摘要:

AbstractAlthough the molecular and cellular responses to injury in the central nervous system (CNS) have been widely investigated, few studies have examined the potential variations between direct and indirect neuronal injury. To differentiate between the response to axotomy and deafferentation, two central cholinergic populations were analyzed: the horizontal limb of the diagonal band of Broca (HLDB) and the interneurons in the corpus striatum (CS). At time points from one hour to eight weeks postinjury the levels of choline acetyltransferase (ChAT) mRNA and protein were assessed by in situ hybridization and immunohistochemistry. Also examined was the expression of the immediate early gene product, c‐fos. One week post axotomy, neurons in the HLDB exhibited an increase in the levels of ChAT mRNA without a concomitant increase in ChAT protein, followed by a steady decrease reaching a nadir in both parameters at eight weeks. In contrast, a transient increase occurred at one week postdeafferentation in the levels of both ChAT mRNA and protein in the interneurons of the CS. Axotomized neurons in the HLDB did not exhibit either c‐fos mRNA or protein expression, while robust fos induction occurred after one hour in deafferented neurons in the CS. These data demonstrate that the molecular and cellular responses differ following direct and indirect neufenal injury. Furthermore, they suggest that in these central cholinergic populations deafferentation may result in cellular hyperactivity and cell survival while axotomy, results in decreased cellular activity and subsequent cellular regression. © 1994 Wiley‐Lis

ISSN:0887-4476    

DOI:10.1002/syn.890160202

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe cocaine congener β‐CIT has been labeled with11C for positron emission tomographic (PET) studies of the dopamine transporter. In the present autoradiographic study on human' brain sections and PET study on monkey and human [11C]β‐CIT accumulated markedly in the striatum. [11C]β‐CIT binding in the striatum was selective to the dopamine transporter. The binding in the thalamus was on an intermediate level and was displaced by compounds having affinity for norepinephrine and serotonin transporters. The neocortical binding was on a low level and could be displaced only by citalopram, a serotonin uptake inhibitor. A high dose of cocaine intravenously (7 mg/kg) induced a 50% occupancy of specific [11C]β‐CIT binding to the dopamine transporter in the striatum. This dose is much higher than the doses of 0.25‐0.5 mg/kg i.v. for cocaine arousal in human subjects. The finding indicates that cocaine arousal may be induced at a low dopamine transporter occupancy of a few percent. [11C]β‐CIT should be a useful radioligand to explore cocaine actions in humans and to follow the pathophysiological process in vivo by PET in neurodegenerative diseases of the striatum. © 199

ISSN:0887-4476    

DOI:10.1002/syn.890160203

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe present experiments assessed the acute and delayed effects of D‐1 dopamine (DA) receptor blockade in the medial prefrontal cortex (mPFC) on pre‐ and postsynaptic indices of DA neurotransmission in the nucleus accumbens (N.Acc). Different groups of rats received intra‐mPFC injections of saline (control animals) or the D‐1 DA receptor antagonist SCH‐23390 (0.25 μg/side). Acutely, intra‐mPFC injections of this antagonist did not affect spontaneous locomotion but significantly increased the locomotion induced by intra‐N.Acc. amphetamine (1.5 μg /side), in agreement with our earlier findings [Vezina et al. (1991) Eur. J. Neurosci., 3:1001‐1007]. When tested two days post‐injection, however, mPFC‐SCH‐23390 preexposed animals showedlowerlevels of locomotor activity than Control animals in response to intra‐N.Acc. injections of amphetamine. This effect was not observed in other animals preexposed two days earlier to mPFC injections of amphetamine (2.5 tg/side) or the D‐2 DA receptor antagonist sulpiride (1.0 μg/side). Animals preexposed two days earlier to mPFC SCH‐23390 also showed higher levels of locomotor activity (+ 98%) when tested with intra‐N.Acc. injections of the D‐1 DA receptor agonist SKF‐38393 (1.0 μg/side) and a 36% increase in maximal DAsensitive adenylate cyclase activity in comparison to Control animals. These effects were no longer observed in animals tested seven days following the mPFC SCH‐23390 injections. These results demonstrate delayed actions resulting from cortical D‐1 DA receptor blockade. They suggest, in a way consistent with previous findings [Herve et al. (1989) J. Neurosci., 9:3699‐3708] that mPFC D‐1 DA receptors are involved in the presynaptic regulation of DA neuron reactivity as well as the postsynaptic regulation of D‐1 DA receptors in subcortical DA terminal and receptor f

ISSN:0887-4476    

DOI:10.1002/syn.890160204

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

年代:1994

数据来源: WILEY

摘要:

AbstractDehydroepiandrosterone sulfate (DHEAS) blocked the GABAAreceptor noncompetitively in neurons grown in primary culture from the ventral midbrains of fetal rats. The apparent dissociation constant for this blockade was 4.5 μ, and one molecule of DHEAS was sufficient to block the receptor. The affinity of the blocked receptor for GABA was diminished by about one half. The findings that the DHEAS caused no rectification of chloride currents and that it did not shorten the durations of open ion channels indicated that DHEAS did not act by occluding open ion channels. Neither did it diminish their conductance. DHEAS accelerated desensitization in at least one population of receptors, diminished the amplitudes of inhibitory postsynaptic currents, and shortened their decay time constants in a concentration dependent manner. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of Amer

ISSN:0887-4476    

DOI:10.1002/syn.890160205

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

年代:1994

数据来源: WILEY

摘要:

AbstractMuscarinic‐type acetylcholine (ACh) receptors are involved in a variety of cortical functions. ACh “activates” neocortex; simultaneously modifying spontaneous subthreshold activity, intrinsic neuronal oscillations and spike discharge modes, and responsiveness to fast (putative glutamatergic) synaptic inputs. However, beyond the general involvement of muscarinic receptors, a mechanistic understanding of integrated cholinergic actions, and interactions with non‐cholinergic transmission, is lacking. We have addressed this problem using intracellular recordings from the in vitro auditory neocortex. First, we investigated cholinergic modification of responses to the excitatory amino acid glutamate. ACh, or the muscarinic agonist methacholine, produced a lasting enhancement of glutamate‐mediated membrane depolarizations. Muscarinic receptors of the M1and/or M3subtype, rather than M2or nicotinic receptors, mediated this enhancement. Subsequently, we investigated whether second messenger systems contribute to observed muscarinic actions. Activation of protein kinase C with phorbol 12,13‐dibutyrate (4 β‐PDBu), enhanced neuronal responses to glutamate. The effect of 4 β‐PDBu was attenuated by the kinase antagonist H7. Finally, we attempted to identify postsynaptic actions ofendogenousACh. Tetanic stimulation of cholinergic afferents elicited voltage‐dependent effects, including reduced spike frequency adaptation and reduced slow afterhyperpolarization (sAHP) elicited by transmembrane depolarizing stimuli. These effects were mimicked by methacholine, enhanced by eserine, and antagonized by muscarinic receptor antagonists. These data suggest that cholinergic modulation in neocortex likely involves the integrated actions of diverse mechanisms, primarily gated by muscarinic receptors, and at least partly involving second messenger systems. ©

ISSN:0887-4476    

DOI:10.1002/syn.890160206

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

年代:1994

数据来源: WILEY

摘要:

AbstractAcute administration of morphine (10 mg/kg) to rats elicited an increase in locomotion that became sensitized upon repeated treatment over 14 days. Administration of the noncompetitive N‐methyl‐D‐aspartate receptor (NMDA) antagonist MK‐801 (0.1 or 0.25 mg/kg) prior to each morphine injection prevented the development of behavioral sensitization to morphine, an effect that persisted even after a 7‐day withdrawal from repeated treatment. Sensitization was also prevented by coadministration of the competitive NMDA receptor antagonist CGS 19755 (10 mg/kg). In contrast, acute pretreatment with MK‐801 did not alter the response of sensitized rats to morphine challenge, indicating that MK‐801 does not prevent the expression of sensitization. When administered alone, MK‐801 produced stereotyped movements at moderate doses (0.25 rng/kg) and horizontal locomotion at higher‐ doses, (0.5 mg/kg). Repeated administration of 0.25 mg/kg MK‐801 elicited sensitization to its own locomotor stimulatory effects, such that this dose became capable of eliciting horizontal locomotion. Sensitization was not seen during repeated administration of 0.1 mg/kg MK‐801 or 10 mg/kg CGS 19755, although both of these pretreatments did produce a sensitized response to subsequent challenge with 0.25 mg/kg MK‐801. This effect was enhanced by coadministration of morphine, even though repeated administration of morphine alone failed to sensitize rats to MK‐801 challenge. These results suggest a complex interplay between NMDA and opioid receptors, such that NMDA antagonists prevent morphine sensitization while morphine enhances the ability of NMDA antagonists to elicit sensitization to their own locomotor stimulatory effect

ISSN:0887-4476    

DOI:10.1002/syn.890160207

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

年代:1994

数据来源: WILEY

摘要:

AbstractBy connecting the fascia dentata with the hippocampus proper, the axons of the granule cells, the mossy fibers, represent an important element of the main excitatory, trisynaptic pathway of the hippocampal formation. In this review the various synaptic connections of the mossy fibers are discussed. It turns out that the mossy fibers do not only establish synapses with the pyramidal neurons of regio inferior as traditionally assumed, but a variety of local circuit neurons as well as projection cells are also contacted by the mossy fibers. Thus there is an underestimated divergence of the impulse flow within the “trisynaptic” pathway at the level of the mossy fibers. Similarly, the pattern of afferent input to the granule cells, especially that of GABAergic neurons, is more complex than previously assumed. In this respect the concept of a unidirectional “trisynaptic” pathway certainly is an oversimplification. In particular, the hilus of the fascia dentata, that the 'mossy fibers traverse on their way to regio inferior, is often neglected in this concept. The hilar region comprises a large variety of morphologically and functionally distinct neuronal types that, to a large extent, are targets of hilar mossy fiber collaterals. By focusing on the mossy fiber system, an attempt is made in this review to summarize new data on hippocampal circuitries that have been accumulated since the original description of the trisynaptic pathway. This concept, which originally comprised the synapses of the perferant path fibers on dentate granule cells, the mossy fiber synapses on CA3 pyramidal neurons, and the synapses of the Schaffer collaterals on CA1 pyramidal cells, has been of great heuristic value but needs to be modified in view of recent morphological and physiological data. © 1994 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890160208

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.890160201

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

年代:1994

数据来源: WILEY