Frequency Of Spike Discharges Research Articles

[A comparative study of microwire electrode array with built-in and external reference electrodes].

Objective: To compare the difference between the built-in and external reference electrode of microwire electrode array in the process of recording rat brain neuron firings, optimizing the production and embedding of the microwire electrode array, and providing a more affordable and excellent media tool for multi-channel electrophysiological real-time recording system. Methods: A 16 channel microwire electrode array was made by using nickel chromium alloy wires, circuit board, electrode pin and ground wires (silver wires). The reference electrode of the microwire electrode array was built-in (the reference electrode and electrode array were arranged in parallel) or external (the reference electrode and ground wire were welded at both ends of one side of the electrode), and the difference between the two electrodes was observed and compared in recording neuronal discharges in ACC brain area of rats. Experimental rats were divided into built-in group and external group, n=8-9. The test indicators included signal-to-noise ratio (n=8), discharge amplitude (n=380) and discharge frequency (n=54). Results: The microwire electrode array with both built-in and external reference electrodes successfully recorded the electrical signals of neurons in the ACC brain region of rats. Compared with the external group, the electrical signals of neurons in built-in group had the advantages of a higher signal-to-noise ratio (P＜0.05), a smaller amplitude of background signals and less noise interference, and a larger discharge amplitude(P＜0.05); there was no significant difference in spike discharge frequency recorded by these two types of electrodes (P＞0.05). Conclusion: When recording the electrical activity of neurons in the ACC brain region of rats, the microwire electrode array with built-in reference electrode recorded electrical signals with higher signal-to-noise ratio and larger discharge amplitude, providing a more reliable tool for multi-channel electrophysiology technology.

Ionic channel blockage in stochastic Hodgkin-Huxley neuronal model driven by multiple oscillatory signals.

Ionic channel blockage and multiple oscillatory signals play an important role in the dynamical response of pulse sequences. The effects of ionic channel blockage and ionic channel noise on the discharge behaviors are studied in Hodgkin-Huxley neuronal model with multiple oscillatory signals. It is found that bifurcation points of spontaneous discharge are altered through tuning the amplitude of multiple oscillatory signals, and the discharge cycle is changed by increasing the frequency of multiple oscillatory signals. The effects of ionic channel blockage on neural discharge behaviors indicate that the neural excitability can be suppressed by the sodium channel blockage, however, the neural excitability can be reversed by the potassium channel blockage. There is an optimal blockage ratio of potassium channel at which the electrical activity is the most regular, while the order of neural spike is disrupted by the sodium channel blockage. In addition, the frequency of spike discharge is accelerated by increasing the ionic channel noise, the firing of neuron becomes more stable if the ionic channel noise is appropriately reduced. Our results might provide new insights into the effects of ionic channel blockages, multiple oscillatory signals, and ionic channel noises on neural discharge behaviors.

Functional Coupling of K+-Cl- Cotransporter (KCC) to GABA-Gated Cl- Channels in the Central Nervous System of Drosophila melanogaster Leads to Altered Drug Sensitivities.

GABAergic signaling is the cornerstone for fast synaptic inhibition of neural signaling in arthropods and mammals and is the molecular target for insecticides and pharmaceuticals, respectively. The K+-Cl- cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular Cl- concentration, yet the fundamental physiology, comparative physiology, and toxicological relevance of insect KCC is understudied. Considering this, we employed electrophysiological, genetic, and pharmacological methods to characterize the physiological underpinnings of KCC function to the Drosophila CNS. Our data show that genetic ablation or pharmacological inhibition of KCC results in an increased spike discharge frequency and significantly ( P < 0.05) reduces the CNS sensitivity to γ-aminobutyric acid (GABA). Further, simultaneous inhibition of KCC and ligand-gated chloride channel (LGCC) complex results in a significant ( P < 0.001) increase in CNS spontaneous activity over baseline firing rates that supports functional coupling of KCC to LGCC function. Interestingly, 75% reduction in KCC mRNA did not alter basal neurotransmission levels indicating that only a fraction of the KCC population is required to maintain the Cl- ionic gradient when at rest, but prolonged synaptic activity increases the threshold for GABA-mediated inhibition and reduces nerve sensitivity to GABA. These data expand current knowledge regarding the physiological role of KCC in a model insect and provides the necessary foundation to develop KCC as a novel biochemical target of insecticides, as well as complements existing research to provide a holistic understanding of the plasticity in mammalian health and disease.

Inwardly Rectifying Potassium (Kir) Channels Represent a Critical Ion Conductance Pathway in the Nervous Systems of Insects

A complete understanding of the physiological pathways critical for proper function of the insect nervous system is still lacking. The recent development of potent and selective small-molecule modulators of insect inward rectifier potassium (Kir) channels has enabled the interrogation of the physiological role and toxicological potential of Kir channels within various insect tissue systems. Therefore, we aimed to highlight the physiological and functional role of neural Kir channels the central nervous system, muscular system, and neuromuscular system through pharmacological and genetic manipulations. Our data provide significant evidence that Drosophila neural systems rely on the inward conductance of K+ ions for proper function since pharmacological inhibition and genetic ablation of neural Kir channels yielded dramatic alterations of the CNS spike discharge frequency and broadening and reduced amplitude of the evoked EPSP at the neuromuscular junction. Based on these data, we conclude that neural Kir channels in insects (1) are critical for proper function of the insect nervous system, (2) represents an unexplored physiological pathway that is likely to shape the understanding of neuronal signaling, maintenance of membrane potentials, and maintenance of the ionic balance of insects, and (3) are capable of inducing acute toxicity to insects through neurological poisoning.

A Novel Compound Targeting Kv7.2/3 Channels Relieves Inflammatory and Neuropathic Pain

Encoded by Kv7.2/Kv7.3 subunit assembly, M-channels generate sub-threshold voltage-gated K+ currents that regulate neuronal excitability. Inour quest to target neuronal M-channels, we previously designed noveldiphenylamine carboxylates that are powerful Kv7.2 channel openers. These drugs stabilize the Kv7.2 channel open state by interacting with its voltage sensing domain (VSD). Using the same structural framework, we designed a novel molecule, NH34, to test its activity on neuronal excitability and probe its potency in vivo on inflammatory and neuropathic pain. In transfected CHO cells, NH34 significantly increased Kv7.2 currents, by producing a hyperpolarizing voltage shift of the activation curve (EC50 = 17.5 µM). Interestingly, two S4 mutants, R198A and R207W significantly decreased the opener potency of the drug, suggesting that NH34, like NH29, may interact with the VSD of Kv7.2. NH34 preferentially acts as an opener of Kv7.2 and Kv7.3 channels. NH34 was ineffective on Kv7.4 and Kv7.5 but produced a significant inhibition of TRPV1 cation channels. In CA1 pyramidal neurons from rat hippocampal slices, NH34 reduced the spike discharge frequency evoked by injection of depolarizing current. NH34 significantly depressed the slope of field epsp and the fiber volley amplitude recorded extracellularly in the CA1 pyramidal region following stimulation of the Schaeffer collaterals. NH34 reduced the frequency of evoked spike discharge in dorsal root ganglion neurons. In vivo, NH34 (3-30 mg/kg p.o) significantly relieved the hyperalgesia evoked by mechanical pressure of the paw in a rat model of inflammatory pain. Similarly, NH34 (3-30 mg/kg p.o) was very efficient in alleviating the hyperalgesia evoked by mechanical pressure or cold allodynia in a Seltzer rat model of neuropathic pain. In all, the data suggest that NH34 is a very promising drug template for treating inflammatory and neuropathic pain.

Multifaceted Modulation of K+ Channels by Protein-tyrosine Phosphatase ϵ Tunes Neuronal Excitability

Non-receptor-tyrosine kinases (protein-tyrosine kinases) and non-receptor tyrosine phosphatases (PTPs) have been implicated in the regulation of ion channels, neuronal excitability, and synaptic plasticity. We previously showed that protein-tyrosine kinases such as Src kinase and PTPs such as PTPα and PTPε modulate the activity of delayed-rectifier K(+) channels (I(K)). Here we show cultured cortical neurons from PTPε knock-out (EKO) mice to exhibit increased excitability when compared with wild type (WT) mice, with larger spike discharge frequency, enhanced fast after-hyperpolarization, increased after-depolarization, and reduced spike width. A decrease in I(K) and a rise in large-conductance Ca(2+)-activated K(+) currents (mBK) were observed in EKO cortical neurons compared with WT. Parallel studies in transfected CHO cells indicate that Kv1.1, Kv1.2, Kv7.2/7.3, and mBK are plausible molecular correlates of this multifaceted modulation of K(+) channels by PTPε. In CHO cells, Kv1.1, Kv1.2, and Kv7.2/7.3 K(+) currents were up-regulated by PTPε, whereas mBK channel activity was reduced. The levels of tyrosine phosphorylation of Kv1.1, Kv1.2, Kv7.3, and mBK potassium channels were increased in the brain cortices of neonatal and adult EKO mice compared with WT, suggesting that PTPε in the brain modulates these channel proteins. Our data indicate that in EKO mice, the lack of PTPε-mediated dephosphorylation of Kv1.1, Kv1.2, and Kv7.3 leads to decreased I(K) density and enhanced after-depolarization. In addition, the deficient PTPε-mediated dephosphorylation of mBK channels likely contributes to enhanced mBK and fast after-hyperpolarization, spike shortening, and consequent increase in neuronal excitability observed in cortical neurons from EKO mice.

Response properties of periodontal mechanosensitive neurons in the trigeminal ganglion of rabbit and neuronal activities during grinding-like jaw movement induced by cortical stimulation

Objective To examine the response properties of incisor- and molar-sensitive periodontal mechanosensitive (PM) neurons in the trigeminal ganglion of rabbit and the activities of the molar-sensitive PM neurons during the grinding-like jaw movement. Design Discharges of PM units were recorded from the trigeminal ganglion with a microelectrode. The grinding-like jaw movement was induced by repetitive electrical stimulation of the cortical masticatory area. Results Upper-incisor (UI) and upper-molar (UM) units were recorded from the rostromedial area of the trigeminal ganglion, and lower-incisor (LI) and lower-molar (LM) units were distributed in the caudolateral area. Most PM units were responsive to only one tooth, slowly adapting ones and responded to tooth stimulation of a force of less than 0.05 N. The optimal stimulus direction for most UI units was labio-lingual, axial or linguo-labial, and that for most LI units was linguo-labial or axial. The optimal stimulus direction of anterior UM and LM units was oriented predominantly mesio-distal or axial. The maximum frequency of spike discharges for UM units for which the optimal stimulus direction was axial or bucco-lingual was in the middle period of the grinding phase. However, UM units for which the optimal stimulus direction was mesio-distal or linguo-buccal were fired mostly in the early period. Conclusions Periodontal sensory information in the grinding phase of jaw movement is transmitted by PM neurons with various response properties encoding the magnitude and direction of a force at least, in a weaker range of force than a saturating response level.

Stromal cell‐derived factor‐1α directly modulates voltage‐dependent currents of the action potential in mammalian neuronal cells

Stromal cell-derived factor-1alpha (SDF-1alpha) is a chemokine whose receptor, CXCR4, is distributed in specific brain areas including hypothalamus. SDF-1alpha has recently been found to play important roles in neurons, although direct modulation of voltage-gated ionic channels has never been shown. In order to clarify this issue, we performed patch-clamp experiments in fetal mouse hypothalamic neurons in culture. SDF-1alpha (10 nm) decreased the peak and rising slope of the action potentials and spike discharge frequency in 22% of hypothalamic neurons tested. This effect was blocked by the CXCR4 antagonist AMD 3100 (1 microm) but not by the metabotropic glutamate receptor antagonist MCPG (500 microm), indicating a direct action of SDF-1alpha on its cognate receptor. This effect involved a depression of both inward and outward voltage-dependent currents of the action potential. We confirmed these effects in the human neuroblastoma cell line SH-SY5Y, which endogenously expresses CXCR4. Voltage-clamp experiments revealed that SDF-1alpha induced a 20% decrease in the peak of the tetrodotoxin-sensitive sodium current and tetraethylammonium-sensitive delayed rectifier potassium current, respectively. Both effects were concentration dependent, and blocked by AMD 3100 (200 nm). This dual effect was reduced or blocked by 0.4 mm GTPgammaS G-protein pre-activation or by pre-treatment with the G-protein inhibitor pertussis toxin (200 ng/mL), suggesting that it is mediated via activation of a G(i/o) protein. This study extends the functions of SDF-1alpha to a direct modulation of voltage-dependent membrane currents of neuronal cells.

Opioids inhibit lateral amygdala pyramidal neurons by enhancing a dendritic potassium current.

Pyramidal neurons in the lateral amygdala discharge trains of action potentials that show marked spike frequency adaptation, which is primarily mediated by activation of a slow calcium-activated potassium current. We show here that these neurons also express an alpha-dendrotoxin- and tityustoxin-Kalpha-sensitive voltage-dependent potassium current that plays a key role in the control of spike discharge frequency. This current is selectively targeted to the primary apical dendrite of these neurons. Activation of micro-opioid receptors by application of morphine or d-Ala(2)-N-Me-Phe(4)-Glycol(5)-enkephalin (DAMGO) potentiates spike frequency adaptation by enhancing the alpha-dendrotoxin-sensitive potassium current. The effects of micro-opioid agonists on spike frequency adaptation were blocked by inhibiting G-proteins with N-ethylmaleimide (NEM) and by blocking phospholipase A(2). Application of arachidonic acid mimicked the actions of DAMGO or morphine. These results show that micro-opioid receptor activation enhances spike frequency adaptation in lateral amygdala neurons by modulating a voltage-dependent potassium channel containing Kv1.2 subunits, through activation of the phospholipase A(2)-arachidonic acid-lipoxygenases cascade.

Electrophysiological classes of cat primary visual cortical neurons in vivo as revealed by quantitative analyses.

To facilitate the characterization of cortical neuronal function, the responses of cells in cat area 17 to intracellular injection of current pulses were quantitatively analyzed. A variety of response variables were used to separate the cells into subtypes using cluster analysis. Four main classes of neurons could be clearly distinguished: regular spiking (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH). Each of these contained significant subclasses. RS neurons were characterized by trains of action potentials that exhibited spike frequency adaptation. Morphologically, these cells were spiny stellate cells in layer 4 and pyramidal cells in layers 2, 3, 5, and 6. FS neurons had short-duration action potentials (<0.5 ms at half height), little or no spike frequency adaptation, and a steep relationship between injected current intensity and spike discharge frequency. Morphologically, these cells were sparsely spiny or aspiny nonpyramidal cells. IB neurons typically generated a low frequency (<425 Hz) burst of spikes at the beginning of a depolarizing current pulse followed by a tonic train of action potentials for the remainder of the pulse. These cells were observed in all cortical layers, but were most abundant in layer 5. Finally, CH neurons generated repetitive, high-frequency (350-700 Hz) bursts of short-duration (<0.55 ms) action potentials. Morphologically, these cells were layer 2-4 (mainly layer 3) pyramidal or spiny stellate neurons. These results indicate that firing properties do not form a continuum and that cortical neurons are members of distinct electrophysiological classes and subclasses.

The in vivo relevance of the varied channel-blocking properties of uncompetitive NMDA antagonists: tests on spinal neurones

The voltage dependence and channel-blocking kinetics of uncompetitive NMDA receptor antagonists have been well-described using in vitro techniques, but there is little evidence concerning the functional significance of these properties in vivo. We have now compared the effects of NMDA antagonists that display varied profiles of voltage-dependent block in vitro, on responses of spinal neurones in anaesthetised rats. The compounds examined were the uncompetitive channel blockers memantine, ketamine and MK-801 and, for comparison, an antagonist that acts at the strychnine-insensitive glycine binding site (MRZ 2/502). Using frequency of spike discharge as an indicator of somatic depolarisation, we have compared the effects of these antagonists on responses evoked by iontophoretic NMDA application and on synaptic responses evoked by pinch or electrical stimulation (the latter eliciting “wind-up”). The effectiveness of the antagonists was directly but variably related to the discharge frequency of the test response. The rank order of dependence on firing rate matched the rank order of voltage dependence reported in vitro, namely: memantine > ketamine > MK-801≥ MRZ 2/502. Doses that reduced responses to iontophoretic application of NMDA were less effective at reducing responses to pinch, perhaps due to the major non-NMDA component of the synaptic response. Memantine preferentially reduced “wind-up” relative to responses to pinch, whereas ketamine and MK-801 reduced both types of synaptic responses in parallel. This “filtering” by low affinity, voltage-dependent NMDA antagonists such as memantine, of non-physiological activity whilst leaving normal synaptic events relatively untouched, may contribute to their more favourable clinical profile.

Effects of Y-26763, A Novel K-Channel Opener, on Electrical Responses of Smooth Muscles in the Guinea Pig Bladder

Purpose The effects of Y-26763, a novel K-channel opener, on spontaneous and carbachol-induced electrical responses of bladder smooth muscle in guinea pig were studied. Material and Methods Intracellular microelectrodes were used to record membrane electrical responses from the detrusor smooth muscle of guinea pig. Results In most cells studied, the membranes were spontaneously active with continuous or periodic bursts of spike discharge which were sensitive to nicardipine, a Ca sup ++ -antagonist. Y-26763 inhibited the spike discharges with or without hyperpolarization of the membrane; the spike inhibition appeared to lower concentrations (greater than 10 sup -8 M.) than the hyperpolarization (greater than 10 sup -7 M.). The effects of Y-26763 were antagonized by glibenclamide, which suggested an involvement of ATP-sensitive K-channels. Carbachol increased the discharge frequency of spikes, with (greater than 10 sup -6 M.) or without (greater than 10 sup -7 M.) depolarization of the membrane. Y-26763 (greater than 10 sup -7 M.) inhibited the spike generation but not the depolarization induced by carbachol (10 sup -6 M.) in a concentration-dependent manner. Conclusion Y-26763 may directly prevent electrical excitability of bladder smooth muscles by inhibiting spike discharges and also by hyperpolarizing the membrane. The results suggest that this K-channel opener could have clinical applications for the treatment of unstable bladders.

Effect of portal infusion of hypertonic saline on neurons in the dorsal motor nucleus of the vagus in the rat

Effects of hepatoportal osmo-receptive (or sodium-receptive) afferents on neurons within the dorsal motor nucleus of the vagus (DMV) were investigated electrophysiologically in urethane-chloralose anesthetized rats. Responses of 56 spontaneously active neurons to antidromic stimulation of the ventral trunk of the subdiaphragmatic vagus were recorded in the left DMV. Among them, 35 neurons were inhibited by electrical stimulation of the hepatic branch of the vagus nerve (inhibitory neurons), except two neurons that were slightly excited. Effects of portal infusion of 3.6% NaCl were examined on 26 inhibitory neurons. Sixteen neurons increased their discharge rates and one neuron decreased its discharge rate in response to portal infusion of hypertonic saline. Thirty-five DMV neurons responded to electrical stimulation of the dorsal trunk of the subdiaphragmatic vagus were inhibited by electrical stimulation of the hepatic branch of the vagus. Four neurons were excited by this stimulation. Relatively smaller number of neurons (5 out of 22 inhibitory neurons) increased their discharge rates in response to portal infusion of hypertonic saline. In conclusion, the response of DMV neuron observed in this experiment was characterized by increasing the frequency of spike discharges in response to portal infusion of hypertonic saline. However, these neurons were inhibited by electrical stimulation of the hepatic branch of the vagus nerve. These results suggest that the hepatoportal osmoreceptive afferents may be conveyed to the DMV via inhibitory synapses.

Hypoxia-induced functional alterations in adult rat neocortex.

1. Brief periods of hypoxia (2-7 min) were induced in rat neocortical slices maintained in an interface-type recording chamber at 34-35 degrees C by changing the aerating gas from 95% O2-5% CO2 to 95% N2-5% CO2. Field potential (FP) and intracellular recordings were obtained in layers II/III of primary somatosensory cortex. Intracellular injection of biocytin revealed the characteristic morphology of supragranular spiny pyramidal neurons. 2. Excitatory synaptic transmission reversibly decreased by 45% as estimated from FP responses to orthodromic stimulation of the underlying white matter/layer VI. Excitatory postsynaptic potentials (EPSPs) were suppressed by 36% in amplitude and recovered within 2-3 min after reoxygenation. During the recovery period, EPSPs showed a reversible increase in duration by 72%. 3. Inhibitory synaptic transmission was completely blocked as determined in FP responses with a paired-pulse inhibition protocol. The fast inhibitory postsynaptic potential (IPSP) declined by 58% during hypoxia. The long-lasting IPSP was suppressed by 75% and showed incomplete recovery. During hypoxia, the amplitude of both IPSPs was significantly more strongly suppressed than the EPSP. 4. In 40% of the cells, hypoxia induced an early anoxic hyperpolarization with a reversal potential of E = -80.8 mV, followed by a postanoxic hyperpolarization (E = -89.4 mV). In a second group of cells (37%), a gradual anoxic depolarization with E = -57.5 mV was observed instead of an early hyperpolarization. In both groups of cells, the anoxic response was associated with a marked decrease in input resistance, by 42 and 31%, respectively. 5. The spike discharge frequency was reversibly suppressed by 71% during hypoxia. A transient hyperexcitability accompanied with a rise in input resistance and discharge rate was observed in 38% of the cells on reoxygenation. 6. The reversal potential of the anoxic hyperpolarization was unaffected by tetrodotoxin (TTX) but was significantly altered by application of the ATP-sensitive K+ channel (KATP) blocker gliquidone. Application of gliquidone additionally resulted in a significantly smaller hypoxia-induced decline in paired-pulse inhibition. 7. Increases in tissue high-energy phosphates induced by preincubating the slices in 25 mM creatine for greater than 2 h had a pronounced protective effect on excitatory and inhibitory synaptic transmission. 8. These data suggest a selective vulnerability of the neocortical inhibitory system during hypoxia. Our results further indicate that hypoxia activates a pre- and postsynaptic KATP conductance because of the decline in intracellular ATP.

Intracellular injection of apamin reduces a slow potassium current mediating afterhyperpolarizations and IPSPs in neocortical neurons of cats

Electrophysiologic effects of intracellularly injected apamin, a Ca 2+-dependent K + channel blocker, were investigated in neurons of the motor cortex of awake cats. Single-electrode voltage clamp techniques were used to measure changes in membrane currents including those that were synaptically activated. All changes occured within 2–4 min after pressure injection of apamin with partial recovery observed within 8–15 min. Apamin selectively abolished an outward current that mediated a slow afterhyperpolarization (AHP) following intracellular depolarizing current pulses and action potentials without influencing the time course of the action potentials or an associated fast AHP component. In addition apamin increased the number and frequency of spike discharges evoked by the depolarizing current pulses and produced a small increase in the rate of background firing activity. The baseline resting potential and input resistance were essentially unchanged by apamin. Apamin also diminished a late, slowly decaying component of inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) elicited by stimulation of the ventrolateral thalamus or the pyramidal tract. The apamin-induced changes were concomitant with a decrease of the decay time constant of both IPSPs and IPSCs and a positive shift in their reversal potential. The results suggest that the late, slowly decaying component of these inhibitory postsynaptic responses is generated by an apamin-sensitive Ca 2+-dependent K + conductance which is also responsible for the slow AHP.

[Pyloroplasty and motile functions of the stomach and duodenum].

Mongrel dogs were prepared by attaching 2 and 1 silver needle bipolar electrodes on the gastric antrum and bulbus of the duodenum, respectively. Among the obtained active potential from these dogs at chronic stage, investigations were performed mainly on the discharge frequency of spikes, propagation pattern of electrical excitation, and relationship of the stomach and duodenum. In addition, barium was loaded as the stomach contents and extraction dynamics of the loads were observed radiologically. The following was these investigations concerning about the pyloroplasty and motile functions of the stomach and duodenum. Experimental methods 1) Electromyography and extraction dynamics of stomach contents were observed in no treated control dogs. 2) Heineke-Mikulicz type pyloroplasty, Finney type pyloroplasty, or pylorectomy was performed on the above described control dogs. Electromyographical comparison was made among the types of pyloroplasty. 3) Dogs subjected to selective vagolysis (SV), selective proximal vagotomy (SPV), or gastric transection (Tr) were divided into groups with and without pyloroplasty. Electromyography and extraction dynamics of stomach contents were observed in these groups of animals. Results 1) In the control dogs, the mean discharge frequency of spikes in the gastric antrum at fasting time was 4.86 cycle/minute. The spikes propagated to the pyloric side periodically. The discharge frequency of spikes was reduced by the load of stomach contents which took about 120 minutes to be extracted. 2) When the types of pyloroplasty were compared, smaller electromyographical changes were obtained in dogs subjected to Heineke-Mikulicz type pyloroplasty. 3) Pyloroplasty did not affect the discharge frequency of spikes at fasting time, whereas, high incidences of antiperistaltic propagation pattern of electrdcal excitation were observed in dogs subjected to SPV. 4) When stomach contents were loaded, drainage effects of pyloroplasty were suggested from the discharge frequency of spikes, propagation pattern of electrical excitation, and findings in extraction dynamics of the stomach contents. In the dogs subjected to SPV, pylorplasty induced no significant fluctuations in the discharge frequency of spikes. Dogs subjected to Tr showed no improvement in the frequent antiperistaltic propagation pattern of electrical excitement after the pyloroplasty. 5) By pyloroplasty, the frequency of simultaneous generation of spikes in the gastric antrum and duodenum was decreased in the SV and Tr groups, while it was increased in the SPV group.

Neuropharmacological modulation of swimming activity and life span in a digenean parasite, Cercaria caribbea LXXI cable

1. 1. Exogenously applied neuropharmacological agents profoundly affected the swimming behaviour and survivorship of Cercaria caribbea LXXI. 2. 2. Propranolol (1.1–40 μM), haloperidol (0.66–0.133 mM) and physostigmine (0.08–2.5 mM) were the most potent reducers of population half-life (T 50). 3. 3. Some drugs (e.g. reserpine) produced apparent osmotic disturbances leading to shortened life span. 4. 4. Serotonin had the greatest excitatory effect on swimming and on the electrical activity, increasing the amplitude and frequency of spike discharge. Physostigmine most effectively reduced both parameters. 5. 5. Neuromuscular control of swimming may involve central excitatory nicotinic (cholinergic) and beta adrenergic influences, inhibitory muscarinic (cholinergic) and dopaminergic influences; and local excitatory muscarinic and serotonergic influences.

Chemoresponsiveness of intracerebellar nuclei neurones to l-aspartate, l-glutamate and related derivatives in rat cerebellar slices maintained in vitro

The sensitivity of intracerebellar nuclei neurones to pulse applications of l-aspartate. l-glutamate, N-methyl- d,l-aspartate and quisqualate was tested in rat cerebellar slices mainlained in vitro. The responses ol the nuclear neurones to the four agonists consisted of a transient and dose-dependent increase in their firing of simple spikes. When suprathreshold currents were used, quisqualate induced the highest increase in the spike discharge frequency of the cells. Quisqualate mediated responses were unaffected by steady applications of 2-amino-5-phosphonovalerate. whereas the sensitivity of the responses induced by the three other agonists was in the order N-methyl- d,l-aspartate. l-aspartate. l-glutamate. When the supervising solution was devoid of Mg 2+ ions. N-methyl- d,l-maspartate and l-aspartate mediated responses were much potentiated, while quisqualate induced responses were not enhanced. In such a medium, l-glutamate elicited responses were more or less potentiated depending on cells. These results suggest that rat intraeerebellar nuclei neurones hear both N-methyl- d-aspartate and non- N-methyl- d-maspartate. probably quisqualate. receptors, and that laspartate and l-glutamate have a mixed action upon both types. l-Aspartate preferentially activates N-methyl- d-aspartate receptors, whereas l-glutamate predominantly acts via non- N-methyl- d-aspartate receptors, Furihermore, the potency of l-glutamate in activating N-methyl- d-aspartate receptors appears to vary as a function of the cells.

Thermosensitive and osmoreceptive afferent fibers in the hepatic branch of the vagus nerve

The hepatic vagus nerve contains various thermosensitive afferent fibers which are widely varied in their sensitivity. Their Q 10 values lie between 4 and 16. The discharge rate is positively correlated with increase of liver temperature (warm fiber type). The result supports the existence of a thermosensitive structure in the liver which may possibly contribute to maintain thermal homeostasis. Neural responses to the osmotic changes in the perfusion solution have been analyzed. It was found that two different types of osmosensitive afferent fibers exist in the hepatic vagus; one is characterized by increasing the frequency of spike discharges in response to higher osmotic pressure, while the other shows the same response to lowered levels. Behavioral changes caused by hepatic vagotomy were observed. These results provide evidence for the existence of an osmoreceptor mechanism. The role of these hepatic afferent nerves in homeostasis are briefly discussed.

Adrenergic and Cholinergic Activity of the Japanese Quail Oviduct In Vitro

The responses to isoprenaline, phenylephrine, and carbachol in different segments of isolated intact oviduct were studied. Smooth muscle electrical activity was recorded with suction electrodes placed, one electrode in each, in the infundibulum, proximal magnum, distal magnum, isthmus, shell gland, and vagina. The drugs were added cumulatively. Only in the magnum did isoprenaline cause a significant change in the frequency of spike discharges; the decrease was about 20%. The effects of phenylephrine were not so clear, although the frequency of the electrical activity increased 30% in the shell gland. With the exception of the infundibulum, carbachol significantly increased the frequency of the oviductal electrical activity.It was concluded that adrenergic nerves have only a minor role in controlling quail oviductal smooth muscle because the oviduct was rather insensitive to adrenergic drugs whereas the cholinergic drug carbachol caused a strong response.