摘要:

AbstractNeuronal population activity was investigated by computer simulation of a network model based on the neostriatum. Three network topologies were studied, based on different assumptions about the synaptic connectivity among medium spiny neurons. In all networks neurons were interconnected by inhibitory synapses. The connectivity was either symmetric, in which case all connections between cells were reciprocal and equal in strength; or asymmetric. Simulations showed that networks with symmetric connectivity receiving randomly distributed afferent excitation produced stationary spatial activity patterns. In contrast, asymmetric connectivity in homogeneous networks produced slow travelling‐wave activity across the network. We suggest that the shape of the medium spiny neurons is an important determinant of synaptic connectivity and that changes in the shape of these neurons caused by Huntington's disease would result in asymmetric connectivity. Slow travelling‐wave activity produced by asymmetric connectivity in the neostriatum could explain some aspects of the choreic movement and some electromyographic features seen in Huntington's patients. © 1995 Wiley‐Lis

ISSN:0887-4476    

DOI:10.1002/syn.890200402

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

年代:1995

数据来源: WILEY

摘要:

AbstractPyramidal neurons in the rat hippocampal CA1 area contain mineralocorticoid (MRs) and glucocorticoid (GRs) receptors for corticosterone. Previous current clamp experiments showed that depolarizations evoked by carbachol(1–3 μM) depend on relative MR/GR occupation: carbachol responses are small with predominant MR‐activation and larger when both receptor types are occupied. Multiple K‐conductances underlie the carbachol‐induced depolarization. In the present study we used the single electrode voltage clamp technique to examine which K‐conductances modulated by carbachol are sensitive to corticosteroid treatment in vitro. We observed that 1 μM carbachol significantly reduced the IK, Leakwhile the IMwas hardly affected; carbachol effects on the IK, Leakwere significantly reduced under conditions of predominant MR activation compared to simultaneous activation of MRs and GRs. With a higher (10 μM) carbachol dose, steroid modulation of the IK, Leakshowed a similar tendency. The amplitude of the IMwas largely reduced by 10 μM carbachol but appeared to be not affected by steroid treatment. We conclude that the previously described suppression of the carbachol‐induced depolarization with predominant activation MRs is caused by an attenuation of the carbachol action on the IK, Leak. © 1995

ISSN:0887-4476    

DOI:10.1002/syn.890200403

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

年代:1995

数据来源: WILEY

摘要:

AbstractThis study examined interactions between the corticostriatal glutamatergic system and the nigrostriatal dopaminergic system via immunocytochemical examination of dopamine (DA) agonist induction of the striatal immediate early gene product Fos following cortical injury. After unilateral aspiration of the medial agranular cortex (AGm) region of prefrontal cortex, rats were tested for orientation to visual, tactile, and auditory stimuli. Fos immunoreactivity induced by d‐amphetamine (5 mg/kg) or apomorphine (5 mg/kg) was quantified in dorsolateral and ventrolateral regions of caudate‐putamen (CPu) in rats still demonstrating sensory neglect (5 days postsurgery) and in rats recovered from sensory neglect produced by AGm ablation (29+ days postsurgery). The pattern of immunoreactivity of rats still demonstrating neglect differed from that of unlesioned rats or recovered AGm‐ablated rats. In rats demonstrating sensory neglect, d‐amphetamine or apomorphine induction of Fos in the ipsilateral CPu was reduced by about 40% compared to the contralateral CPu or to comparable readings in unlesioned controls. These asymmetries were restricted to dorsolateral CPu, the region receiving the densest input from AGm. In contrast, recovered AGm‐ablated rats had DA agonist‐induced striatal Fos immunoreactivity that was symmetrical between the two hemispheres and comparable to control values. These findings indicate that adaptations involving the striatal medium spiny neuron, a site of convergence of cortical glutamatergic and nigral dopaminergic afferents, may contribute to recovery from behavioral deficits resulting from neocortical injury. © 1995 Wil

ISSN:0887-4476    

DOI:10.1002/syn.890200404

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

年代:1995

数据来源: WILEY

摘要:

AbstractAn iodinated cocaine derivative, N‐(3′‐iodopropen‐2′‐yl)‐2β‐carbomethoxy‐3β‐(4‐chlorophenyl)tropane (IPT), was evaluated as a probe for in vitro and in vivo labeling of dopamine (DA) and serotonin (5‐HT) transporters in Sprague‐Dawley rat brain. Saturation analysis of [125I]IPT in rat striatal homogenates, in two different buffer solutions, Tris‐HCl and phosphate, demonstrated a one‐site binding with affinities (Kd) of 0.25 ± 0.02 and 0.16 ± 0.02 nM and densities (Bmax) of 939 ± 161 and 1,982 ± 137 fmol/mg protein, respectively. Competition by known DA transporter ligands showed a rank order of RTI‐55>IPT>GBR12909>mazindol>(−)cocaine. Binding to 5‐HT transporter sites was evaluated in rat cortical homogenates. Saturation experiment results showed a single site with a Kdvalue of 1.2 ± 0.2 nM and a Bmaxvalue of 100 ± 20 fmol/mg protein. The rank order of potency of several monoamine uptake inhibitors (paroxetine>fluoxetine>mazindol>R‐nisoxetine>GBR12909) suggests that [l25I] IPT labels 5‐HT transporters in rat cortical homogenates. Both ex vivo and in vitro autoradiographic studies revealed high densities of [125I]IPT binding sites in the caudate nucleus, putamen, olfactory tubercle and nucleus accumbens, areas known to be rich in dopaminergic innervation. Moderate accumulation of activity was also observed in the substantia nigra. The dorsal raphe, a region with a high density of 5‐HT innervation, was labeled using in vitro autoradiography with [125I]IPT, but the labeling using ex vivo autoradiography was less prominent at 30 min postinjection and not noticeable at 60 min postinjection. Furthermore, systemic administration of IPT to rats increased the locomotor activity, a behavioral effect consistent with the in vitro and in vivo characteristics of compounds acting at dopaminergic sites. These results demonstrate that [125I]IPT is a useful ligand for in vitro labeling of DA and 5‐HT transporters and a ligand selective for labeling of DA transport sites in vivo. When labeled with I‐123,[123I]IPT holds promise as a SPECT imaging agent for studies of neuropsychiatric disorders

ISSN:0887-4476    

DOI:10.1002/syn.890200405

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe distribution of the D3and D2dopamine receptor subtypes in forebrain regions of the basal ganglia and mesocorticolimbic system was determined. This was assessed through combined fluorescent visualization of subtype selective anti‐peptide antibodies for these cloned receptors and detection of their ligand recognition sites using the D2subfamily antagonist,N‐(p‐aminophenethyl) spiperone (NAPS fluoroprobe). The double‐labeling technique enabled direct comparison of the cloned receptor proteins and NAPS fluoroprobe binding in vitro. The application of these two methods together produced results comparable to single‐labeling paradigms. Functional D3receptors, defined as the coincident fluorescence of the D3receptor antisera and fluoroprobe binding, were detected in the core region of the nucleus accumbens and exhibited a laminated expression pattern in the frontal cortex. D3receptor protein was expressed robustly in neurons of the dorsolateral striatum, but showed an intense neuropil reaction in the globus pallidus. Functional D2receptors, defined as the coincident fluorescence of the D2receptor antisera and fluoroprobe binding, were detected in the frontal cortex and the medial shell of the nucleus accumbens. Thus, heterogeneities occurred in the cellular expression of functional D3and D2receptors in forebrain dopaminoceptive areas. D3appears more related to basal ganglia and structures involved with motoric behavior, while D2was associated with regions associated with cognitive/affective functions. © 1995 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890200406

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

年代:1995

数据来源: WILEY

摘要:

AbstractExtracellular single‐unit recording techniques were used to examine the rat globus pallidus (GP). In both locally anesthetized, paralyzed rats and ketamine‐anesthetized rats, we observed two distinct biphasic extracellular waveforms, which we have labeled Type I (negative/positive waveform) and Type II (positive/negative waveform). No significant differences were observed in the firing pattern or number of cells per track between these cell types, although the Type II neurons had a faster mean firing rate in the locally anesthetized animals. A portion of both cell types could be antidromically activated from the subthalamic nucleus, although Type II neurons had significantly slower conduction velocities. The most striking pharmacological difference between the two cell types was that Type I GP neurons were inhibited by systemic administration of the dopamine agonist apomorphine; previous studies have repeatedly shown that Type II. GP cells are excited by this treatment. Pretreatment with a subthreshold dose of apomorphine reduced the responsiveness of Type I cells to a subsequent high dose of apomorphine, as has been shown for Type II cells. However, pretreatment with the NMDA antagonist dizocilpine (MK 801) produced a significant change in the pattern of response to apomorphine for Type II GP neurons only. Relative to observations in locally anesthetized, paralyzed rats, ketamine anesthesia reduced the firing rate of both cell types, but did not significantly alter their direction of response to apomorphine. Thus, this study has confirmed the existence of two GP cell types with distinct extracellular waveforms and different responses to dopamine receptor stimulation. These data may necessitate a reevaluation of general theoretical models of basal ganglia function in order to account for these opposite effects of dopamine receptor stimulation on pallidal output. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of A

ISSN:0887-4476    

DOI:10.1002/syn.890200407

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

年代:1995

数据来源: WILEY

摘要:

AbstractIn this study, we examined and characterized the action of the stereoisomers of 2‐amino‐4‐methyl‐Δ2‐5‐phenyl‐oxazoline (4‐methylaminorex, 4‐MAX) on spontaneously active dopamine (DA) neurons in the substantia nigra pars compacta (SNC or A9) and ventral tegmental area (VTA or A10) in anesthetized male rats. This was accomplished using the technique of extracellular single unit recording. The intravenous (i.v.) administration of the stereoisomers of 4‐MAX (0.1−6.4 mg/kg) produced a dosedependent suppression of the basal firing rate of A10 DA cells with the following rank order of potency: trans 4S,5S>cis 4R,5S ≈︁ cis 4S,5R ≫ trans 4S,5S 4‐MAX. The rank order of potency of the isomers of 4‐MAX to suppress the firing of A9 DA cells was trans 4S,5S = cis 4R,5S = cis 4S,5R ≫ trans 4R,5R. The trans 4S,5S isomer was 5‐fold more potent in suppressing DA cell firing in the A10 compared to the A9 area.The suppressant action of the isomers on A9 and A10 DA cells was reversed by the i.v. administration of haloperidol and the D2/D3receptor antagonists (−)‐sulpiride and (−)‐eticlopride but not by the D1receptor antagonists SCH 23390 and SCH 39166. In addition, the suppressant action of the trans 4S,5S isomer on A10 DA cells was not antagonized or reversed by the i.v. administration of the receptor antagonists granisetron (5‐HT3), ritanserin (5‐HT2A, C), idazoxan (α2), phentolamine (peripheral α1), (±)‐pindolol (5‐HT1A, Bβ) or prazosin (α1). The pretreatment of animals with either α‐methyl‐p‐tyrosine (AMPT) or reserpine, but not p‐chlorophenylalanine (PCPA), (±)‐fluoxetine or tomoxetine, significantly attenuated the suppression of A10 DA cell firing produced by trans 4S,5S 4‐MAX. Overall, our results suggest that the suppressant action of 4‐MAX on midbrain DA cell firing may be mediated by the release of DA,

ISSN:0887-4476    

DOI:10.1002/syn.890200408

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

年代:1995

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890200409

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

年代:1995

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890200401

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

年代:1995

数据来源: WILEY