scholarly journals Histamine-Induced Excitatory Responses in Mouse Ventromedial Hypothalamic Neurons: Ionic Mechanisms and Estrogenic Regulation

2007 ◽  
Vol 98 (6) ◽  
pp. 3143-3152 ◽  
Author(s):  
Jin Zhou ◽  
Anna W. Lee ◽  
Nino Devidze ◽  
Qiuyu Zhang ◽  
Lee-Ming Kow ◽  
...  
Keyword(s):  
Action Potential ◽  
Brain Slices ◽  
Histamine Receptor ◽  
Ventromedial Hypothalamus ◽  
Patch Clamp Recording ◽  
Action Potential Firing ◽  
Inward Current ◽  
Ovariectomized Mice ◽  
Ionic Mechanisms ◽  
The Impact

Histamine is capable of modulating CNS arousal states by regulating neuronal excitability. In the current study, histamine action in the ventromedial hypothalamus (VMH), its related ionic mechanisms, and its possible facilitation by estrogen were investigated using whole cell patch-clamp recording in brain slices from ovariectomized female mice. Under current clamp, a bath application of histamine (20 μM) caused membrane depolarization, associated with an increased membrane resistance. In some cells, the depolarization was accompanied by action potentials. Histamine application also significantly reduced the latency of action potential evoked by current steps. Histamine-induced depolarization was not affected by either tetrodotoxin or Cd2+. However, after blocking K+ channels with tetraethylammonium, 4-aminopyridine, and Cs+, depolarization was significantly decreased. Under voltage clamp, histamine-induced depolarization was associated with an inward current. The current–voltage relationship revealed that this inward current reversed near EK. The histamine effect was mimicked by a histamine receptor 1 (H1) agonist, but not a histamine receptor 2 (H2) agonist. An H1 antagonist, but not H2 antagonist, abolished histamine responses. When ovariectomized mice were treated with estradiol benzoate (E2), histamine-induced depolarization was significantly enhanced with an increased percentage of cells showing action potential firing. These results suggest that histamine depolarized VMH neurons by attenuating a K+ leakage current and this effect was mediated by H1 receptor. E2 facilitated histamine-induced excitation of VMH neurons. This histamine effect may present a potential mechanism by which estrogens modulate the impact of generalized CNS arousal on a sexual arousal–related neuronal group.

scholarly journals Intrinsic excitability varies by sex in prepubertal striatal medium spiny neurons

2015 ◽  
Vol 113 (3) ◽  
pp. 720-729 ◽  
Author(s):  
David M. Dorris ◽  
Jinyan Cao ◽  
Jaime A. Willett ◽  
Caitlin A. Hauser ◽  
John Meitzen
Keyword(s):  
Sex Differences ◽  
Action Potential ◽  
Firing Rate ◽  
Drugs Of Abuse ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Medium Spiny Neuron ◽  
Action Potential Firing ◽  
Electrophysiological Properties

Sex differences in neuron electrophysiological properties were traditionally associated with brain regions directly involved in reproduction in adult, postpubertal animals. There is growing acknowledgement that sex differences can exist in other developmental periods and brain regions as well. This includes the dorsal striatum (caudate/putamen), which shows robust sex differences in gene expression, neuromodulator action (including dopamine and 17β-estradiol), and relevant sensorimotor behaviors and pathologies such as the responsiveness to drugs of abuse. Here we examine whether these sex differences extend to striatal neuron electrophysiology. We test the hypothesis that passive and active medium spiny neuron (MSN) electrophysiological properties in prepubertal rat dorsal striatum differ by sex. We made whole cell recordings from male and females MSNs from acute brain slices. The slope of the evoked firing rate to current injection curve was increased in MSNs recorded from females compared with males. The initial action potential firing rate was increased in MSNs recorded from females compared with males. Action potential after-hyperpolarization peak was decreased, and threshold was hyperpolarized in MSNs recorded from females compared with males. No sex differences in passive electrophysiological properties or miniature excitatory synaptic currents were detected. These findings indicate that MSN excitability is increased in prepubertal females compared with males, providing a new mechanism that potentially contributes to generating sex differences in striatal-mediated processes. Broadly, these findings demonstrate that sex differences in neuron electrophysiological properties can exist prepuberty in brain regions not directly related to reproduction.

scholarly journals D2-Like Dopamine Receptors Modulate SKCa Channel Function in Subthalamic Nucleus Neurons Through Inhibition of Cav2.2 Channels

2008 ◽  
Vol 99 (2) ◽  
pp. 442-459 ◽  
Author(s):  
Sankari Ramanathan ◽  
Tatiana Tkatch ◽  
Jeremy F. Atherton ◽  
Charles J. Wilson ◽  
Mark D. Bevan
Keyword(s):  
Action Potential ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Subthalamic Nucleus ◽  
Brain Slices ◽  
Receptor Activation ◽  
Functional Coupling ◽  
Channel Blockers ◽  
Dopamine Depletion ◽  
Patch Clamp Recording

The activity patterns of subthalamic nucleus (STN) neurons are intimately related to motor function/dysfunction and modulated directly by dopaminergic neurons that degenerate in Parkinson's disease (PD). To understand how dopamine and dopamine depletion influence the activity of the STN, the functions/signaling pathways/substrates of D2-like dopamine receptors were studied using patch-clamp recording. In rat brain slices, D2-like dopamine receptor activation depolarized STN neurons, increased the frequency/irregularity of their autonomous activity, and linearized/enhanced their firing in response to current injection. Activation of D2-like receptors in acutely isolated neurons reduced transient outward currents evoked by suprathreshold voltage steps. Modulation was inhibited by a D2-like receptor antagonist and occluded by voltage-dependent Ca2+ (Cav) channel or small-conductance Ca2+-dependent K+ (SKCa) channel blockers or Ca2+-free media. Because Cav channels are targets of Gi/o-linked receptors, actions on step- and action potential waveform-evoked Cav channel currents were studied. D2-like receptor activation reduced the conductance of Cav2.2 but not Cav1 channels. Modulation was mediated, in part, by direct binding of Gβγ subunits because it was attenuated by brief depolarization. D2 and/or D3 dopamine receptors may mediate modulation because a D4-selective agonist was ineffective and mRNA encoding D2 and D3 but not D4 dopamine receptors was detectable. Brain slice recordings confirmed that SKCa channel-mediated action potential afterhyperpolarization was attenuated by D2-like dopamine receptor activation. Together, these data suggest that D2-like dopamine receptors potently modulate the negative feedback control of firing that is mediated by the functional coupling of Cav2.2 and SKCa channels in STN neurons.

α5GABAA Receptors Regulate the Intrinsic Excitability of Mouse Hippocampal Pyramidal Neurons

2007 ◽  
Vol 98 (4) ◽  
pp. 2244-2254 ◽  
Author(s):  
Robert P. Bonin ◽  
Loren J. Martin ◽  
John F. MacDonald ◽  
Beverley A. Orser
Keyword(s):  
Action Potential ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Physiological Role ◽  
Network Activity ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Action Potential Firing ◽  
Membrane Hyperpolarization ◽  
Hippocampal Pyramidal Neurons

GABAA receptors generate both phasic and tonic forms of inhibition. In hippocampal pyramidal neurons, GABAA receptors that contain the α5 subunit generate a tonic inhibitory conductance. The physiological role of this tonic inhibition is uncertain, although α5GABAA receptors are known to influence hippocampal-dependent learning and memory processes. Here we provide evidence that α5GABAA receptors regulate the strength of the depolarizing stimulus that is required to generate an action potential in pyramidal neurons. Neurons from α5 knock-out (α5−/−) and wild-type (WT) mice were studied in brain slices and cell cultures using whole cell and perforated-patch-clamp techniques. Membrane resistance was 1.6-fold greater in α5−/− than in WT neurons, but the resting membrane potential and chloride equilibrium potential were similar. Membrane hyperpolarization evoked by an application of exogenous GABA was greater in WT neurons. Inhibiting the function of α5GABAA receptor with nonselective (picrotoxin) or α5 subunit-selective (L-655,708) compounds depolarized WT neurons by ∼3 mV, whereas no change was detected in α5−/− neurons. The depolarizing current required to generate an action potential was twofold greater in WT than in α5−/− neurons, whereas the slope of the input-output relationship for action potential firing was similar. We conclude that shunting inhibition mediated by α5GABAA receptors regulates the firing of action potentials and may synchronize network activity that underlies hippocampal-dependent behavior.

Contribution of the low-threshold T-type calcium current in generating the post-spike depolarizing afterpotential in dentate granule neurons of immature rats

1993 ◽  
Vol 70 (1) ◽  
pp. 223-231 ◽  
Author(s):  
L. Zhang ◽  
T. A. Valiante ◽  
P. L. Carlen
Keyword(s):  
Action Potential ◽  
Strong Dependence ◽  
Brain Slices ◽  
Membrane Resistance ◽  
Membrane Hyperpolarization ◽  
Single Action ◽  
Bath Application ◽  
Immature Rats ◽  
Ionic Mechanisms ◽  
Inward Currents

1. The underlying ionic mechanisms of the postspike depolarizing afterpotential (DAP) in hippocampal dentate granule (DG) neurons of immature rats (postnatal 7- to 17-day-old) were examined using whole cell patch recordings in brain slices. 2. In current-clamp mode, the DAP followed each single action potential. Graded DAP-like responses were also evoked by depolarizing current pulses when the action potential was blocked by tetrodotoxin (TTX), demonstrating that the TTX-sensitive Na+ conductance is not necessary for DAP generation. The membrane resistance near the DAP peak was lower than at rest, suggesting activation of inward currents rather than blockade of outward currents during the DAP. The DAP peak amplitude showed a strong dependence on voltage, increasing with membrane hyperpolarization and decreasing with depolarization in the range of -90 to -50 mV. Repetitive stimulation at 1-2 Hz did not change the amplitude or decay of the DAP or DAP-like response. 3. Bath application of 2 mM 4-aminopyridine (4-AP) and 5 mM tetraethylammonium chloride (TEA) prolonged the action potential and enhanced the DAP, suggesting that the DAP waveform is determined by the interaction of voltage-activated outward K+ currents and inward currents. 4. Bath application of 2 mM Co2+ depressed the DAP and the DAP-like potential. Replacement of extracellular Ca2+ with Ba2+ potentiated the DAP. Intracellular Ca2+ chelation with the fast chelator, bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), only slightly enhanced the DAP, suggesting that the DAP is not generated by inward currents activated secondary to Ca2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Excitatory GABAergic modulation of calyx terminals in the vestibular sensory end organ

2020 ◽  
Author(s):  
Yugandhar Ramakrishna ◽  
Soroush G. Sadeghi
Keyword(s):  
Action Potential ◽  
Gaba Receptors ◽  
Extracellular Fluid ◽  
Potassium Currents ◽  
Spontaneous Discharge ◽  
Sprague Dawley ◽  
Patch Clamp Recording ◽  
Excitatory Effect ◽  
Action Potential Firing ◽  
Single Action

ABSTRACTGABAergic sources have been identified in the vestibular sensory neuroepithelium, mainly in the supporting cells. However, existence of GABA receptors or any possible GABAergic effects on vestibular nerve afferents has not been investigated. The current study was conducted to determine whether activation of GABA-B receptors affects calyx afferent terminals in the central region of the cristae of the semicircular canals in rats. We used patch clamp recording in P13 – P18 Sprague-Dawley rats of either sex. Application of GABA-B receptor agonist baclofen inhibited voltage activated outward potassium currents. This effect was blocked by selective GABA-B receptor antagonist CGP 35348. Antagonists of small (SK) and large (BK) current potassium channels resulted in an almost complete block of baclofen effect. The remaining baclofen effect was due to inhibition of voltage gated calcium channels and was blocked by cadmium chloride. Furthermore, baclofen had no effect in the absence of calcium in the extracellular fluid. Inhibition of potassium currents by GABA-B activation resulted in an excitatory effect on calyx terminal action potential firing. While in the control condition calyces could only fire a single action potential during step depolarizations, in the presence of baclofen they fired continuously during steps and a few even showed spontaneous discharge. We also found a decrease in threshold for action potential generation and a decrease in first spike latency during step depolarization. These results provide the first evidence for the presence of GABA-B receptors on calyx terminals, show that their activation results in an unusual excitatory effect and that GABA inputs could be used to modulate calyx response properties.

scholarly journals Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

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 The thalamic low-threshold Ca 2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks

2011 ◽  
Vol 369 (1952) ◽  
pp. 3820-3839 ◽  
Author(s):  
Vincenzo Crunelli ◽  
Adam C. Errington ◽  
Stuart W. Hughes ◽  
Tibor I. Tóth
Keyword(s):  
Action Potential ◽  
Slow Oscillation ◽  
Global Dynamics ◽  
Action Potential Firing ◽  
Local And Global Dynamics ◽  
Up States ◽  
Potential Firing ◽  
Low Threshold

During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca 2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca 2+ signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.

scholarly journals Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents

2013 ◽  
Vol 304 (10) ◽  
pp. G908-G916 ◽  
Author(s):  
Shizhong Zhang ◽  
Gintautas Grabauskas ◽  
Xiaoyin Wu ◽  
Moon Kyung Joo ◽  
Andrea Heldsinger ◽  
...  
Keyword(s):  
Mast Cell ◽  
Action Potential ◽  
Cell Activation ◽  
Vagal Afferents ◽  
Mast Cell Activation ◽  
Lipid Mediator ◽  
Prostaglandin D2 ◽  
Patch Clamp Recording ◽  
C Fibers ◽  
Ganglion Neurons

Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal distension were compared before and after perfusion of PGD2, DP1 and DP2 receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2 on 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1 and DP2 receptor mRNA and protein were expressed mainly in small- and medium-diameter neurons in nodose ganglia. PGD2 significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1 receptor agonist BW 245C mimicked this effect. PGD2 directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1 receptor antagonist BW A868C significantly inhibited PGD2 perfusion- or MC activation-induced increases in esophageal distension-evoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2 plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization.

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