Slow Oscillations Of Membrane Potential Research Articles

Involvement of Na+/K+pump in fine modulation of bursting activity of the snail Br neuron by 10 mT static magnetic field

The spontaneously active Br neuron from the brain-subesophageal ganglion complex of the garden snail Helix pomatia rhythmically generates regular bursts of action potentials with quiescent intervals accompanied by slow oscillations of membrane potential. We examined the involvement of the Na(+)/K(+) pump in modulating its bursting activity by applying a static magnetic field. Whole snail brains and Br neuron were exposed to the 10-mT static magnetic field for 15min. Biochemical data showed that Na(+)/K(+)-ATPase activity increased almost twofold after exposure of snail brains to the static magnetic field. Similarly, (31)P NMR data revealed a trend of increasing ATP consumption and increase in intracellular pH mediated by the Na(+)/H(+) exchanger in snail brains exposed to the static magnetic field. Importantly, current clamp recordings from the Br neuron confirmed the increase in activity of the Na(+)/K(+) pump after exposure to the static magnetic field, as the magnitude of ouabain's effect measured on the membrane resting potential, action potential, and interspike interval duration was higher in neurons exposed to the magnetic field. Metabolic pathways through which the magnetic field influenced the Na(+)/K(+) pump could involve phosphorylation and dephosphorylation, as blocking these processes abolished the effect of the static magnetic field.

Active Hippocampal Networks Undergo Spontaneous Synaptic Modification

The brain is self-writable; as the brain voluntarily adapts itself to a changing environment, the neural circuitry rearranges its functional connectivity by referring to its own activity. How the internal activity modifies synaptic weights is largely unknown, however. Here we report that spontaneous activity causes complex reorganization of synaptic connectivity without any external (or artificial) stimuli. Under physiologically relevant ionic conditions, CA3 pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable slow oscillations of membrane potential, alternating between the so-called UP and DOWN states. The generation of slow oscillations did not require fast synaptic transmission, but their patterns were coordinated by local circuit activity. In the course of generating spontaneous activity, individual neurons acquired bidirectional long-lasting synaptic modification. The spontaneous synaptic plasticity depended on a rise in intracellular calcium concentrations of postsynaptic cells, but not on NMDA receptor activity. The direction and amount of the plasticity varied depending on slow oscillation patterns and synapse locations, and thus, they were diverse in a network. Once this global synaptic refinement occurred, the same neurons now displayed different patterns of spontaneous activity, which in turn exhibited different levels of synaptic plasticity. Thus, active networks continuously update their internal states through ongoing synaptic plasticity. With computational simulations, we suggest that with this slow oscillation-induced plasticity, a recurrent network converges on a more specific state, compared to that with spike timing-dependent plasticity alone.

Sleepy Dialogues between Cortex and Hippocampus: Who Talks to Whom?

During NREM sleep, neocortical neurons undergo near-synchronous transitions, every second or so, between UP states, during which they are depolarized and fire actively, and DOWN states, during which they are hyperpolarized and completely silent. In this issue of Neuron, Isomura et al. report that slow oscillations of membrane potential occur near-synchronously not only in neocortex but also in entorhinal cortex and subiculum. Within the hippocampus proper, pyramidal neurons lack the bistability of UP and DOWN states, but their firing is strongly modulated by cortical activity during the UP state. Intriguingly, many hippocampal neurons fire during the cortical DOWN state. Thus, during sleep UP states, the cortex can talk to the hippocampus, but it is unclear whether the hippocampus talks back.

State-Dependent Sensory Gating in Olfactory Cortex

Sensory systems show behavioral state-dependent gating of information flow that largely depends on the thalamus. Here we examined whether the state-dependent gating occurs in the central olfactory pathway that lacks a thalamic relay. In urethane-anesthetized rats, neocortical EEG showed a periodical alternation between two states: a slow-wave state (SWS) characterized by large and slow waves and a fast-wave state (FWS) characterized by faster waves. Single-unit recordings from olfactory cortex neurons showed robust spike responses to adequate odorants during FWS, whereas they showed only weak responses during SWS. The state-dependent change in odorant-evoked responses was observed in a majority of olfactory cortex neurons, but in only a small percentage of olfactory bulb neurons. These findings demonstrate a powerful state-dependent gating of odor information in the olfactory cortex that works in synchrony with the gating of other sensory systems. They suggest a state-dependent switchover of signal processing modes in the olfactory cortex.

Activation of Ih is necessary for patterning of mGluR and mAChR induced network activity in the hippocampal CA3 region

Neuronal networks of the hippocampal CA3 region generate stereotyped patterns of electrical activity in response to activation of metabotropic glutamate receptors (mGluRs) or muscarinic acetylcholine receptors (mAChRs) that consist of intermittent episodes of prolonged oscillatory activity. In light of the slow kinetics of such network responses, we investigated the possible contribution of the hyperpolarisation-activated inward current ( I h) in the generation and maintenance of hippocampal oscillatory states. Hippocampal ‘mini-slice’ experiments in which the main subfields of the hippocampus were isolated by transection of the connecting afferents revealed that the CA3 region was the primary generator of both mGluR and mAChR-mediated network responses. Subsequent patch-clamp experiments confirmed the presence of a prominent hyperpolarisation-activated inward current in the principal cells of the CA3 region that was sensitive to caesium chloride and the selective I h blocker ZD-7288. Furthermore, in the presence of mAChR or mGluR agonists these cells exhibited a slow membrane potential oscillation that was independent of AMPA receptor-mediated synaptic transmission. Blockade of I h suppressed this oscillation as well as mGluR and mAChR-induced theta based intermittent network oscillatory behaviour. These data support the idea that the I h pacemaker current is important in the generation of patterned neuronal activities in the hippocampus.

Electrical coupling can prevent expression of adult-like properties in an embryonic neural circuit.

Electrical coupling is widespread in developing nervous systems and plays a major role in circuit formation and patterning of activity. In most reported cases, such coupling between rhythmogenic neurons tends to synchronize and enhance their oscillatory behavior, thereby producing monophasic rhythmic output. However, in many adult networks, such as those responsible for rhythmic motor behavior, oscillatory neurons are linked by synaptic inhibition to produce rhythmic output with multiple phases. The question then arises whether such networks are still able to generate multiphasic output in the early stage of development when electrical coupling is abundant. A suitable model for addressing this issue is the lobster stomatogastric nervous system (STNS). In the adult animal, the STNS consists of three discrete neural networks that are comprised of oscillatory neurons interconnected by reciprocal inhibition. These networks generate three distinct rhythmic motor patterns with large amplitude neuronal oscillations. By contrast, in the embryo the same neuronal population expresses a single multiphasic rhythm with small-amplitude oscillations. Recent findings have revealed that adult-like network properties are already present early in the embryonic system but are masked by an as yet unknown mechanism. Here we use computer simulation to test whether extensive electrical coupling may be involved in masking adult-like properties in the embryonic STNS. Our basic model consists of three different adult-like STNS networks that are built of relaxation oscillators interconnected by reciprocal synaptic inhibition. Individual model cells generate slow membrane potential oscillations without action potentials. The introduction of widespread electrical coupling between members of these networks dampens oscillation amplitudes and, at moderate coupling strengths, may coordinate neuronal activity into a single rhythm with different phases, which is strongly reminiscent of embryonic STNS output. With a further increase in coupling strength, the system reaches one of two final states depending on the relative contribution of inhibition and inherent oscillatory properties within the networks: either fully synchronized and dampened oscillations, or a complete collapse of activity. Our simulations indicate that, beginning from either of these two states, the emergence of distinct adult networks during maturation may arise from a developmental decrease in electrical coupling that unmasks preexisting adult-like network properties.

Membrane capacitance of cortical neurons and glia during sleep oscillations and spike-wave seizures.

Dual intracellular recordings in vivo were used to disclose relationships between cortical neurons and glia during spontaneous slow (<1 Hz) sleep oscillations and spike-wave (SW) seizures in cat. Glial cells displayed a slow membrane potential oscillation (<1 Hz), in close synchrony with cortical neurons. In glia, each cycle of this oscillation was made of a round depolarizing potential of 1.5-3 mV. The depolarizing slope corresponded to a steady depolarization and sustained synaptic activity in neurons (duration, 0.5-0.8 s). The repolarization of the glial membrane (duration, 0.5-0.8 s) coincided with neuronal hyperpolarization, associated with disfacilitation, and suppressed synaptic activity in cortical networks. SW seizures in glial cells displayed phasic events, synchronized with neuronal paroxysmal potentials, superimposed on a plateau of depolarization, that lasted for the duration of the seizure. Measurements of the neuronal membrane capacitance during slow oscillating patterns showed small fluctuations around the resting values in relation to the phases of the slow oscillation. In contrast, the glial capacitance displayed a small-amplitude oscillation of 1-2 Hz, independent of phasic sleep and seizure activity. Additionally, in both cell types, SW seizures were associated with a modulatory, slower oscillation ( approximately 0.2 Hz) and a persistent increase of capacitance, developing in parallel with the progression of the seizure. These capacitance variations were dependent on the severity of the seizure and the distance between the presumed seizure focus and the recording site. We suggest that the capacitance variations may reflect changes in the membrane surface area (swelling) and/or of the interglial communication via gap junctions, which may affect the synchronization and propagation of paroxysmal activities.

Synchronous Behavior of Two Coupled Biological Neurons

We report experimental studies of synchronization phenomena in a pair of biological neurons that interact through naturally occurring, electrical coupling. When these neurons generate irregular bursts of spikes, the natural coupling synchronizes slow oscillations of membrane potential, but not the fast spikes. By adding artificial electrical coupling we studied transitions between synchrony and asynchrony in both slow oscillations and fast spikes. We discuss the dynamics of bursting and synchronization in living neurons with distributed functional morphology.

Simulation of bursting activity in theHelix RPa1 neuron: Role of calcium ions

A model of bursting activity in the RPal neuron of the snailHelix pomatia has been developed. In this model, calcium conductances do not play a key role in generation of slow oscillations of membrane potential (MP). The possibility of simulating the maintenance of bursting in the presence of cadmium ions is shown. Inclusion in the model of the calcium-inactivated calcium conductance makes it possible to reproduce both adaptation of the neuron to constant polarizing current, which modifies bursting, and the development of slow inward current when MP is clamped at different phases at the slow wave. In our simulations, the characteristic properties of bursts (such as an increase in the frequency of action potentials and a decrease in spike undershoot at the beginning of a burst) are due to the cumulative inactivation of potassium current. The advantages of the presented mathematical model of bursting compared with other models are discussed.

Membrane potential oscillations and corticothalamic connectivity in rat associational thalamic neurons in vitro

Thalamic relay neurons were recorded from the dorsolateral and lateroposterior nuclei of the rat thalamus in a superfused explant preparation. The mean membrane potential of these cells was -67 +/- 7 mV, input resistance 114 +/- 31 M omega and spike amplitude 75 +/- 6 mV. Low-threshold slow membrane potential oscillations (1-4 Hz) were present in about 46% of the neurons. They occurred either spontaneously or following a membrane potential perturbation. In a subpopulation of cells, we also observed a high-threshold membrane oscillation when cells were depolarized above -45 mV. This oscillation consisted of bursts of low-amplitude spikes interrupted by rhythmic after-hyperpolarizations. Stimulation of the corticothalamic pathway elicited prolonged inhibitory postsynaptic potentials in associational thalamic neurons. In the presence of picrotoxin, corticothalamic input evoked prominent excitatory postsynaptic responses that showed marked short-term synaptic plasticity. Our results suggest that associational thalamic neurons maintained in vitro have a strong tendency to exhibit membrane oscillations. In addition, they receive a direct excitatory cortical input that remained functional in explant preparation.

Apamin-sensitive potassium channels mediate agonist-induced oscillations of membrane potential in pituitary gonadotrophs

In cultured rat pituitary gonadotrophs, gonadotropin-releasing hormone (GnRH) induces rapid hyperpolarization of the cell membrane and causes cessation of the spontaneous electrical activity present in non-stimulated cells. This initial response to GnRH is followed by slow oscillations of membrane potential ( V m) which often exhibit brief bursts of action potentials (AP) fired from the peak of the oscillations. The hyperpolarization waves are synchronous with GnRH-induced elevations of cytoplasmic Ca 2+ concentration ([Ca 2+] i), such that V m maxima alternate with the peak values of [Ca 2+] i. The V m oscillations result from repetitive activation of apamin-sensitive K + channels by cytoplasmic Ca 2+. Thus, GnRH activation of Ca 2+ mobilization can generate a bursting pattern of membrane potential through the activation of K + channels against a background of spontaneous electrical activity.

Various Temporal Patterns and Chaos in an Auto-Active Neuron.

The regular spontaneous firing Onchidium neuron shows various discharge patterns depending on the dc polarizing current: regular beating, regular bursting and irregular bursting dischrges. The one-dimensional map of interspike intervals in irregular discharges indicates that fluctuations in interval are not random but deterministic chaos. These auto-active discharges occur due to steady state negative slope conductance in the subthreshold membrane potential region, and complex discharges patterns result from the interaction between spikes and slow membrane potential oscillations due to slow channels. The modeled neuron of Hodgikin and Huxley type replicates the experimental data very well and suggests a route to chaos through a cascade of period-doubling bifurcations. We also discuss importance of discharge patterns for signal transduction in the nervous system.

Control of feeding movements in the pteropod mollusc, Clione limacina

(1) The buccal apparatus of the pteropod marine mollusc Clione limacina, isolated together with buccal ganglia, could perform rhythmic feeding movements. Movements of the radula and the hooks (which the Clione inserts into the body of its prey) as well as the electroneurogram of the radular nerve were recorded. Usually one could observe rhythmic radula movements alone, while the hooks were motionless. But sometimes the hooks also performed rhythmic movements which were more or less synchronous with those of the radula. The radula movement cycle consisted of the protraction and the retraction phases, which were occasionally followed by a quiescent phase. Corresponding to each radula movement was a burst of activity in the radular nerve, consisting of the protractor and the retractor components. (2) Isolated buccal ganglia were capable of feeding rhythm generation. Most of the buccal neurons exhibited rhythmic activity correlating with the activity in the radular nerve. According to the phase of activity in the feeding cycle, rhythmic neurons were divided into two groups - the protractor and the retractor ones. The neurons within each of the groups were electrically coupled with each other. The protractor and retractor neurons inhibited each other. (3) Protractor and retractor neurons were extracted from buccal ganglia by means of a microelectrode. Many isolated cells generated slow oscillations of membrane potential and bursts of spikes, the pattern of this activity being similar to that before isolation. (4) A model of the feeding rhythm generator is discussed. It consists of two (protractor and retractor) groups of neurons with mutual inhibitory connections, neurons of each group being endogenous bursters.

Paradox response of frog muscle membrane to changes in external potassium.

Applying conventional microelectrode technique the anomalous behaviour of membrane potential in response to changes in [K+]o was demonstrated in normal and cevadine-treated muscles bathed in Cl- -free medium. Partial repolarization of the cevadine-depolarized membrane and reappearance of the slow membrane potential oscillation (SMPO) were induced by elevating [K+]o from 2.5 mM to 10-20 mM. Both effects were reversed by return to 2.5 mM [K+]o. The K-induced repolarization was markedly reduced by 20 mM Cs+, but not by 0.1 mM ouabain, 1 mM 4-aminopyridine, or 1 mM diethyl-pyrocarbonate. The elevation of [K+]o failed to repolarize muscle fibers that had been depolarized only to a small extent. No K-induced repolarization has been observed in Cl- -containing fluid. In cevadine-free experiments the omission of potassium from the extracellular space in Cl- -free solution hyperpolarized some of the fibers, while depolarized others. Strong electrical stimuli applied in zero K-zero Cl solution turned all the fibers into depolarized state; on returning to 2.5 mM [K+]o complete repolarization was achieved in most of the fibers. It has been concluded that the paradox response of the muscle membrane to changes in [K+]o can be attributed to the K-dependent conductance changes of the inward rectifier K channel providing an explanation for the plateau-formation of SMPO and for the existence of two stable levels of membrane potential of the skeletal muscle bathed in Cl- -free medium.

AF1, a sequenced bioactive neuropeptide isolated from the nematode ascaris suum

An FMRFamide-like neuropeptide, named AF1, was isolated from head extracts of the nematode Ascaris suum using five steps of HPLC. AF1 is a heptapeptide with the amino acid sequence Lys-Asn-Glu-Phe-Ile-Arg-Phe-NH 2. Synthetic AF1 (10 −9 to 10 −7 M) rapidly and reversibly abolished slow membrane potential oscillations of identified ventral and dorsal inhibitory motoneurons and selectively reduced their input resistances. Synaptic transmission was not blocked. In intact Ascaris, AF1 inhibited locomotory movements. This study indicates a potential physiological role for an endogenous neuropeptide in nematodes.

Slow oscillations of membrane potential in interneurons that control heartbeat in the medicinal leech

In the preceding paper (Arbas and Calabrese, 1987), we identified several properties that contribute to the activity of neurons (HN cells) that control heartbeat in the medicinal leech. Premotor HN (7) interneurons, which do not generate the heartbeat rhythm, exhibit Na+-dependent fast action potentials, Ca2+-mediated plateau potentials in the absence of Na+, and hyperpolarization-activated "restorative" changes in membrane potential that depolarize the membrane potential on hyperpolarization due to injected currents or synaptic inhibition. HN interneurons of ganglia 3 and 4 (i.e., timing oscillator interneurons) exhibit all of the properties described for HN (7) interneurons and have the additional characteristic that they are connected in oscillatory circuits. Reciprocal oscillations in membrane potential occurred in the bilateral HN interneurons (3) and (4) in the presence of elevated Ca2+ that were independent of Na+ -mediated action potentials. Their ability to oscillate in this way is based on 3 parameters: (1) production of a regenerative plateau potential by one of the pair of HN neurons in either ganglion, (2) inhibition of the contralateral HN neuron by the HN neuron in plateau, and (3) a phase transition mediated by escape from inhibition by the hyperpolarized HN neuron. The conductances responsible for restorative membrane potential shifts activated by hyperpolarization during synaptic inhibition may mediate the escape from inhibition that times the phase transition of the 2 HN neurons.

Central generation of swimming activity in the hydrozoan jellyfish Aequorea aequorea.

Swimming in Aequorea is controlled by a network of electrically coupled neurons (swim motorneurons) located in the inner nerve ring. The network is made up of the largest neurons in the ring, up to 22 microns in diameter. Intracellular recordings from swim motorneurons reveal slow membrane potential oscillations and a superimposed barrage of synaptic "noise." The synaptic noise, but not the slow oscillations, is eliminated in seawater containing an elevated Mg++ concentration. The swim motorneurons produce a rapid burst of two to eight action potentials preceding each contraction of the subumbrella. Spontaneous bursting persists in high-Mg++ seawater. Injected ramp currents indicated a "bursty" character of the swim motorneurons as suprathreshold depolarizations produced repetitive bursting with an increasing burst frequency with increased depolarization. Hyperpolarizing currents locally blocked spiking in swim motorneurons. Intercellular coupling was demonstrated with Lucifer Yellow injection and dual electrode recordings. In dye fills, only the large neurons of the inner nerve ring were dye-coupled. Two pieces of evidence suggest that swim motorneurons activate the overlying epithelial cells via chemical synapses. First, direct synaptic connections have been noted in ultrastructural examination of the inner nerve ring region. Second, dual recordings from a swim motorneuron and an epithelial cell reveal a 1:1 correspondence between neuron spikes and epithelial synaptic potentials. The synaptic potentials occur with a latency as short as 3 ms which is constant in any one recording session. The results suggest that the swim motorneuron network of Aequorea not only performs a motorneuron function, but also serves as the pattern generator for swimming activity.

Rhythmic membrane potential changes in hamster parasympathetic neurons

Two types of rhythmic membrane potentials in hamster submandibular neurons: (i) slow oscillations of membrane potential (SOMP); and (ii) spontaneous or caffeine-induced rhythmic hyperpolarizing potentials (C-HPs), have been analyzed. SOMPs occurred spontaneously, roughly in sinusoidal forms, between the subthreshold range and the potassium equilibrium potential (E K, approximately -85 mV). The average amplitude of SOMPs from crest to trough was 12 mV with an average crest to crest interval of 6 min. The largest amplitude of SOMPs was seen when their median membrane potentials were between -65 and -70 mV; values outside this range attenuated the amplitude of SOMPs. SOMPs were hardly discernible at or near E K. The membrane resistance was, in general, higher at the crest than at the trough. In eserine-treated preparations, SOMPs of varying durations following postsynaptic potentials were triggered by preganglionic repetitive stimulation. Reduction of extracellular K + concentration increased the amplitude of SOMP without changing its frequency. This effect was noted at times before K +-free induced membrane depolarization occurred. The amplitude of the SOMP decreased in Ca 2+-free saline with concomitant depolarization; conversely, in saline in which the Ca 2+ concentration was doubled the membrane potential (E m) was found to be again stable near the E K level. A transient hyperpolarization occurred following intracellular Ca 2+ injection when the E m of the preinjected state was between -45 and -60 mV. Among K +-conductance (G K) blockers (TEA, 3- and 4-aminopyridine, Cs + and Ba 2+ examined, only Ba 2+ at 5 mM reduced both amplitude and frequency of C-HPs significantly. All Ca 2+-conductance (G Ca) blockers (Co 2+ and Mn 2+ at 5 mM, Cd 2+ and La 3+ at 1 mM, and D-600 at 0.4 mg/ml) prevented synaptic transmission and abolished spike-induced late hyperpolarizing afterpotential. C-HPs were nearly abolished by these agents in 4 mM Ca 2+-containing saline. Mitochondrial inhibitors (DNP, CCCP, KCN, NaN 3) in a concentration range between 10 −4M and 10 −5 M, hyperpolarized the membran before depolarizing and abolishing C-HPs. However, the plasma membrane Na +-pump inhibitor ouabain, at concentrations up to 5 × 10 −4 M, did not affect C-HPs during 1 h perfusion in the majority of neurons; no membrane hyperpolarization was induced, although a gradual depolarization did occur. Both ruthenium red (5 mM) and quinine (5 × 10 −4 M) abolished C-HPs. It is assumed that the two above types of membrane potential changes are generated by the Ca 2+-activated G K increase, which, in turn, is under the control of mitochondrial Ca 2+ regulatory activity.

A model of oscillation generation by molluscan neurons

A model describing slow oscillations of membrane potential in molluscan neurons is suggested. It is based on the view that the depolarization phase is due to the slow calcium current, whereas the hyperpolarization phase is due to the potassium current activated by intracellular Ca ions. It is shown that depending on values of the parameters of the model there are three possible types of electrical activity of the neurons: stable membrane hyperpolarization up to the resting potential which is between −49 and −53 mV; slow oscillations of membrane potential from −30 to −60 mV, with a period of 12–17 sec, and stable membrane depolarization to between −40 and −30 mV, which may lead to the onset of stable rhythmic activity of these neurons. Dependence of the amplitude of the oscillations of potential on the extracellular concentration of Ca, K, and Na ions was calculated and agrees qualitatively with the experimental data of Barker and Gainer [4].

Effects of neurotropic substances—apomorphine, piribedil, bromocriptine and metergoline—on the excitability of identifiable molluscan giant neurons sensitive to dopamine and 5-hydroxytryptamine

1. It was examined whether four neurotropic substances—apomorphine, piribedil, bromocriptine and metergoline—have either an agonistic or antagonistic effect to dopamine (DA) and 5-hydroxytryptamine (5-HT), by using the two giant neurons (PON, periodically oscillating neuron and TAN, tonically autoactive neuron), which are sensitive to the two putative neurotransmitters and identified in the suboesophageal ganglia of an African giant snail ( Achatina fulica Férussac). 2. The four neurotropic substances examined at 10 −4 kg/1 had neither an agonistic nor antagonistic effect to both 5-HT and DA on the two giant neurons. 3. Both apomorphine and metergoline at 10 −4 kg/1 sometimes produced abnormal spike discharges of TAN, such as the doublet spikes or the slow oscillations of membrane potential. 4. Bromocriptine at 10 −4 kg/1 occasionally caused a transient hyperpolarization of the TAN membrane potential, which was probably due to the synaptic influences.