摘要:

AbstractWe have used autoradiographic techniques to examine the characteristics and distribution of the binding of reported selective M2muscarinic ligands and compared them with the distribution of cells expressing mRNAs for the different subtypes of muscarinic receptors. Our results suggest that the M2ligands used in the present study ([3H]OXO‐M, [3H]AF‐DX 384, AF‐DX 116, methoctramine) also recognize M4receptors present in regions such as the striatum and olfactory tubercle. This is supported by (1) relative abundances of the different transcripts, with m2 mRNA being very scarce and m4 mRNA very abundant in these regions; (2) comparison of the pharmacological characteristics of M2‐ligand binding sites in brain areas selected by their exclusive expression of M2receptors versus areas enriched in M4receptors. An important conclusion of these studies is that none of the muscarinic radioligands available at the present time appears to label specifically a single muscarinic receptor subtype population. Areas are suggested where autoradiographic techniques can be helpful in elucidating the subtype selectivity of existing and new ligands. © Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890110302

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

年代:1992

数据来源: WILEY

摘要:

AbstractNeurological complications from cocaine use are well recognized. We propose that chronic cocaine use can also cause clinically silent brain dysfunction.We investigated brain glucose metabolism with positron emission tomography (PET) and 2‐deoxy‐2[18F] fluoro‐D‐glucose (FDG) in 21 neurologically intact chronic cocaine abusers (C) and 18 normal controls (N). The cocaine abusers were tested 1–6 weeks after the last use of cocaine and seven were retested after a 3 month drug‐free period.Global cerebral glucose metabolism was not significantly different between controls and cocaine abusers (N = 38.4±3, C = 36.5±5 μmol/100 g of tissue, min). However, cocaine abusers had significantly (P<0.05) lower metabolic activity in 16 of the 21 left frontal regions and 8 of the 21 right frontal regions. These decreases persisted after 3–4 months of detoxification and were correlated with the dose (P≤ 0.01) and the years of cocaine use (P≤ 0.05).This study shows reduced rates of frontal metabolism in neurologically intact cocaine abusers that persist even after 3–4 months of detoxificat

ISSN:0887-4476    

DOI:10.1002/syn.890110303

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

年代:1992

数据来源: WILEY

摘要:

AbstractAdenosine‐induced inhibition of evoked postsynaptic potentials (PSPs) and epileptiform burst firing in the CA1 subfield of rat hippocampal slices was studied with intracellular recordings in vitro. Adenosine (50 μM) caused a membrane hyperpolarization which was abolished during superfusion with 2 mM Ba2+. The adenosine‐induced inhibition of the PSPs was still evident, although the magnitude of the effect was significanty reduced. Adenosine also reduced Ba2+‐induced burst firing, but less effectively than it did bursts evoked by TEA (5 mM). The results suggest that adenosine inhibits synaptic transmission and epileptiform activity by at least 2 mechanisms: a postsynaptic barium‐sensitive increase in gKand a presynaptic effect independent of this adenosine‐evoked outward potassium conductance. © Wile

ISSN:0887-4476    

DOI:10.1002/syn.890110304

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

年代:1992

数据来源: WILEY

摘要:

AbstractImmunocytochemical and electrophysiological evidence supporting the presence of GABAergic interneurons in the turtle red nucleus is presented. Injections of HRP into the spinal cord produced labeling of large neurons in the contralateral red nucleus. The peroxidase‐antiperoxidase (PAP) method revealed smaller cells immunoreactive to an antibody against glutamate decarboxylase (GAD), the synthetic enzyme for the inhibitory neurotransmitter GABA, that were interspersed among larger immunonegative neurons. Similar small neurons were densely immunostained by antibodies to GABA‐glutaraldehyde conjugates obtained from different sources and applied according to pre‐embedding and postembedding protocols. Rubrospinal neurons retrogradely labeled with HRP measured 16 and 27 μm in mean minor and major cell body diameters, while GABA‐like immunopositive neurons situated within the red nucleus measured 7 and 13 μm. There was very little overlap in soma size between the two cell populations. Therefore, we suggest that the GAD‐ and GABA‐positive neurons may be local inhibitory interneurons. This nition is further supported by observations of pre‐embedding immunostaining for GAD and postembedding immunostaining for GABA showing that the turtle red nucleus is amply innervated by immunoreactive axon terminals. These puncta are closely apposed to cell bodies and dendrites of both immunonegative large neurons and immunopositive small neurons. Moreover, immunogold staining at the electron microscopic level demonstrated that GABA‐like immunoreactive axon terminals with pleomorphic synaptic vesicles formed symmetric synapses with cell bodies and dendrites of the two types of red nucleus cells. These ultrastructural features are commonly assumed to indicate inhibitory synapses. A moderately labeled bouton with round vesicles and asymmetric synapses was also observed. In addition, the two types of red nucleus neurons received asymmetric axosomatic and axodendritic synapses with GABA‐negative boutons provided with round vesicles, features usually associated with excitatory functions. To obtain electrophysiological evidence for inhibition, intracellular recordings from red nucleus neurons were conducted using an in vitro brainstem‐cerebellum preparation from the turtle. Small, spontaneous IPSPs were recorded from 7 out of 14 red nucleus cells studied.These morphological and physiological results provide strong support for concluding that the turtle red nucleus, like its mammalian counterpart, contains GABAergic inhibitory interneurons. While we have not indentified the main source of input to these interneurons, in view of the scarce development of the reptilian cerebral cortex, this input is unlikely to come from the motor cortex as it does in mammals. Current concepts of the role of these interneurons in motor control must take into account the presence of this interneuronal system that phylogenetically precedes the emergence of the sensorimotor cort

ISSN:0887-4476    

DOI:10.1002/syn.890110305

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

年代:1992

数据来源: WILEY

摘要:

AbstractNociceptive dorsal horn neurones, which are involved in the processing of pain‐related information, are inhibited by input from vibration‐sensitive, large diameter primary sensory fibres (Wall and Cronly‐Dillon, 1960; Salter and Henry, 1990a, b). We have reported previously that the inhibition of spinal nociceptive neurones by vibration is mediated by adenosine acting through P1‐purinergic receptors (Salter and Henry, 1987). In a number of different types of cell, adenosine is known to activate K+currents (Gerber et al., 1989; Greene and Haas, 1985; Proctor and Dunwiddie, 1987; Segal, 1982; Trussell and Jackson, 1987) and we have recently found that the adenosine‐mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP), which is, indeed, caused by a K+conductance (De Koninck and Henry, 1988, 1992). It has been reported that adenosine‐activated K+channels in cardiac muscle cells are the ATP‐sensitive K+channels (Kirsch et al., 1990). Therefore, we questioned whether these channels might mediate the purinergic IPSP we have observed in nociceptive dorsal horn neurones. We report here that glibenclamide, a blocker of ATP‐sensitive K+channels (Ashcroft, 1988; Schmid Antomarchi et al., 1987a, b), blocks the inhibition of nociceptive neurones by vibratory stimulation when this compound is administered locally by iontophoresis or systemically by intravenous injection. In addition, direct intracellular injection of ATP was found to block the IPSP evoked by vibratory stimulation. These data indicate that the purinergic IPSP in nociceptive spinal neurones is mediated via ATP‐sensitive K+channels. As inhibition of nociceptive dorsal horn neurones may be the physiological basis for the analgesia produced by vibratory stimulation in humans (Bini et al., 1984; Lundeberg, 1984; Lundeberg et al., 1984; Ottoson et al., 1981), we propose that activation of ATP‐sensitive K+channels in these neurones may mediate the analgesia produced by vibration

ISSN:0887-4476    

DOI:10.1002/syn.890110306

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe effects of the novel competitiveN‐methyl‐D‐aspartate (NMDA) receptor antagonist, CGP 39551 [the carboxyethylester of CGP 37849;DL‐(E)‐2‐amino‐4‐methy‐5‐phosphono‐3‐pentenoic acid], on extracellular field potentials and long‐term potentiation (LTP) induced in the dentate gyrus by stimulation of the perforant path were studied in anesthetized rats. CGP 39551 attenuated the population spike (PS) and excitatory postsynaptic potential (EPSP) amplitude of dentate field potentials, reduced the NMDA receptor‐mediated component of train‐evoked burst potentials, and prevented the induction of LTP. The decrease in PS and EPSP amplitude produced by CGP 39551 was observed mainly in non‐potentiated synaptic populations; potentiated field potentials were only minimally affected by drug treatment. These results are consistent with the in vivo blockade of NMDA receptors by CGP 39551. They also indicate that NMDA receptors may contribute in a tonic manner to the state of dentate granule cell excitability. Finally, the differential modulation of potentiated and non‐potentiated synapses by CGP 39551 suggests that a change in some properties of postsynaptic AMPA receptors is involved in the exp

ISSN:0887-4476    

DOI:10.1002/syn.890110307

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe rates and patterns of discharge activity exhibited by 16 spontaneously active substantia nigra pars compacta dopamine neurons were studied in halothane‐anesthetized rats using three types of quantitative measures: (1) mean discharge rates, (2) population characteristics of interspike interval samples, and (3) interspike interval time‐series measures which were used to examine patterns in the ordering of interspike intervals. The mean discharge rate of these 16 cells was 2.9 ± 0.3 spikes/sec, and each cell was classified as bursting (25% of the cells) or non‐bursting (75%). The distribution of interspike intervals of bursting cells was typically positively skewed and sometimes bimodal, while the interspike intervals of non‐bursting neurons were more normally distributed. Time‐series analyses (raw time‐series plots, return maps, and phase portraits) revealed a substantial oscillatory tendency in the magnitudes of consecutive interspike intervals in these neurons under baseline conditions: Successive interspike intervals tended to alternate between short and long durations, although short bursts often occurred. Under baseline conditions, these cells exhibited both multispike bursts and consecutive long intervals less frequently than would have been predicted by chance ordering of the interspike intervals. These results imply that there are mechanisms acting to reduce the probability of these types of events.Locally infused nicotine enhanced discharge rates in these neurons. Burst firing increased in four neurons, while five neurons did not show any change in burst firing. LY 163502 induced significant decreases in both discharge rate and bursting activity in all cells tested. The variation coefficient, skew, and kurtosis of the interspike interval distributions were not consistently altered by either drug. The local infusion of either nicotine or LY 163502 decreased the oscillatory phenomenon seen in the baseline condition. Neither the nicotine or LY 163502 time‐series data exhibited a larger proportion of long‐short and short‐long pairs (relative to the median interval) than would be expected by chance.It is hypothesized that these neurons have intrinsic mechanisms, made manifest under anesthesia, which induce oscillations in interspike interval length. The oscillatory effect of these mechanisms can be overridden by tonic increases in either excitatory or inhibitory tone.

ISSN:0887-4476    

DOI:10.1002/syn.890110308

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

年代:1992

数据来源: WILEY

摘要:

AbstractFollowing micropressure application of glutamate (500 μM) instratum lacunosum‐moleculare(L‐M), inhibitory postsynaptic potentials (glut‐IPSPs) were recorded in CA1 pyramidal cells. These glut‐IPSPs were blocked by tetrodotoxin (1 μM) and, thus, were probably generated by the activation of local interneurons. The effects of pharmacological antagonists on glut‐IPSPs and on electrically‐evoked early and late IPSPs were assessed in the same cells during the same application of the antagonist. Local application of the GABABantagonist 2‐OH saclofen (1–4 mM) reduced both glut‐IPSPs and late IPSPs but not early IPSPs. In contrast, the GABABantagonist phaclofen (20 mM) reduced late IPSPs but not early IPSPs or glut‐IPSPs. Early IPSPs were blocked by the GABAAantagonists bicuculline and picrotoxin but late IPSPs and glut‐IPSPs were not. Repetitive electrical stimulation depressed early and late IPSPs as well as glut‐IPSPs, suggesting that interneurons activated with glutamate were also stimulated electrically. Thus, interneurons instr. lacunosum‐moleculareappear to inhibit pyramidal cells via a GABABreceptor‐mediated IPSP. The discrepancy in the pharmacological profile of the GABABglut‐IPSPs and of the GABABlate IPSPs may suggest the presence of two GABABmechanisms in CA1 pyramida

ISSN:0887-4476    

DOI:10.1002/syn.890110309

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

年代:1992

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890110310

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

年代:1992

数据来源: WILEY

摘要:

AbstractRats were exposed to restraint coupled with 60, 1‐sec, 1‐mA, 60‐Hz tail shocks. One hippocampus was immediately dissected for in vitro measurement of pairedpulse facilitation and LTP of the excitatory postsynaptic potential (EPSP) recording from the stratum radiatum of field CA1. There was no change in paired‐pulse facilitation, suggesting that acute exposure to the stressor does not result in a decrease in presynaptic neurotransmitter release. There was, however, a significant decrease in the percent LTP produced by theta burst stimulation relative to naïve controls. These results are consistent with the hypothesis that the stress‐induced impairment of LTP is a result of changes in the postsynaptic glutamate receptors, specifically the AMPA type. © Wile

ISSN:0887-4476    

DOI:10.1002/syn.890110311

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

年代:1992

数据来源: WILEY