The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform
Loris A. Chahl - One of the best experts on this subject based on the ideXlab platform.
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localization of fos like immunoreactivity induced by the nk3 tachykinin receptor agonist senktide in the guinea pig brain
British Journal of Pharmacology, 1997Co-Authors: Jane Yip, Loris A. ChahlAbstract:1. The effects of intracerebroventricular (i.c.v.) administration of the NK3 tachykinin receptor agonist, senktide (10 nmol each side), in guinea-pigs pretreated with the selective NK3 tachykinin receptor antagonist, SR142801 (3 mg kg(-1) subcutaneous, s.c., 30 min before senktide), or its less active enantiomer, SR142806 (3 mg kg(-1) s.c. 30 min before senktide), on behaviour and on the distribution of Fos-like immunoreactivity (Fos-LI) in Central Neurones were investigated. Guinea-pigs were chosen for the study since they possess NK3 tachykinin receptors with pharmacological characteristics similar to those in man. 2. Wet-dog shakes, but not locomotor activity, elicited by senktide i.c.v. were significantly reduced by SR142801 but not by SR142806, confirming the involvement of NK3 tachykinin receptors in wet-dog shake behaviour. 3. Senktide induced increased numbers of Fos-LI Neurones in the following brain areas: frontal, parietal and piriform cortex, the lateral septum, the CA1, CA2, subiculum and dentate gyrus of the hippocampus, most areas in the amygdala, thalamus and hypothalamus, medial geniculate nucleus and the ventral cochlear nucleus. Pretreatment with SR142801, but not with SR142806, before administration of senktide inhibited Fos-LI expression in the cingulate cortex, dentate gyrus of the hippocampus, some regions of the thalamus, hypothalamus and amygdala and the ventral cochlear nucleus. 4. The present results are the first demonstration that senktide induces Fos-LI in widespread areas of the guinea-pig brain. It is proposed that NK3 tachykinin receptors may play a more extensive role in the control of diverse brain functions, including cortical processing, learning and memory, neuroendocrine and behavioural regulation, than is currently recognized.
Po Wu Gean - One of the best experts on this subject based on the ideXlab platform.
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inhibition of synaptic transmission and epileptiform activity in Central Neurones by fluspirilene
British Journal of Pharmacology, 1997Co-Authors: Sujane Wang, Kwok Tung Lu, Po Wu GeanAbstract:Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a long-acting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity. In the present study, we have investigated the effect of fluspirilene on synaptic transmission and epileptiform activity induced in slices of hippocampus and amygdala. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f-e.p.s.p) in a concentration-dependent manner in the area CAl of the hippocampus without affecting the size and shape of fibre volley. Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala Neurones without affecting the resting membrane potential or neuronal input resistance. Fluspirilene increased the ratio of paired-pulse facilitation suggesting a presynaptic mode of action. Epileptiform activity induced in the disinhibited slices was suppessed by fluspirilene in a concentration-dependent manner. This antiepileptic effect was occluded in slices pretreated with the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA). It is concluded that fluspirilene-induced synaptic inhibition is probably due to a reduction in presynaptic Ca2+ currents. In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity. British Journal of Pharmacology (1997) 120, 1114–1118; doi:10.1038/sj.bjp.0701008
Enrico Cherubini - One of the best experts on this subject based on the ideXlab platform.
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bk potassium channels control transmitter release at ca3 ca3 synapses in the rat hippocampus
The Journal of Physiology, 2004Co-Authors: Giacomo Raffaelli, Chiara Saviane, Majid H Mohajerani, Paola Pedarzani, Enrico CherubiniAbstract:Large conductance calcium- and voltage-activated potassium channels (BK channels) activate in response to calcium influx during action potentials and contribute to the spike repolarization and fast afterhyperpolarization. BK channels targeted to active zones in presynaptic nerve terminals have been shown to limit calcium entry and transmitter release by reducing the duration of the presynaptic spike at neurosecretory nerve terminals and at the frog neuromuscular junction. However, their functional role in Central synapses is still uncertain. In the hippocampus, BK channels have been proposed to act as an ‘emergency brake’ that would control transmitter release only under conditions of excessive depolarization and accumulation of intracellular calcium. Here we demonstrate that in the CA3 region of hippocampal slice cultures, under basal experimental conditions, the selective BK channel blockers paxilline (10 μm) and iberiotoxin (100 nm) increase the frequency, but not the amplitude, of spontaneously occurring action potential-dependent EPSCs. These drugs did not affect miniature currents recorded in the presence of tetrodotoxin, suggesting that their action was dependent on action potential firing. Moreover, in double patch-clamp recordings from monosynaptically interconnected CA3 pyramidal Neurones, blockade of BK channels enhanced the probability of transmitter release, as revealed by the increase in success rate, EPSC amplitude and the concomitant decrease in paired-pulse ratio in response to pairs of presynaptic action potentials delivered at a frequency of 0.05 Hz. BK channel blockers also enhanced the appearance of delayed responses, particularly following the second action potential in the paired-pulse protocol. These results are consistent with the hypothesis that BK channels are powerful modulators of transmitter release and synaptic efficacy in Central Neurones.
Steven W Johnson - One of the best experts on this subject based on the ideXlab platform.
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rebound bursts following inhibition how dopamine modifies firing pattern in subthalamic neurons
The Journal of Physiology, 2008Co-Authors: Steven W JohnsonAbstract:The subthalamic nucleus (STN) is a member of the basal ganglia that has long been implicated in the expression of a variety of movement disorders. However, the importance of the STN in movement disorders has been reinforced by the recent acceptance of STN deep brain stimulation for the treatment of advanced Parkinson's disease. For many years it was hypothesized that increased neuronal activity in the STN contributed to the rigidity and bradykinesia seen in Parkinson's disease, whereas reduced STN output contributed to chorea and other hyperkinetic movements (DeLong, 1990). However, there has been a more recent appreciation that expression of symptoms of Parkinson's disease correlate better with excessive burst firing of action potentials in STN Neurones, rather than an overall increase in firing rate (Bergman et al. 1994). In fact, excessive burst firing in basal ganglia such as the STN has become accepted as a physiological hallmark of parkinsonism (Bergman et al. 1998). Thus, much attention is now focused on firing pattern of STN Neurones rather than absolute firing rate regarding the influence of basal ganglia output on manifestations of movement disorders. Because the classical symptoms of Parkinson's disease are caused by a loss of dopamine innervation, there has been much interest in characterizing the actions of dopamine in the STN. The prevailing hypothesis is that dopamine receptor stimulation attenuates Parkinson's disease symptoms because it acts to diminish burst firing in STN Neurones. But how this might be accomplished is unclear. Stimulation of postsynaptic dopamine D2-like receptors has been shown to depolarize STN Neurones, which takes membrane potential beyond the range at which burst firing can be sustained (Beurrier et al. 1999; Zhu et al. 2002). However, in this issue of The Journal of Physiology, Baufreton & Bevan (2008) highlight another mechanism by which dopamine may impair burst firing. Using perforated patch and whole-cell recording techniques in slices of rat brain, these authors show that dopamine, by stimulation of D2-like receptors, causes presynaptic inhibition of GABA-mediated inhibitory postsynaptic currents (IPSCs). Although this confirms previous studies (Shen & Johnson, 2000), the present work extends these studies by showing the consequence of IPSC inhibition on rebound firing patterns. Using the dynamic clamp technique to mimic GABA-mediated synaptic currents, Baufreton and Bevan show that an inhibitory synaptic current is followed by a rebound burst of action potentials. Previous studies have shown that the rebound burst is caused by de-inactivation of voltage-dependent calcium channels, of which STN Neurones express in abundance (Song et al. 2000). By reducing the conductance associated with GABA-mediated synaptic currents, this disrupts rebound burst firing as well as the ability of the synaptic current to reset the spontaneous firing of action potentials (Fig. 1). Thus, the data presented by Baufreton and Bevan show that the dopamine-mediated suppression of synaptic inhibition may produce a paradoxical result that impairs rebound excitation. In this way, dopamine may act to suppress synaptically triggered burst firing. Figure 1 Schematic representation of spontaneous action potentials in an STN neuron in the presence and absence of dopamine Arrow signifies onset of GABA-mediated inhibitory postsynaptic potential. Note the reduction in rebound burst in the presence of dopamine. ... Regulation of neuronal activity often is mediated by what may seem to be complex and indirect mechanisms. For example, neuronal disinhibition is a common mechanism for increasing neuronal output, in which inhibition of an inhibitory input results in neuronal excitation (Chevalier & Deniau, 1990). The paper by Baufreton and Bevan illustrates another paradoxical mechanism, in which a burst firing pattern may be suppressed by reducing the conductance associated with an inhibitory synaptic current. Thus, one must be careful not to assume that the only function of inhibitory input is to suppress excitability. In the case of the STN, suppression of GABA release by dopamine appears to exert a paradoxical action to reduce the burst firing that may be associated with symptoms of Parkinson's disease. As shown by Baufreton and Bevan, this illustrates the need to examine neurotransmitter actions in a dynamic context in order to fully understand the functional impact of neurotransmitter receptor activation in Central Neurones.
Alireza Asgari - One of the best experts on this subject based on the ideXlab platform.
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the functional consequences of paraoxon exposure in Central Neurones of land snail caucasotachea atrolabiata are partly mediated through modulation of ca2 and ca2 activated k channels
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2006Co-Authors: Jafar Vatanparast, Mahyar Janahmadi, Alireza AsgariAbstract:Abstract Toxicity of paraoxon has been attributed to inhibition of cholinesterase, but little is known about its direct action on ionic channels. The effects of paraoxon (0.3 μM–0.6 μM) were studied on the firing behaviour of snail Neurones. Paraoxon significantly increased the frequency of spontaneously generated action potentials, shortened the afterhyperpolarization (AHP) and decreased the precision of firing. Short periods of high frequency-evoked trains of action potentials led to an accumulation in the depth and duration of post-train AHPs that was evidenced as an increase in time to resumption of autonomous activity. The delay time in autonomous activity initiation was linearly related to the frequency of spikes in the preceding train and the slope of the curve significantly decreased by paraoxon. The paraoxon induced hyperexcitability and its depressant effect on the AHP and the post-train AHP were not blocked by atropine and hexamethonium. Calcium spikes were elicited in a Na+ free Ringer containing voltage dependent potassium channel blockers. Paraoxon significantly decreased the duration of calcium spikes and following AHP and increased the frequency of spikes. These findings suggest that a reduction in calcium influx during action potential may decrease the activation of calcium dependent potassium channels that participate in AHP generation and act as a mechanism of paraoxon induced hyperexcitability.