scholarly journals Sodium Along With Low-Threshold Potassium Currents Enhance Coincidence Detection of Subthreshold Noisy Signals in MSO Neurons

2004 ◽  
Vol 91 (6) ◽  
pp. 2465-2473 ◽  
Author(s):  
Gytis Svirskis ◽  
Vibhakar Kotak ◽  
Dan H. Sanes ◽  
John Rinzel
Keyword(s):  
Sodium Current ◽  
Sodium Concentration ◽  
Coincidence Detection ◽  
Reverse Correlation ◽  
Spike Generation ◽  
Voltage Dependent ◽  
Two Factors ◽  
Noisy Signals ◽  
Low Threshold

Voltage-dependent membrane conductances support specific neurophysiological properties. To investigate the mechanisms of coincidence detection, we activated gerbil medial superior olivary (MSO) neurons with dynamic current-clamp stimuli in vitro. Spike-triggered reverse-correlation analysis for injected current was used to evaluate the integration of subthreshold noisy signals. Consistent with previous reports, the partial blockade of low-threshold potassium channels ( IKLT) reduced coincidence detection by slowing the rise of current needed on average to evoke a spike. However, two factors point toward the involvement of a second mechanism. First, the reverse correlation currents revealed that spike generation was associated with a preceding hyperpolarization. Second, rebound action potentials are 45% larger compared to depolarization-evoked spikes in the presence of an IKLT antagonist. These observations suggest that the sodium current ( INa) was substantially inactivated at rest. To test this idea, INa was enhanced by increasing extracellular sodium concentration. This manipulation reduced coincidence detection, as reflected by slower spike-triggering current, and diminished the hyperpolarization phase in the reverse-correlation currents. As expected, a small outward bias current decreased the pre-spike hyperpolarization phase, and TTX blockade of INa nearly eliminated the hyperpolarization phase in the reverse correlation current. A computer model including Hodgkin-Huxley type conductances for spike generation and for IKLT showed reduction in coincidence detection when IKLT was reduced or when INa was increased. We hypothesize that desirable synaptic signals first remove some inactivation of INa and reduce activation of IKLT to create a brief temporal window for coincidence detection of subthreshold noisy signals.

The development of voltege-dependent ionic conductances In murine spinal cord neurones in culture

1988 ◽  
Vol 66 (10) ◽  
pp. 1328-1336 ◽  
Author(s):  
C. Krieger ◽  
T. A. Sears
Keyword(s):  
Spinal Cord ◽  
Sodium Current ◽  
Potassium Conductance ◽  
Calcium Currents ◽  
Delayed Rectifier ◽  
Patch Clamp Technique ◽  
Calcium Dependent ◽  
Ionic Conductances ◽  
Voltage Dependent

The development of voltage-dependent ionic conductances of foetal mouse spinal cord neurones was examined using the whole-cell patch-clamp technique on neurones cultured from embryos aged 10–12 days (E10–E12) which were studied between the first day in vitro (V1) to V10. A delayed rectifier potassium conductance (IK) and a leak conductance were observed in neurones of E10.V1, E11, V1, and E12, V1 as well as in neurones cultured for longer periods. A rapidly activating and inactivating potassium conductance (IA) was seen in neurones from E11, V2 and E12, V1 and at longer times in vitro. A tetrodotoxin (TTX) sensitive sodium-dependent inward current was observed in neurones of E11 and E12 from V1 onwards. Calcium-dependent conductances were not detectable in these neurones unless the external calcium concentration was raised 10- to 20-foid and potassium conductances were blocked. Under these conditions calcium currents could be observed as early as E11, V3 and E12, V2 and at subsequent times in vitro. The pattern of development of voltage-dependent ionic conductances in murine spinal neurones is such that initially leak and potassium currents are present followed by sodium current and subsequently calcium current.

scholarly journals Monoterpenoid Terpinen-4-ol Exhibits Anticonvulsant Activity in Behavioural and Electrophysiological Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Franklin F. F. Nóbrega ◽  
Mirian G. S. S. Salvadori ◽  
Cintia J. Masson ◽  
Carlos F. Mello ◽  
Tiago S. Nascimento ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Sodium Current ◽  
Anticonvulsant Effect ◽  
Aromatic Plants ◽  
Gabaergic Neurotransmission ◽  
Benzodiazepine Binding ◽  
Voltage Dependent ◽  
Electrophysiological Studies ◽  
Anticonvulsant Effects

Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of theGABAAreceptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.

Cellular Mechanisms Underlying Activity Patterns in the Monkey Thalamus During Visual Behavior

2000 ◽  
Vol 84 (4) ◽  
pp. 1982-1987 ◽  
Author(s):  
E. J. Ramcharan ◽  
C. L. Cox ◽  
X. J. Zhan ◽  
S. M. Sherman ◽  
J. W. Gnadt
Keyword(s):  
Visual Processing ◽  
Activity Patterns ◽  
Burst Firing ◽  
Cellular Mechanisms ◽  
Cellular Processes ◽  
Thalamic Relay ◽  
Voltage Dependent ◽  
Low Threshold ◽  
Behaving Monkeys

We show for the first time with in vitro recording that burst firing in thalamic relay cells of the monkey is evoked by activation of voltage-dependent, low threshold Ca2+ spikes (LTSs), as has been described in other mammals. Due to variations in LTS amplitude, the number of action potentials evoked by an LTS could vary between 1 and 8. These data confirm the presence of two modes of firing in the monkey for thalamic relay cells, tonic and burst, the latter related to the activation of LTSs. With these details of the cellular processes underlying burst firing, we could account for many of the firing patterns we recorded from the lateral geniculate nucleus of the thalamus in behaving monkeys. In particular, we found clear evidence of burst firing during alert wakefulness, which had been thought to occur only during sleep or certain pathological states. This makes it likely that the burst firing seen in awake humans has the same cellular basis of LTSs, and this supports previous suggestions that burst firing represents an important relay mode for visual processing.

Correlation of physiologically and morphologically identified neuronal types in human association cortex in vitro

1991 ◽  
Vol 66 (6) ◽  
pp. 1825-1837 ◽  
Author(s):  
R. C. Foehring ◽  
N. M. Lorenzon ◽  
P. Herron ◽  
C. J. Wilson
Keyword(s):  
Spiking Neurons ◽  
Burst Firing ◽  
Repetitive Firing ◽  
Association Cortex ◽  
Firing Behavior ◽  
Voltage Dependent ◽  
Low Threshold ◽  
Fast Spiking ◽  
Human Association

1. We examined whether the three physiologically defined neuron types described for rodent neocortex were also evident in human association cortex studied in an in vitro brain slice preparation. We also examined the relationship between physiological and morphological cell type in human neocortical neurons. In particular, we tested whether burst-firing neurons were numerous in regions of human cortex that are susceptible to seizures. 2. Although we sampled regular-spiking and fast-spiking neurons, we observed no true burst-firing neurons, as defined for rodent cortex. We did find neurons that displayed a voltage-dependent shift in firing behavior. Because this behavior was due, in large part, to a low-threshold calcium conductance, we called these cells low-threshold spike (LTS) neurons. 3. Regular-spiking neurons and LTS neurons only differed in the voltage dependence of firing behavior and the first few interspike intervals (ISIs) of repetitive firing in response to small current injections (from hyperpolarized membrane potentials). Because of the general similarities between the two types, we consider the LTS cells to be a subgroup of regular-spiking cells. 4. All biocytin-filled regular-spiking neurons were spiny and pyramidal and found in layers II-VI. The lone filled fast-spiking cell was aspiny and nonpyramidal (layer V). The LTS neurons were morphologically heterogeneous. We found 80% of LTS neurons to be spiny and pyramidal, but 20% were aspiny nonpyramidal cells. LTS neurons were located in layers II-VI. 5. In conclusion, human association cortex contains two of three physiological cell types described in rodent cortex: regular spiking and fast spiking. These physiological types corresponded to spiny, pyramidal, and aspiny, nonpyramidal cells, respectively. We sampled no intrinsic burst-firing neurons in human association cortex. LTS neurons exhibited voltage-dependent changes in firing behavior and were morphologically heterogeneous: most LTS cells were spiny and pyramidal, but two cells were found to be aspiny and nonpyramidal. It is not clear whether the absence of burst-firing neurons or the morphological heterogeneity of LTS neurons are due to species differences or differences in cortical areas.

Role of [Na+]i and [Ca2+]i in nicotine-induced norepinephrine release from bovine adrenal chromaffin cells

1995 ◽  
Vol 269 (3) ◽  
pp. C572-C581 ◽  
Author(s):  
S. H. Gerber ◽  
A. Haunstetter ◽  
C. Kruger ◽  
A. Kaufmann ◽  
R. Nobiling ◽  
...  
Keyword(s):  
Nicotinic Receptor ◽  
Chromaffin Cells ◽  
Sodium Concentration ◽  
Release Mechanism ◽  
Adrenal Chromaffin Cells ◽  
Sodium Influx ◽  
Voltage Dependent ◽  
Adrenal Chromaffin

Intracellular free sodium ([Na+]i) and calcium ([Ca2+]i) concentrations were determined by sodium-binding benzofuran isophthalate (SBFI) and fura 2 microfluorimetry, respectively, in bovine adrenal chromaffin cells (BCC). Validation of SBFI microfluorimetry by in vitro and in vivo calibration revealed a reliable assessment of [Na+]i within a range of 1-30 mM in single BCC. Nicotine (0.1-10 microM) induced concentration-dependent increases of both [Na+]i (from 3.3 +/- 0.1 to 25.6 +/- 0.4 mM, n = 76, P < 0.001) and [Ca2+]i (from 64 +/- 1 to 467 +/- 16 nM, n = 87, P < 0.001), which were accompanied by an increase in [3H]norepinephrine (NE) release. Consistent with an exocytotic release mechanism, nicotine-induced increments of [Ca2+]i and [3H]NE release were reduced under calcium-free conditions and by gadolinium chloride (40 microM), whereas [Na+]i was not affected. In contrast, a parallel attenuation of nicotine-evoked changes in [Na+]i, [Ca2+]i, and [3H]NE release was observed during reduction of the extracellular sodium concentration. The nicotine-evoked responses were neutralized by the nicotinic receptor antagonist hexamethonium (100 microM) but not by blockade of voltage-dependent sodium channels (1 microM tetrodotoxin). In conclusion, the nicotine-induced exocytotic release of [3H]NE is triggered by an increase in [Ca2+]i, which is facilitated by sodium influx through the nicotinic receptor ionophore.

Integrator or Coincidence Detector: A Novel Measure Based on the Discrete Reverse Correlation to Determine a Neuron’s Operational Mode

2016 ◽  
Vol 28 (10) ◽  
pp. 2091-2128 ◽  
Author(s):  
Jacob Kanev ◽  
Achilleas Koutsou ◽  
Chris Christodoulou ◽  
Klaus Obermayer
Keyword(s):  
Background Noise ◽  
Coincidence Detection ◽  
Reverse Correlation ◽  
Gap Detection ◽  
Operational Mode ◽  
Spike Generation ◽  
Neural Drive ◽  
Definition Of ◽  
Operational Modes ◽  
Complex Manner

In this letter, we propose a definition of the operational mode of a neuron, that is, whether a neuron integrates over its input or detects coincidences. We complete the range of possible operational modes by a new mode we call gap detection, which means that a neuron responds to gaps in its stimulus. We propose a measure consisting of two scalar values, both ranging from −1 to +1: the neural drive, which indicates whether its stimulus excites the neuron, serves as background noise, or inhibits it; the neural mode, which indicates whether the neuron’s response is the result of integration over its input, of coincidence detection, or of gap detection; with all three modes possible for all neural drive values. This is a pure spike-based measure and can be applied to measure the influence of either all or subset of a neuron’s stimulus. We derive the measure by decomposing the reverse correlation, test it in several artificial and biological settings, and compare it to other measures, finding little or no correlation between them. We relate the results of the measure to neural parameters and investigate the effect of time delay during spike generation. Our results suggest that a neuron can use several different modes simultaneously on different subsets of its stimulus to enable it to respond to its stimulus in a complex manner.

Induction of voltage-dependent sodium channels by in vitro differentiation of human retinoblastoma cells

1993 ◽  
Vol 70 (4) ◽  
pp. 1487-1496 ◽  
Author(s):  
M. del Pilar Gomez ◽  
G. Waloga ◽  
E. Nasi
Keyword(s):  
Sodium Current ◽  
Inactivation Kinetics ◽  
Bathing Solution ◽  
Inactivation Curve ◽  
Inward Current ◽  
Differentiated Cells ◽  
Sodium Removal ◽  
Voltage Dependent ◽  
Undifferentiated Cells

1. Neuronlike differentiation of Y-79 retinoblastoma was chemically induced in vitro, by plating the cells onto a poly-D-lysine and laminin substrate. The changes in voltage-dependent conductances after 48-72 h were examined with the whole-cell tight-seal and the perforated-patch recording techniques. 2. Although outward currents carried by potassium ions appeared qualitatively similar before and after differentiation, the depolarization-activated transient inward current displayed a pronounced acceleration of its activation and inactivation kinetics. 3. After differentiation, both the threshold of activation and the steady-state inactivation curve of the inward current are displaced in the negative direction by approximately 10-20 mV as compared with untreated cells. The current attains its peak amplitude in approximately 1 ms at maximum activating voltages, and decays within 3 ms. In contrast, in undifferentiated cells these values are on the order of 6 and 60 ms, respectively. The time to recover from inactivation is also shortened 20-fold in differentiated cells. 4. Unlike the mixed conductance of undifferentiated cells, which requires extracellular calcium, the inward current of the neuronlike differentiated cells is insensitive to manipulations of external calcium. Instead, it can be completely abolished in a reversible way by sodium removal or by micromolar concentrations of tetrodotoxin (TTX) in the bathing solution. As such, it resembles in all salient respects the voltage-dependent sodium conductance of nerve cells. 5. The fast sodium current expressed after neuronal differentiation is not the result of a progressive enhancement of an existing conductance, because no such component is discernible in undifferentiated cells. Moreover, recordings performed in cells at early stages of differentiation also failed to reveal the coexistence of the immature and the differentiated inward currents. 6. A possible account of the present observations is that the native inward current of undifferentiated Y-79 cells may correspond to a precursor form of the mature channel, and the observed developmental changes induced by chemical differentiation could be a consequence of progressive modification of the original channels, rather than expression of a separate class of proteins.

Electrophysiology of the mammillary complex in vitro. II. Medial mammillary neurons

1992 ◽  
Vol 68 (4) ◽  
pp. 1321-1331 ◽  
Author(s):  
A. Alonso ◽  
R. R. Llinas
Keyword(s):  
Low Frequency ◽  
Input Resistance ◽  
Resting Potential ◽  
High Threshold ◽  
Potential Oscillations ◽  
Electrophysiological Properties ◽  
Voltage Dependent ◽  
Low Threshold ◽  
Membrane Potential Oscillations

1. The electrophysiological properties of guinea pig medial mammillary body (MMB) neurons were studied using an in vitro slice preparation. 2. The neurons (n = 80) had an average resting potential of -57 +/- 5.5 (SD) mV, an input resistance of 176 +/- 83 M omega, and a spike amplitude of 58 +/- 15.7 mV. Most of the neurons were silent at rest (n = 52), but some fired spontaneous single spikes (n = 16) or spike bursts (n = 14). 3. The main electrophysiological characteristic of MMB neurons was the ability to generate Ca(2+)-dependent regenerative events, which resulted in very robust burst responses. However, this regenerative event was not the same for all neurons, ranging from typical low-threshold Ca2+ spikes (LTSs) to intermediate-threshold plateau potentials (ITPs). 4. The ITPs were distinct from the LTSs in that they lasted > or = 100 ms and were not inactivated at membrane potentials at or positive to -55 mV. 5. Some cells with a prominent ITP and no LTS (n = 36) displayed repetitive, usually rhythmic, bursting (n = 14). This ITP could be powerful enough to maintain rhythmic membrane potential oscillations after pharmacological block of Na+ conductances. 6. A group of 32 MMB neurons displayed complex bursting that was generated by activation of both LTSs and ITPs. This was established on the basis of their distinct time- and voltage-dependent characteristics. In a group of neurons (n = 14), the burst responses were exclusively generated by an LTS; however, a Ca(2+)-dependent plateau potential contributed to the generation of rebound-triggered oscillatory firing. 7. In addition to the Ca(2+)-dependent LTS and/or ITP, MMB neurons always displayed high-threshold Ca2+ spikes after reduction of K+ conductances with tetraethylammonium. 8. MMB neurons display one of the richer varieties of voltage-dependent Ca2+ conductances so far encountered in mammalian CNS. We propose that the very prominent endogenous bursting and oscillatory properties of MB neurons allow this nuclear complex to function as an oscillatory relay for the transmission of low-frequency rhythmic activities throughout the limbic circuit.

Hyperpolarization-activated currents, IH and IKIR, in rat dorsal motor nucleus of the vagus neurons in vitro

1994 ◽  
Vol 71 (4) ◽  
pp. 1308-1317 ◽  
Author(s):  
R. A. Travagli ◽  
R. A. Gillis
Keyword(s):  
Firing Rate ◽  
Sodium Concentration ◽  
Peak Amplitude ◽  
Resting Potential ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Voltage Dependent ◽  
Ion Substitution ◽  
Hyperpolarization Activated Current

1. The patch-clamp technique applied to the in vitro thin brain slice preparation was used to record voltage and current traces from visually identified neurons of the rat dorsal motor nucleus of the vagus (DMV). 2. The majority of DMV neurons (102 of 159, i.e., 64%) showed a slowly developing hyperpolarization-activated current that had its threshold generally positive to resting potential and that exhibited a half-maximal activation at -90 mV and full saturation at -127 mV. The activation time constant was strongly voltage dependent, decreasing with hyperpolarization. 3. Ion substitution experiments identified the hyperpolarization-activated current as IH. In fact, the current was potassium- and sodium-sensitive. Raising the extracellular potassium concentration from 3.75 to 20 mM increased the current peak amplitude in a voltage-dependent manner, whereas lowering extracellular sodium concentration from 146 to 26 mM decreased the current peak amplitude with a shift of the activation threshold toward more hyperpolarized potentials. The IH was significantly reduced during perfusion with either external cesium or rubidium but was insensitive to barium and tetraethylammonium (TEA). 4. A subset of DMV neurons (44 of 159, i.e., 28%) showed the presence of fast inward rectification but no IH. The current was activated at potentials close to the potassium equilibrium potential and reached steady state within 10 ms from the onset of the hyperpolarizing step. 5. Ion substitution experiments identified this hyperpolarization-activated current as IKIR. In fact, the current was potassium sensitive; its activation curve shifted toward less negative potentials with increasing potassium concentrations. IKIR was sodium insensitive, being unaffected by the lowering of the external sodium concentration. IKIR was significantly reduced during perfusion with cesium, barium, and TEA. 6. In the DMV neuronal subpopulation expressing IH, the IH contribution to the total cell conductance was approximately 30% at -87 to -97 mV. Furthermore, the same subpopulation of neurons was hyperpolarized in a voltage-related manner on perfusion with 5 mM cesium: at -57 mV, cesium induced a hyperpolarization of 5.6 +/- 1.3 (SE) mV, whereas at -72 mV the cesium-induced hyperpolarization was 26 +/- 4.4 mV. 7. Perfusion with 5 mM cesium reduced the spontaneous firing rate of a subset of neurons exhibiting IH but cesium never decreased the firing rate of neurons exhibiting IKIR.(ABSTRACT TRUNCATED AT 400 WORDS)

3 (2) Factorial Design Assisted Crushed Puffed Rice-HPMC-Chitosan based Hydrodynamically Balanced System of Metoprolol Succinate

2020 ◽  
Vol 10 (3) ◽  
pp. 237-249
Author(s):  
Shashank Soni ◽  
Veerma Ram ◽  
Anurag Verma
Keyword(s):  
Drug Release ◽  
Factorial Design ◽  
Hydroxypropyl Methylcellulose ◽  
Batch Size ◽  
Metoprolol Succinate ◽  
Zero Order Kinetics ◽  
Two Factors ◽  
Puffed Rice ◽  
Model Drug

Introduction: Hydrodynamically balanced system (HBS) possesses prolonged and continuous delivery of the drug to the gastrointestinal tract which improves the rate and extent of medications that have a narrow absorption window. The objective of this work was to develop a Hydrodynamically Balanced System (HBS) of Metoprolol Succinate (MS) as a model drug for sustained stomach specific delivery. Materials and Methods: Experimental batches were designed according to 3(2) Taguchi factorial design. A total of 9 batches were prepared for batch size 100 capsules each. Formulations were prepared by physically blending MS with polymers followed by encapsulation into hard gelatin capsule shell of size 0. Polymers used were Low Molecular Weight Chitosan (LMWCH), Crushed Puffed Rice (CPR), and Hydroxypropyl Methylcellulose K15 M (HPMC K15M). Two factors used were buoyancy time (Y1) and time taken for 60% drug release (T60%; Y2). Results: The drug excipient interaction studies were performed by the thermal analysis method which depicts that no drug excipient interaction occurs. In vitro buoyancy studies and drug release studies revealed the efficacy of HBS to remain gastro retentive for a prolonged period and concurrently sustained the release of MS in highly acidic medium. All formulations followed zero-order kinetics. Conclusion: Developed HBS of MS with hydrogel-forming polymers could be an ideal delivery system for sustained stomach specific delivery and would be useful for the cardiac patients where the prolonged therapeutic action is required.

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