scholarly journals Orexin depolarizes rat hypothalamic paraventricular nucleus neurons

2001 ◽  
Vol 281 (4) ◽  
pp. R1114-R1118 ◽  
Author(s):  
Tetsuro Shirasaka ◽  
Satoshi Miyahara ◽  
Takato Kunitake ◽  
Qing-Hua Jin ◽  
Kazuo Kato ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Brain Slices ◽  
Hypothalamic Paraventricular Nucleus ◽  
Dependent Manner ◽  
Patch Clamp Recording ◽  
Concentration Dependent Manner ◽  
Whole Cell Patch Clamp ◽  
Orexin Receptors ◽  
Bath Application

Orexins, also called hypocretins, are newly discovered hypothalamic peptides that are thought to be involved in various physiological functions. In spite of the fact that orexin receptors, especially orexin receptor 2, are abundant in the hypothalamic paraventricular nucleus (PVN), the effects of orexins on PVN neurons remain unknown. Using a whole cell patch-clamp recording technique, we investigated the effects of orexin-B on PVN neurons of rat brain slices. Bath application of orexin-B (0.01–1.0 μM) depolarized 80.8% of type 1 ( n = 26) and 79.2% of type 2 neurons tested ( n = 24) in the PVN in a concentration-dependent manner. The effects of orexin-B persisted in the presence of TTX (1 μM), indicating that these depolarizing effects were generated postsynaptically. Addition of Cd2+(1 mM) to artificial cerebrospinal fluid containing TTX (1 μM) significantly reduced the depolarizing effect in type 2 neurons. These results suggest that orexin-B has excitatory effects on the PVN neurons mediated via a depolarization of the membrane potential.

scholarly journals Neuropeptide FF and neuropeptide VF inhibit GABAergic neurotransmission in parvocellular neurons of the rat hypothalamic paraventricular nucleus

2007 ◽  
Vol 292 (5) ◽  
pp. R1872-R1880 ◽  
Author(s):  
Jack H. Jhamandas ◽  
Frédéric Simonin ◽  
Jean-Jacques Bourguignon ◽  
Kim H. Harris
Keyword(s):  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Inhibitory Input ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Gabaergic Neurotransmission ◽  
Whole Cell Patch Clamp ◽  
Neuropeptide Ff ◽  
Parvocellular Neurons ◽  
The Brain

Neuropeptide FF (NPFF) and neuropeptide VF (NPVF) are octapeptides belonging to the RFamide family of peptides that have been implicated in a wide variety of physiological functions in the brain, including central autonomic and neuroendocrine regulation. The effects of these peptides are mediated via NPFF1 and NPFF2 receptors that are abundantly expressed in the rat brain, including the hypothalamic paraventricular nucleus (PVN), an autonomic nucleus critical for the secretion of neurohormones and the regulation of sympathetic outflow. In this study, we examined, using whole cell patch-clamp recordings in the brain slice, the effects of NPFF and NPVF on inhibitory GABAergic synaptic input to parvocellular PVN neurons. Under voltage-clamp conditions, NPFF and NPVF reversibly and in a concentration-dependent manner reduced the evoked bicuculline-sensitive inhibitory postsynaptic currents (IPSCs) in parvocellular PVN neurons by 25 and 31%, respectively. RF9, a potent and selective NPFF receptor antagonist, blocked NPFF-induced reduction of IPSCs. Recordings of miniature IPSCs in these neurons following NPFF and NPVF applications showed a reduction in frequency but not amplitude, indicating a presynaptic locus of action for these peptides. Under current-clamp conditions, NPVF and NPFF caused depolarization (6–9 mV) of neurons that persisted in the presence of TTX but was abolished in the presence of bicuculline. Collectively, these data provide evidence for a disinhibitory role of NPFF and NPVF in the hypothalamic PVN via an attenuation of GABAergic inhibitory input to parvocellular neurons of this nucleus and explain the central autonomic effects of NPFF.

Leptin depolarizes rat hypothalamic paraventricular nucleus neurons

1998 ◽  
Vol 274 (5) ◽  
pp. R1468-R1472 ◽  
Author(s):  
Jeff E. Powis ◽  
Jaideep S. Bains ◽  
Alastair V. Ferguson
Keyword(s):  
Amino Acids ◽  
Feeding Behavior ◽  
Paraventricular Nucleus ◽  
Reversal Potential ◽  
Protein Product ◽  
Type I ◽  
Patch Clamp Recording ◽  
Cation Conductance ◽  
Bath Application ◽  
Membrane Effects

Leptin, the protein product of the ob/ obgene, is thought to have a central site of action, presumably within the hypothalamus, through which it regulates feeding behavior. The paraventricular nucleus (PVN) is one structure that has been implicated in regulating feeding behavior. Using patch-clamp recording techniques, this study examines the direct membrane effects of leptin on neurons in a coronal PVN slice. Bath application of the physiologically active leptin fragment (amino acids 22–56) elicited dose-related depolarizations in 82% of the type I cells tested ( n = 17) and 67% of the type II cells tested ( n = 9). By contrast, the physiologically inactive leptin fragment (amino acids 57–92) had no discernible effect on membrane potential ( n = 7). The effects of this peptide were unaffected following synaptic isolation of the cells by bath application of the sodium channel blocker tetrodotoxin ( n = 5). Voltage clamp recordings in six cells demonstrated that leptin increased a nonspecific cation conductance with a reversal potential near −30 mV. These findings suggest that neurons in PVN may play an important role in the central neuronal circuitry involved in the physiological response to leptin.

scholarly journals Cholecystokinin Octapeptide Increases Spontaneous Glutamatergic Synaptic Transmission to Neurons of the Nucleus Tractus Solitarius Centralis

2005 ◽  
Vol 94 (4) ◽  
pp. 2763-2771 ◽  
Author(s):  
V. Baptista ◽  
Z. L. Zheng ◽  
F. H. Coleman ◽  
R. C. Rogers ◽  
R. A. Travagli
Keyword(s):  
Receptor Antagonist ◽  
Nucleus Tractus Solitarius ◽  
Dependent Manner ◽  
Excitatory Effect ◽  
Concentration Dependent Manner ◽  
Whole Cell Patch Clamp ◽  
Glutamatergic Synaptic Transmission ◽  
Immunohistochemical Techniques ◽  
20 Nm ◽  
Brain Stem Slices

Cholecystokinin (CCK) is released from enteroendocrine cells after ingestion of nutrients and induces multiple effects along the gastrointestinal tract, including gastric relaxation and short-term satiety. We used whole cell patch-clamp and immunohistochemical techniques in rat brain stem slices to characterize the effects of CCK. In 45% of the neurons of nucleus tractus solitarius subnucleus centralis (cNTS), perfusion with the sulfated form of CCK (CCK-8s) increased the frequency of spontaneous excitatory currents (sEPSCs) in a concentration-dependent manner (1–300 nM). The threshold for the CCK-8s excitatory effect was 1 nM, the EC50 was 20 nM, and Emax was 100 nM. The excitatory effects of CCK-8s were still present when the slices were preincubated with tetrodotoxin or bicuculline or when the recordings were conducted with Cs+ electrodes. Pretreatment with the CCK-A receptor antagonist, lorglumide (1 μM), antagonized the effects of CCK-8s, whereas perfusion with the CCK-B preferring agonist CCK-8 nonsulfated (CCK-ns, 1 μM) did not affect the frequency of sEPSCs. Similarly, pretreatment with the CCK-B receptor antagonist, triglumide (1 μM), did not prevent the actions of CCK-8s. Although the majority (i.e., 76%) of CCK-8s unresponsive cNTS neurons had a bipolar somata shape and were TH-IR negative, no differences were found in either the morphological or the neurochemical phenotype of cNTS neurons responsive to CCK-8s. Our results suggest that the excitatory effects of CCK-8s on terminals impinging on a subpopulation of cNTS neurons are mediated by CCK-A receptors; these responsive neurons, however, do not have morphological or neurochemical characteristics that automatically distinguish them from nonresponsive neurons.

Riluzole Anesthesia

1996 ◽  
Vol 85 (3) ◽  
pp. 626-634. ◽  
Author(s):  
M. Bruce MacIver ◽  
Shanti M. Amagasu ◽  
Anthony A. Mikulec ◽  
Frances A. Monroe
Keyword(s):  
Butyric Acid ◽  
Brain Slices ◽  
Nerve Fibers ◽  
Dependent Manner ◽  
Gamma Amino Butyric Acid ◽  
General Anesthetic ◽  
Output Analysis ◽  
Concentration Dependent Manner ◽  
Paired Pulse ◽  
Amino Butyric Acid

Background Riluzole (RP 54274) is an experimental benzothiazole with anesthetic properties, but little is known about its synaptic or cellular actions. Methods The authors investigated riluzole effects on synaptic response of CA 1 pyramidal neurons in rat hippocampal brain slices. Electrophysiologic recordings of population spikes (PS), excitatory postsynaptic potentials (EPSP), and fiber volleys were studied. Paired pulse stimulation (120 ms interpulse interval) was used to measure effects on gamma-amino butyric acid (GABA)-mediated synaptic inhibition, and stimulus trains (33 Hz) were used to test for use-dependent effects. Results Synaptically evoked PS discharge was blocked in a concentration-dependent manner by riluzole (2.0-20 microM), similar to effects produced by other anesthetics. Paired pulse inhibition was not altered by riluzole. In contrast, 20 microM thiopental produced a marked increase in paired pulse inhibition. Riluzole (5.0 microM) produced a 46.6 +/- 19.8% depression of glutamate-mediated EPSPs, which could account for most of the mate-mediated EPSPs, which could account for most of the depression of PS discharge (54.2 +/- 12.6%) produced by this concentration. Riluzole produced a 36 +/- 17% depression of fiver volley amplitudes, which, based on input/output analysis, could completely account for the depression of EPSPs. The depression of fiber volley amplitudes showed a marked use-dependence; the second and subsequent action potentials in a train were progressively depressed by riluzole to a greater extent than the first action potential. Conclusions Riluzole produced a potent block of excitatory synaptic transmission via depression of presynaptic conduction in glutamatergic nerve fibers. The use-dependent depression observed resembled that produced by some local anesthetics on nerve conduction and sodium channels. The presynaptic action, together with a lack of effect on gamma-amino butyric acid-mediated inhibition, provides a unique mechanism of action for a general anesthetic.

Direct block of cloned hKv1.5 channel by cytochalasins, actin-disrupting agents

2005 ◽  
Vol 289 (2) ◽  
pp. C425-C436 ◽  
Author(s):  
Bok Hee Choi ◽  
Jung-Ah Park ◽  
Kyung-Ryoul Kim ◽  
Ggot-Im Lee ◽  
Yong-Tae Lee ◽  
...  
Keyword(s):  
Actin Filament ◽  
Cytochalasin B ◽  
Delayed Rectifier ◽  
Dependent Manner ◽  
Patch Clamp Technique ◽  
Independent Manner ◽  
Concentration Dependent Manner ◽  
Voltage Range ◽  
Whole Cell Patch Clamp ◽  
Voltage Dependent

The action of cytochalasins, actin-disrupting agents on human Kv1.5 channel (hKv1.5) stably expressed in Ltk− cells was investigated using the whole cell patch-clamp technique. Cytochalasin B inhibited hKv1.5 currents rapidly and reversibly at +60 mV in a concentration-dependent manner with an IC50 of 4.2 μM. Cytochalasin A, which has a structure very similar to cytochalasin B, inhibited hKv1.5 (IC50 of 1.4 μM at +60 mV). Pretreatment with other actin filament disruptors cytochalasin D and cytochalasin J, and an actin filament stabilizing agent phalloidin had no effect on the cytochalasin B-induced inhibition of hKv1.5 currents. Cytochalasin B accelerated the decay rate of inactivation for the hKv1.5 currents. Cytochalasin B-induced inhibition of the hKv1.5 channels was voltage dependent with a steep increase over the voltage range of the channel's opening. However, the inhibition exhibited voltage independence over the voltage range in which channels are fully activated. Cytochalasin B produced no significant effect on the steady-state activation or inactivation curves. The rate constants for association and dissociation of cytochalasin B were 3.7 μM/s and 7.5 s−1, respectively. Cytochalasin B produced a use-dependent inhibition of hKv1.5 current that was consistent with the slow recovery from inactivation in the presence of the drug. Cytochalasin B (10 μM) also inhibited an ultrarapid delayed rectifier K+ current ( IK,ur) in human atrial myocytes. These results indicate that cytochalasin B primarily blocks activated hKv1.5 channels and endogenous IK,ur in a cytoskeleton-independent manner as an open-channel blocker.

Mg2+ Inhibition of ATP-Activated Current in Rat Nodose Ganglion Neurons: Evidence That Mg2+ Decreases the Agonist Affinity of the Receptor

1997 ◽  
Vol 77 (6) ◽  
pp. 3391-3395 ◽  
Author(s):  
Chaoying Li ◽  
Robert W. Peoples ◽  
Forrest F. Weight
Keyword(s):  
Nodose Ganglion ◽  
Dependent Manner ◽  
Patch Clamp Technique ◽  
Concentration Dependent Manner ◽  
Agonist Affinity ◽  
Nodose Ganglion Neurons ◽  
Whole Cell Patch Clamp ◽  
Activation Rate ◽  
The Right ◽  
Ganglion Neurons

Li, Chaoying, Robert W. Peoples, and Forrest F. Weight. Mg2+ inhibition of ATP-activated current in rat nodose ganglion neurons: evidence that Mg2+ decreases the agonist affinity of the receptor. J. Neurophysiol. 77: 3391–3395, 1997. The effect of Mg2+ on ATP-activated current in rat nodose ganglion neurons was investigated with the use of the whole cell patch-clamp technique. Mg2+ decreased the amplitude of ATP-activated current in a concentration-dependent manner over the concentration range of 0.25–8 mM, with a 50% inhibitory concentration value of 1.5 mM for current activated by 10 μM ATP. Mg2+ shifted the ATP concentration-response curve to the right in a parallel manner, increasing the 50% effective concentration value for ATP from 9.2 μM in the absence of added Mg2+ to 25 μM in the presence of 1 mM Mg2+. Mg2+ increased the deactivation rate of ATP-activated current without changing its activation rate. The observations are consistent with an action of Mg2+ to inhibit ATP-gated ion channel function by decreasing the affinity of the agonist binding site on these receptors.

scholarly journals 11β-Hydroxysteroid Dehydrogenase Type 2 Activity in Hypothalamic Paraventricular Nucleus Modulates Sympathetic Excitation

Hypertension ◽  
2006 ◽  
Vol 48 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Zhi-Hua Zhang ◽  
Yu-Ming Kang ◽  
Yang Yu ◽  
Shun-Guang Wei ◽  
Thomas J. Schmidt ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Hydroxysteroid Dehydrogenase ◽  
Hypothalamic Paraventricular Nucleus

Synaptic Mechanisms of Thiopental-induced Alterations in Synchronized Cortical Activity

1996 ◽  
Vol 84 (6) ◽  
pp. 1425-1434 ◽  
Author(s):  
Heath S. Lukatch ◽  
Bruce M. MacIver
Keyword(s):  
Brain Slices ◽  
Afferent Input ◽  
Burst Suppression ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Patch Clamps ◽  
Concentration Dependent Manner ◽  
Direct Acting ◽  
Synaptic Mechanisms

Background Anesthetic depth after barbiturate administration has been correlated with distinct electroencephalogram (EEG) patterns. The current study used a rat neocortical brain slice micro-EEG preparation to investigate synaptic mechanisms underlying thiopental-induced transitions in synchronized neuronal activity. Methods Concentration-dependent cellular actions of thiopental were investigated in brain slices using specific pharmacologic probes, whole cell patch clamps, and extracellular field recordings. Theta-Like micro-EEG oscillations were elicited in neocortical slices by mimicking subcortical cholinergic and gamma-aminobutyric acid (GABA) afferent input with carbachol (100 microM), a cholinergic agonist, and bicuculline (10 microM) a GABAA antagonist. Results In the presence of 20 microM thiopental, micro-EEG slowing from theta (7.3 +/- 0.9 Hz, mean +/- SD, n = 19) to delta frequencies (2.5 +/- 0.5 Hz, n = 11) was associated with a threefold prolongation of inhibitory currents. Burst suppression activity occurred at 50 microM thiopental, and appeared to result from direct activation of GABAA-gated chloride currents, observed with voltage clamp recordings, and mimicked with a direct acting GABAA agonist, muscimol (1 microM). Isoelectric activity occurred at 100 microM thiopental, and likely resulted from reduced glutamatergic transmission, evidenced by depressed excitatory postsynaptic potentials. Glutamatergic excitation was required for burst suppression activity, because glutamate receptor antagonists blocked thiopental-induced bursts; forcing a transition to isoelectric activity. Conclusions Thiopental produced a continuum of EEG-like states in brain slices similar to those observed in vivo. The progression of thiopental-induced effects appear to have resulted from specific cellular actions that were recruited in a concentration-dependent manner. Progressive enhancement of synaptic inhibition followed by depression of excitatory transmission led to micro-EEG frequency slowing, burst suppression, and isoelectric activity.

Glutamatergic Synaptic Plasticity in the Periaqueductal Gray Governs Fear-induced Depression-like Behavior in Rats

2017 ◽  
Vol 41 (S1) ◽  
pp. S633-S633 ◽  
Author(s):  
Y.C. Ho ◽  
M.C. Hsieh ◽  
C.Y. Lai ◽  
H.Y. Peng
Keyword(s):  
Synaptic Transmission ◽  
Learned Helplessness ◽  
Depressive Disorders ◽  
Glutamate Release ◽  
Brain Slices ◽  
Periaqueductal Gray ◽  
Control Group ◽  
Patch Clamp Recording ◽  
Whole Cell Patch Clamp ◽  
Competing Interest

IntroductionMajor depressive disorder affecting more than 110 million people worldwide every year is a heterogeneous illness influenced by a variety of factors, including repeated stressful factors. Despite widely research during the past several decades, the pathophysiology and neurobiological mechanisms of depressive disorders remain unclear. Ventrolateral periaqueductal gray (vlPAG), a midbrain nucleus, has been considered as an important part of the circuitry that involves in stress-induced depression-like behaviors. Dysregulation of glutamatergic neurotransmission in depressed patients suggests that glutamate-mediated excitatory system is critical involved in the depressive disorders.ObjectivesIt is still unclear that whether vlPAG involves in fear condition-elicited depression-like behavior.AimsWe investigated the synaptic transmission in the vlPAG to examine whether vlPAG participates in fear-induced depression-like behavior in rats.MethodsDepression-like behaviors, in the rats, were induced by learned helplessness procedure. The synaptic transmission was conducted by whole-cell patch-clamp recording in the rat brain slices containing periaqueductal gray.ResultsRats receiving learned helplessness procedure displayed high failure rate in the escapable foot-shock test compared to control group. Both amplitude and frequency of miniature excitatory postsynaptic currents were significant reduced compared to control group, suggesting reduced presynaptic glutamate release and postsynaptic responses were involved in the learned helplessness procedure-induced depression behavior in rats.ConclusionsReduced glutamatergic transmission in the vlPAG contributes to learned helplessness procedure-induced depression-like behavior in rats through pre – and post-synaptic mechanisms.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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