which had a positive immunoreactivity to GABA or GAD (glutamic acid decarboxylase) and contained the retrograde marker were located in regions adjacent to the Mo5 such as the intertrigeminal, supratrigeminal, peritrigeminal and rostral portions of the parvocellular reticular formation alpha. Neurons which had a positive immunoreactivity to glycine and contained the retrograde marker were identified in the parvocellular reticular formation, the spinal trigeminal nucleus oralis, supratrigeminal and intertrigeminal regions. These data provide anatomical evidence for GABAergic and glycinergic projections to Mo5.

ISSN:0887-4476    

DOI:10.1002/syn.890180103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

Abstract3H‐glutamate (GLU) uptake was measured in hippocampal synaptosomes from rat brain. Addition of sodium nitroprusside (SNP) (Sodium nitroferricyanide), a generator of nitric oxide (NO), produced a time‐, temperature‐, and dose‐dependent inhibition of3H‐GLU uptake. The inhibition was due to changes in both Kd and Vmax of GLU uptake, and it was at least partially reversible upon washing. Addition of reduced hemoglobin (Hb), a substance that binds NO, prevented the SNP‐induced depression of uptake. Potassium ferricyanide, a compound similar to SNP, did not cause a reduction in3H‐GLU uptake. Utilization of another generator of NO, S‐nitroso‐N‐acetylpenicillamine (SNAP), produced similar results as did NO itself. Decreases in uptake were also observed in the striatum and cerebellum. Similar treatments did not consistently affect3H‐norepinephrine (NE) uptake, suggesting some selectivity in the NO effect. Thus, the observed inhibition of3H‐GLU uptake appears to be produced by NO, and it may represent a novel type of transynaptic retrograde regulation of transport. If found in vivo, inhibition of uptake activity could also be involved in the toxic effects of NO, the neurotoxicity of glutamate, and other potential neuronal changes associated with NO such as hippocampal long‐term potentiation. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in

ISSN:0887-4476    

DOI:10.1002/syn.890180104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

Abstract1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) causes marked depletion of dopamine (DA) levels and reduction in the activity of tyrosine hydroxylase (TH) in the nigrostriatal DA pathway. In the brain, the enzyme monoamine oxidase B converts MPTP to 1‐methyl‐4‐phenylpyridinium (MPP+) which enters DA terminals via DA uptake sites. Within the DA terminals, MPP+blocks the mitochondrial complex I and causes ATP depletion. This is thought to be the main cause of MPTP‐induced terminal degeneration. In addition, reactive oxygen species (ROS) generated after blockade of the complex I as well as those generated due to DA oxidation may participate in MPTP‐induced dopaminotoxicity. The present study sought to determine if a single injection of a large dose of MPTP generates ROS. We also sought to determine if these changes as well as changes in DA levels were correlated and age‐dependent. Toward that end, we have used C57/B6N male mice that were 22 days or 12 months old. These animals were injected with a single dose of MPTP (40 mg/kg, ip). Animals were sacrificed at various times after drug administration. MPTP produced no significant increase in ROS nor decreases in DA or HVA concentrations in the striatum of the younger mice. However, DOPAC concentrations were significantly decreased from 15–120 min after drug administration. In the older mice, MPTP caused significant increases in ROS from the beginning to the end of the study period. DA concentrations were decreased from 60 min onward. DOPAC concentrations were decreased significantly after 15–120 min while HVA concentrations were significantly increased after 60 and 120 min. These data demonstrate that in older mice, a single dose of MPTP can cause increases of ROS which were associated with subsequent decreases in DA concentrations. Younger mice were not similarly affected. These results suggest that MPTP induced neurotoxicity is age‐dependent and may be mediated by oxidative stress. ©1994 Wiley‐Lisa, Inc.This article is a US Government work and, as such, is in the public domain i

ISSN:0887-4476    

DOI:10.1002/syn.890180105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe effects of short‐ and long‐term cocaine exposure on the expression of the nuclear transcription factor genes, c‐fos and zif/268, as well as the opioid peptides, preprodynorphin (PPD) and preproenkephalin (PPE), in various regions of rat brain were evaluated by injecting i.p. saline or 10, 20, or 30 mg/kg cocaine HCl once daily for 1 or 10 days. In situ hybridization histochemistry was performed using 40mer oligonucleotides coding for c‐fos and zif/268, or 48mers coding for PPD and PPE, followed by quantitative image analysis. Behavioral ratings demonstrated that on day 1 cocaine‐induced activity increased in a dose‐dependent manner. Statistical analysis revealed that repeated administration of cocaine for 10 days resulted in an augmentation of the behavioral response elicited by acute exposure to cocaine. Image analysis of film autoradiograms demonstrated that 1 h after a single injection of cocaine, the expression of c‐fos and zif/268, but not PPD or PPE in the dorsal striatum and cortex, was enhanced in a dose‐dependent manner as compared to that in saline controls. In contrast, administration of 30, but not 10 or 20, mg/kg cocaine for 10 days increased the expression of PPD but not PPE, mRNA and downregulated that of c‐fos and zif/268 as compared to acute cocaine. These data indicate that repeated, high dose cocaine administration induces an increased PPD but not PPE genomic response and that the expression of c‐fos and zif/268 is dissociable from that of PPD. ©

ISSN:0887-4476    

DOI:10.1002/syn.890180106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractImmunocytochemistry with an antibody‐directed tyrosine hydroxylase (TH) was combined with electron microscopy and serial‐section analysis to examine the synaptic organization of the catecholaminergic projection to the stratum griseum superfciale (SGS) of the hamster's superior colliculus (SC). A total of 250 TH‐immunoreactive profiles within SGS were examined. Of these, 114 (45.6%) made synaptic contacts; 81 (71.1%) were axodendritic, and the remainder (33, 28.9%) were axo‐axonic. Serial‐section analysis was employed to evaluate the presence or absence of synaptic contacts for 26 profiles. Overall, 19 (73.1%) of the profiles followed through serial sections exhibited synaptic contacts. Double staining of single sections with antibodies directed against TH and dopamine‐ß‐hydroxylase (DßH) and examination in the light microscope indicated that virtually all TH‐positive fibers also contained DßH. This indicated that the fibers examined at the electron microscopic level were noradrenergic rather than dopaminergic. These results suggest that norepinephrine may have both pre‐ and postsynaptic actions in the hamster's SC and that at least some of these effects are mediated by c

ISSN:0887-4476    

DOI:10.1002/syn.890180107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn addition to numerous GABA‐ergic efferent neurons, the striatum contains a subpopulation of fast‐firing GABA‐ergic interneurons characterized by the presence of immunoreactivity for the calcium‐binding protein, parvalbumin. Doublelabel in situ hybridization with digoxigenin‐ and radiolabelled cRNA probes was performed on striatal: sections of adult rats to identify mRNAs expressed by striatal GABAergic interneurons. In the dorsolateral striatum, only parvalbumin mRNA‐positive neurons expressed the mRNA encoding the potassium channel Kv3.1, a member of the Shaw family of potassium channels with rapid activation and inactivation kinetics, usually found in fast‐firing neurons such as the basket cells of the hippocampus. Colocalization of the parvalbumin and Kv3.1 proteins was confirmed by double‐label immunohistochemistry. Parvalbumin mRNA‐positive neurons expressed very high levels of the mRNA encoding glutamic acid decarboxylase (Mr 67,000: GAD67) in the dorsolateral striatum. A smaller proportion of double‐labelled neurons was found in the ventrolateral striatum. A small number of densely labelled neurons for GAD67 mRNA also expressed the mRNA encoding the dopamine D2 receptor, but none expressed detectable levels of the dopamine D1 receptor mRNA. This indicates major differences in the expression of dopamine receptor mRNA in a majority of GABA‐ergic interneurons vs. GABA‐ergic efferent neurons of the striatum. The results suggest that distinct molecular characteristics are associated with the distinct electrophysiological properties of striatal GABA‐ergic neuron

ISSN:0887-4476    

DOI:10.1002/syn.890180108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe effect of long‐term (6–19 weeks) 6‐hydroxydopamine‐induced (6‐OHDA) lesions of midbrain dopamine cells on dopamine D1‐like agonist‐induced changes in the excitability of rat striatal neurons was investigated in vitro using tissue slices and intracellular recording techniques. Fenoldopam and (±)‐SKF 38393 predominantly decreased excitability in control preparations including striatal neurons located contralateral to 6‐OHDA injection sites and neurons obtained from rats receiving sham injections or no treatment. Fenoldopam also inhibited neurons ipsilateral to lesions of midbrain dopamine cells. (±)‐SKF 33393, unlike fenoldopam, produced predominantly increases in the excitability of ipsilateral striatal neurons. Superfusion of the D1receptor antagonist, SCH 23390, blocked fenoldopam‐induced decreases in excitability but not the (±)‐SKF 38393‐induced excitation of neurons ipsilateral to the lesion. Sequential application of fenoldopam and quinpirole, a D2/D3receptor agonist, produced responses to both drugs in a majority of neurons. The results demonstrate that inhibitory responses to fenoldopam are mediated by D1receptors, while excitatory effects of (±)‐SKF 38393 in the striatum ipsilateral to the lesion are apparently not dependent on D1receptor activation. These findings also suggest that dopamine D1and D2/D3 receptors are able to concurrently influence the excitability of striatal neurons in the dopamine deafferentated striatum. Similar regulation of striatal neurons in vivo may contribute to dopaminergic regulation of basal ganglia output and the ability of dopaminomimetic agents to ameliorate symptoms of dopaminergic deficiency in Parkinson's disease. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public doma

ISSN:0887-4476    

DOI:10.1002/syn.890180109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890180101

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY