摘要:

AbstractThe functional consequences of chronic treatment with haloperidol (0.5 mg/kg s. c. for 21–23 days) on striatal extracellular levels of dopamine and excitatory amino acids, aspartate and glutamate, were examined using microdialysis techniques. Our studies indicate that, in both awake and anesthetized animals, chronic haloperidol treatment does not appear to change basal outflow of dopamine and its response to an exogenous antagonist (i. e., a challenge dose of haloperidol). Furthermore, in chronic haloperidol and vehicle‐treated animals, extracellular dopamine levels were decreased below our limit of detection following perfusion of tetrodotoxin through the probe, or into the medial forebrain bundle, suggesting that in both groups of animals extracellular dopamine levels are neuronally derived and seemed to depend equally on impulse flow. However, some differences were observed between the vehicle and haloperidol‐treated animals: the excitatory action of 30 mM K+on extracellular dopamine levels was decreased, and extracellular levels of glutamate were significantly increased, in animals treated chronically with haloperidol. The alterations in extracellular glutamate levels suggests that events at the terminal may be involved in maintaining the “normal” extracellular dopamine levels. Furthermore, the decrease in response to stimulation by K+suggests that chronic haloperidol treatment may decrease the responsivity of the striatal dopamine system to stimuli. © 1993 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890140302

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

年代:1993

数据来源: WILEY

摘要:

AbstractAlthough tissue culture studies have shown a variety of neurotransmitter receptors on astroglial cells, verifying these observations in adult animals has been difficult and rarely accomplished. In the current study we have used double immunocytochemistry to localize 5‐HT1Areceptors to astroglial cells in fixed sections of adult rat brain. The astroglial cells were identified using an antibody raised against the astroglialspecific protein glial fibrillary acidic protein (GFAP). To label the 5‐HT1areceptor, we used an antibody we recently raised against a unique peptide sequence occurring in the second extracellular loop of the receptor.Our results show that the 5‐HT1areceptor occurs in relatively high abundance on astroglial cells. There is regional specificity, the receptor being much more commonly found is septum and hippocampus than striatum. There are also intraregional differences in that even within a single brain region one astrocyte may have very high levels of the receptor while an adjacent cell has none.We propose that the cellular localization of this receptor could have significance in understanding the mechanism of action of 5‐HT1areceptor active drugs in alleviating anxiety and depression. The mechanism may be through the release of a neurotrophic agent, S‐100β, from astrocytes. This factor may then cause regeneration or sprouting of neuronal terminals which have been lost due to a disease process. © 1993 Wile

ISSN:0887-4476    

DOI:10.1002/syn.890140303

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

年代:1993

数据来源: WILEY

摘要:

AbstractAs a model for an integrated neuronal network based on the concept of modular units, we have investigated the occurrence of spontaneous activity and the formation of synaptic circuits in primary cultures of dissociated hippocampal neurons from the embryonic rat. Sodium‐dependent action potentials (APs) could be elicited after 1 day in vitro (DIV), whereas spontaneous postsynaptic potentials (PSPs), “miniature” PSPs and APs appeared after 3‐6 DIV. The number of cells with spontaneous APs and the rate of APs increased during development of the neuritic network. In addition to a stochastic spike interval distribution, pyramid‐shaped neurons could be identified after 10‐12 DIV, which fired preferentially at interspike intervals between 20‐120 ms and 190‐400 ms. This distinctive bimodal interspike interval pattern was sensitive to GABA‐A antagonists. Simultaneous recordings of pairs of neurons demonstrated recurrent inhibitory, GABA‐ergic synaptic circuits. In addition, a subpopulation of GABAergic neurons could be visualized by immunocytochemistry. These results are discussed in relation to the hypothesis that spontaneous firing of connected neurons is networkdriven, based on synaptic “noise” and patterned by recurrent inhibition.

ISSN:0887-4476    

DOI:10.1002/syn.890140304

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn primary cultures of hippocampal neurons from the embryonic rat, spontaneous depolarizations lasting up to 6 sec adn resembling paroxysmal depolarization shifts (PDAs) appeared after 11 day7s in vitro. These depolarizations are presumably generated by sy6naptic events, because: (1) both their appearance and duration are independent of membrane potential, (2) the amplitudes of the underlying currents depend monotonically on membrane potential, and (1) they are reversed at the reversal potential of the excitatory postsynaptic potentials (EPSPs). In addition, PDAs disappeared reversiblyy when sodium‐dependent action potentials were blocked by tetrodotoxin (10μM) and when synaptic transmission was reduced by elevated Mg2+(5mM). Further, the fact that these depolarizations can apppear simultaneously in two neurons in paired recordings also points to a synaptic origin. Inhibition of glutaminergic synaptic transmission by kynurenic acid (50μM) and the NMDA‐antagonist D‐2‐amino‐5‐phosphonovaleric acid (APV; 50μM) led to a marked shortening of the depolarizations. This blocking effect of kynurenic acid and APV and comparison with the currents elicited by locally applied glutamate or NMDA provide evidence for an activation of both types of glutamate receptors to induce PDSs. The role of alteration of glutaminergic synaptic transmission in the induction and maintenance of these depolarizations is discussed in the context of results from the literature on the appearrance of PDSs in cultures grown under chronic blockade of glutamate receptors. © 1993

ISSN:0887-4476    

DOI:10.1002/syn.890140305

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe influence of γ‐aminobutyric acidB(GABAB) receptor stimulation on the excitatory and inhibitory synaptic potentials and membrane properties of identified striatal spiny neurons was examined in a corticostriatal slice preparation. Stimulation of the subcortical white matter evoked a monosynaptic, excitatory postsynaptic potential (EPSP) and a polysynaptic, inhibitory postsynaptic potential (IPSP) in spiny neurons. The EPSP had two components: a large amplitude response which could be blocked by the kainate/quisqualate receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 10μM), and a small amplitue, long‐duration depolarization which could be blocked by the N‐methyl‐D‐aspartate receptor antagonist, d‐(‐)‐2‐amino‐5‐phosphonovaleric acid (APV, 100 μM). The IPSP was observed as a membrane depolarization when recorded from neurons at resting membrane potential. However, when neurons were injected with the Na+‐channel blocker, QX‐314, allowing cells to be depolarized above their spike thresholds, a prominent hyperpolarizing IPSP was readily observed which could be blocked by the GABAAantagonist, bicuculline (10‐50 μM). This bicuculline‐sensitive IPSP was responsible for the inhibition of EPSP amplitude and probability of spike discharge revealed using paired stimulation of the subcortical white matter. The amplitude of both the EPSP and the IPSP were depressed by the GABABreceptor agonist,p‐chlorophenyl‐GABA (baclofen, 0.5‐100 μM) in a concentration‐dependent manner. Baclofen also blocked paired stimulus inhibition of spike discharge. These effects of baclofen persisted in slices in which the cortex was removed and were reversed by the GABABreceptor antagonist, 3‐amino‐3‐hydroxy‐2‐(4‐chlorophenyl)‐propanesulphonic acid (saclofen, 100‐500 μM). In contrast to its profound influence on synaptic input, baclofen did not alter resting membrane potential, input resistance, membrane current‐voltage relationship, or spike threshold of the cells recorded, and therefore did not appear to exert direct postsynaptic effects on the striatal spiny neurons.Taken together, these data indicate that the depressant effects of baclofen on EPSPs are mediated through GABABreceptors located on the terminals of glutamatergic afferents within the striatum. Moreover, the results suggest that the actions of baclofen on IPSPs and paired stimulus inhibition are produced by activation of GABABreceptors within the striatum at a site presynaptic to spiny neurons, either on the terminals of GABAergic afferents or on an interposed non‐spiny GABAergic cell. Thus, GABABhetero‐ and auto‐receptors have the capacity to provide a negative feedback mechanism through which the major excitatory and inhi

ISSN:0887-4476    

DOI:10.1002/syn.890140306

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

年代:1993

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890140307

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

年代:1993

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890140301

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

年代:1993

数据来源: WILEY