Biomedical subjects

F Amzica

Publications and source records attributed to F Amzica.

At least 19 recordsLinked to original sources

PubMed2003

Hyperpolarisation rectification in cat lateral geniculate neurons modulated by intact corticothalamic projections.

The intrinsic properties of thalamic neurons are influenced by synaptic activities in ascending pathways and corticofugal projections, as well as by the actions of neurotransmitters released by generalised modulatory systems. We focused on the effects of corticothalamic projections on the hyperpolarisation-activated cation current Ih. Intracellular recordings of thalamocortical neurons in the dorsal lateral geniculate (dLG) nucleus were performed in cats under ketamine-xylazine anaesthesia. At variance with the conventional way of recording intracellularly from thalamic neurons after partial or total ablation of the grey and white matter overlying the dLG, we preserved intact corticothalamic neuronal loops. Stimulating electrodes inserted into the optic tract and light-emitting-diodes as photic stimulation were used to identify the dLG neurons. The expression of the depolarising sag due to Ih depended on the state of cortical networks. Thalamic dLG Ih, induced by hyperpolarising current steps, was detected during the periods of cortical disfacilitation that occur during the cortical slow (< 1 Hz) oscillation, whereas Ih was absent during the active (depolarised) periods. The possibility that the excitatory corticothalamic projections could preclude the generation of the Ih was tested by applying a concentrated K+ solution (3 M) to the primary visual cortex. The same dLG neurons that did not display Ih before application of K+ were able to produce hyperpolarisation-activated depolarising sags during K+-induced cortical depression. Our data suggest that the thalamic clock-like delta oscillation, which results from an interplay between Ih and the low-threshold calcium current (IT), as described in preparations without cerebral cortex, is prevented in dLG neurons when corticothalamic loops are intact.

Action Potentials↗

PubMed2003

Sleep oscillations developing into seizures in corticothalamic systems.

PURPOSE: The aim of this article is to discuss the neuronal substrates of sleep oscillations leading to seizures consisting of spike-wave (SW) complexes at 2-4 Hz, mimicking those seen in absence epilepsy, or SW and polyspike-wave (PSW) complexes at 1.5-2.5 Hz, often associated with fast runs at 10-15 Hz, as in the Lennox-Gastaut syndrome. METHODS: Extracellular recordings were done in permanently implanted animals during the natural waking-sleep cycle. Single and dual simultaneous recordings from cortical neurons, cortical and thalamic neurons, or cortical neurons and glial cells were performed in cats under ketamine-xylazine anesthesia. RESULTS: (a) The minimal substrate of SW seizures is the neocortex because such seizures may occur in thalamectomized animals, in which spindles are absent. In intact-brain animals, SW seizures are initiated in neocortex and spread to the thalamus after a few seconds. The majority of thalamocortical (TC) neurons are steadily hyperpolarized throughout the cortical SW seizures. (b) In the Lennox-Gastaut syndrome, the paroxysmal depolarizing shifts (PDSs) associated with the EEG "spike" of SW/PSW complexes contain an important inhibitory component, whereas the hyperpolarization during the EEG "wave" component is not due to gamma-aminobutryic acid (GABA)ergic inhibitory postsynaptic potentials (IPSPs) but is ascribed to a mixture of disfacilitation and K+ currents. As is also the case with seizures consisting of pure SW complexes, the majority of TC neurons are hyperpolarized during the cortical paroxysms and disinhibited after the cessation of cortical seizures. CONCLUSIONS: Seizures with SW complexes and of the Lennox-Gastaut type preferentially evolve from sleep oscillations. They are initiated in neocortex and spread to the thalamus after a few seconds. The majority of TC neurons are inhibited during these seizures.

Animals↗

PubMed2001

Extracellular calcium fluctuations and intracellular potentials in the cortex during the slow sleep oscillation.

During slow wave sleep the main activity of cortical neurons consists of synchronous and rhythmic alternations of the membrane potential between depolarized and hyperpolarized values. The latter are long-lasting (200-600 ms) periods of silence. The mechanisms responsible for this periodical interruption of cortical network activity are unknown. Here we report a decrease of approximately 20% in the extracellular calcium concentration ([Ca](out)) progressively taking place in the cortex between the onset and the offset of the depolarizing phase of the slow sleep oscillation. Since [Ca](out) exerts a high gain modulation of synaptic transmission, we estimated the associated transmitter release probability and found a corresponding 50% drop. Thus the periods of silence occurring in the cortical network during slow wave sleep are promoted by recurrent [Ca](out) depletions.

Animals↗

PubMed2001

The brain decade in debate: VII. Neurobiology of sleep and dreams.

This article is a transcription of an electronic symposium held on February 5, 2001 by the Brazilian Society of Neuroscience and Behavior (SBNeC) during which eight specialists involved in clinical and experimental research on sleep and dreaming exposed their personal experience and theoretical points of view concerning these highly polemic subjects. Unlike most other bodily functions, sleep and dreaming cannot, so far, be defined in terms of definitive functions that play an ascribable role in maintaining the organism as a whole. Such difficulties appear quite clearly all along the discussions. In this symposium, concepts on sleep function range from a protective behavior to an essential function for maturation of the nervous system. Kleitman's hypothesis [Journal of Nervous and Mental Disease (1974), 159: 293-294] was discussed, according to which the basal state is not the wakeful state but sleep, from which we awake to eat, to protect ourselves, to procreate, etc. Dreams, on the other hand, were widely discussed, being considered either as an important step in consolidation of learning or simply the conscious identification of functional patterns derived from the configuration of released or revoked memorized information.

Animals↗

PubMed2000

Neuronal and glial membrane potentials during sleep and paroxysmal oscillations in the neocortex.

This study investigated the fluctuations in the membrane potential of cortical neurons and glial cells during the slow sleep oscillation and spike-wave (SW) seizures. We performed dual neuron-glia intracellular recordings together with multisite field potential recordings from cortical suprasylvian association areas 5 and 7 of cats under ketamine-xylazine anesthesia. Electrical stimuli applied to the cortex elicited responses consisting of a biphasic depolarization in glial cells, which was associated with an EPSP-IPSP sequence in neurons. During the slow (<1 Hz) oscillation, extracellular measurements of the potassium concentration revealed periodic increases with an amplitude of 1-2 mm, similar in shape to glial activities. We suggest that, through their uptake mechanisms, glia cells modulate the neuronal excitability and contribute to the pacing of the slow oscillation. The slow oscillation often evolved into SW paroxysms, mimicking sleep-triggered seizures. This transition was associated with increased coupling between the depolarizing events in neurons and glial cells. During seizures, the glial membrane potential displayed phasic negative events related to the onset of the paroxysmal depolarizing shifts in neurons. These events were not voltage dependent and increased their incidence and amplitude with the development of the seizure. It is suggested that the intraglial transient negativities represent field reflections of synchronized neuronal potentials. We propose that the mechanisms underlying the neuron-glia communication include, besides the traditional neurotransmitter- and ion-mediated pathways, field effects crossing their membranes as a function of the state of the cortical network.

Activity Cycles↗

PubMed2000

Changes in neuronal conductance during different components of cortically generated spike-wave seizures.

Neuronal conductance was studied in anesthetized cats during cortically generated spike-wave seizures arising from slow sleep oscillation. Single and dual intracellular recordings from neocortical neurons were used. The changes were similar whether the seizures occurred spontaneously, or were evoked by electrical stimulation or induced by bicuculline. In all seizures, the conductance increased from the very onset of the seizure and returned to control values only at the end of the postictal depression. Simultaneous intracellular recordings from two neurons showed that the neuron leading the other neuron displayed the largest increase in membrane conductance. The changes in neuronal conductance during the two phases of the slow sleep oscillation, i.e. highest during depolarizations and lowest during hyperpolarizations, were similar to those occurring during the "spike" and "wave" components of seizures. (1) Maximal conductance was found during the paroxysmal depolarizing shift corresponding to the electroencephalogram "spike" (median: 252 nS; range: 90 to more than 400 nS). It was highest at the onset of the depolarized plateau and decreased thereafter. (2) During the hyperpolarization corresponding to the electroencephalogram "wave", the conductance was significantly lower (median: 71 nS; range: 41 to 140 nS). (3) The conductance was elevated during the fast runs (median: 230 nS; range: 92 to 350 nS) which occurred in two-thirds of the seizures. (4) The conductance values during postictal depression were situated between those measured during the seizure hyperpolarizations and during sleep hyperpolarizations. The conductance decreased exponentially back to the values of the slow sleep oscillation over the total duration of the postictal depression. The data suggest that the major mechanism underlying the "wave"-related hyperpolarizing component of spike-wave seizures relies mainly not on active inhibition, but on a mixture of disfacilitation and potassium currents.

Action Potentials↗

PubMed2000

Integration of low-frequency sleep oscillations in corticothalamic networks.

The corticothalamic system acts as a complex network in promoting the various oscillatory patterns (slow oscillation, spindles, delta) that characterize the state of quiet sleep. Local synchronizing mechanisms of any of the above-mentioned oscillations occur at the site of their genesis, thalamic or cortical. These mechanisms are assisted by the wide-range, synchronized occurrence of the cortical slow oscillation, which finally produces the coalesced picture of slow-wave sleep EEG. Multisite, simultaneous intracellular and field potential recordings in cat, as well as EEG recordings in human were performed in order to assess the state of synchrony and the propagation of various sleep rhythms in the corticothalamic network.

Animals↗

PubMed1999

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.

Animals↗

PubMed1999

Intracellular study of excitability in the seizure-prone neocortex in vivo.

The excitability of neocortical neurons from cat association areas 5-7 was investigated during spontaneously occurring seizures with spike-wave (SW) complexes at 2-3 Hz. We tested the antidromic and orthodromic responsiveness of neocortical neurons during the "spike" and "wave" components of SW complexes, and we placed emphasis on the dynamics of excitability changes from sleeplike patterns to seizures. At the resting membrane potential, an overwhelming majority of neurons displayed seizures over a depolarizing envelope. Cortical as well as thalamic stimuli triggered isolated paroxysmal depolarizing shifts (PDSs) that eventually developed into SW seizures. PDSs could also be elicited by cortical or thalamic volleys during the wave-related hyperpolarization of neurons, but not during the spike-related depolarization. The latencies of evoked excitatory postsynaptic potentials (EPSPs) progressively decreased, and their slope and depolarization surface increased, from the control period preceding the seizure to the climax of paroxysm. Before the occurrence of full-blown seizures, thalamic stimuli evoked PDSs arising from the postinhibitory rebound excitation, whereas cortical stimuli triggered PDSs immediately after the early EPSP. These data shed light on the differential excitability of cortical neurons during the spike and wave components of SW seizures, and on the differential effects of cortical and thalamic volleys leading to such paroxysms. We conclude that the wave-related hyperpolarization does not represent GABA-mediated inhibitory postsynaptic potentials (IPSPs), and we suggest that it is a mixture of disfacilitation and Ca(2+)-dependent K(+) currents, similar to the prolonged hyperpolarization of the slow sleep oscillation.

Animals↗

PubMed1999

Spontaneous and artificial activation of neocortical seizures.

The aim of this study is to disclose the mechanisms underlying the recruitment of neocortical networks during slow-wave sleep oscillations evolving into spike-wave (SW) seizures. 1) We investigated the activation of SW seizures in a seizure-prone neocortex by means of electrical stimuli applied within the frequency range of spontaneous sleep oscillations. Stimuli were grouped in bursts of 10 Hz, similar to sleep spindles, and repeated every 2 s, to reproduce their rhythmic recurrence imposed by the slow (<1 Hz) sleep oscillation. Either cortical or thalamic stimuli, which were applied while the cortex displayed sleeplike activity, gradually induced paroxysmal responses in intracellularly recorded neocortical neurons, which were virtually identical to those of spontaneous seizures and consisted of a progressive buildup of paroxysmal depolarizing shifts (PDSs). 2) The ability of cortical networks to follow stimuli was tested at various stimulation frequencies (1-3 Hz) and quantified by calculating the entropy of the ensuing oscillation. Rhythmic PDSs were optimally induced, and the lowest entropy was generated, at a stimulation frequency around 1.5 Hz. Fast runs at 10-15 Hz, which often override PDSs, thus contributing to the polyspike-wave pattern of seizures, were induced by cortical stimuli, but were disturbed by thalamic stimuli. Spontaneous seizures generally evolved toward an accelerated discharge of PDSs. It is suggested that these accelerating trends during SW seizures act as protective mechanisms by provoking the uncoupling of cortical networks and eventually arresting the seizure.

Animals↗

PubMed1998

Electrophysiological correlates of sleep delta waves.

Recent studies have disclosed several oscillations occurring during resting sleep within the frequency range of the classical delta band (0.5-4 Hz). There are at least 3 oscillations with distinct mechanisms and sites of origin: a slow (<1 Hz) cortically-generated oscillation, a clock-like thalamic oscillation (1-4 Hz), and a cortical oscillation (1-4 Hz). The present paper reviews data on these oscillations and the possible mechanisms which coalesce them into the polymorphic waves of slow wave sleep. Data stem from intracellular (over 500 single cell and 50 double impalements) and field potentials recorded from the cortex and thalamus of cats (120 animals) under ketamine and xylazine anesthesia. Other experiments were based on whole night EEG recordings from humans (5 subjects). The frequency of the slow oscillation both in anesthetized animals and in naturally sleeping humans ranged between 0.1 and 1 Hz (89% of the cases being between 0.5 and 0.9 Hz). The slow (<1 Hz) oscillation is reflected in the EEG as rhythmic sequences of surface-negative waves (associated with hyperpolarizations of deeply-lying neurons) and surface-positive K-complexes (representing excitation in large pools of cortical neurons). Through its long-range synchronization, the slow oscillation has the ability to trigger and to group thalamically-generated spindles and two delta (1-4 Hz) oscillations. Finally, it is argued that the analysis of the electroencephalogram should transcend the spectral analyses, by taking into account the shape of the waves and, when possible, the basic mechanisms that generate those waves.

Animals↗

PubMed1998

Cellular substrates and laminar profile of sleep K-complex.

We describe the cellular mechanisms that underlie the generation of the K-complex, a major grapho-element of sleep electroencephalogram in humans. First we demonstrate the similarity between K-complexes recorded during natural sleep and under ketamine-xylazine anaesthesia in cats. Thereafter, we show by means of multi-site cellular and field potential recordings that K-complexes are rhythmic at frequencies of less than 1 Hz (mainly 0.5-0.9 Hz) and that they are synchronously distributed over the whole cortical surface as well as transferred to the thalamus. The surface K-complex reverses its polarity at a cortical depth of about 0.3 mm. At the cortical depth, the K-complex is made of a sharp and high-amplitude negative deflection that reflects cellular depolarization, often preceded by a smaller-amplitude, positive slow-wave reflecting cellular hyperpolarization. The sharp component of the K-complex may lead to a spindle sequence and/or to fast (mainly 20-50 Hz) oscillations. K-complexes appear spontaneously or triggered by cortical or thalamic stimulation, and they arise within cortical networks. We suggest that K-complexes, either in isolation or followed by a brief sequence of spindle waves, are the expression of the spontaneously occurring, cortically generated slow oscillation.

Algorithms↗

PubMed1998

Slow sleep oscillation, rhythmic K-complexes, and their paroxysmal developments.

This paper presents the relations between the slow (< 1 Hz) oscillation (characterizing the activity of corticothalamic networks during quiescent sleep in cats and humans), sleep K-complexes, and some paroxysmal developments of sleep patterns. At the cellular level, the slow oscillation is built up by rhythmic membrane depolarizations and hyperpolarizations of cortical neurons. The EEG expression of this activity is marked by periodic K-complexes which reflect neuronal excitation. The slow oscillation triggers, groups and synchronizes other sleep rhythms, such as thalamically generated spindles as well as thalamically and cortically generated delta oscillations. We discuss the distinctness of the slow (< 1 Hz) and delta (1-4 Hz) oscillations. We also show that the slow cortical oscillation underlies the onset of spike-wave seizures during sleep by transforming the periodic K-complexes into recurrent paroxysmal spike-wave complexes.

Animals↗

PubMed1998

Spike-wave complexes and fast components of cortically generated seizures. II. Extra- and intracellular patterns.

In the previous paper we have demonstrated, by means of field potential and extracellular unit recordings, that bicuculline-induced seizures, which include spike-wave (SW) or polyspike-wave (PSW) complexes, are initiated intracortically and survive ipsilateral thalamectomy. Here, we used multisite field potential and extracellular recordings to validate the patterns of cortical SW/PSW seizures in chronically implanted, behaving cats. To investigate the cellular patterns and excitability during spontaneously occurring and electrically elicited cortical seizures, we used single and dual intracellular recordings from regular-spiking (RS) and fast-rhythmic-bursting (FRB) cortical neurons, in conjunction with field potential recordings from neocortex and related thalamic nuclei, in cats maintained under ketamine-xylazine anesthesia. 1) Invariably, the spontaneous or electrically induced seizures were initiated within the cortex of both behaving and anesthetized animals. Spontaneously occurring, compound seizures consisting of SW/PSW complexes at 2-4 Hz and fast runs at 10-15 Hz, developed without discontinuity from the slow (mainly 0.5-0.9 Hz), sleeplike, cortically generated oscillation. 2) During SW/PSW complexes, RS neurons discharged spike trains during the depth-negative component of the cortical "spike" component of field potentials and were hyperpolarized during the depth-positive field wave. The FRB neurons fired many more action potentials than RS cells during SW/PSW complexes. Averaged activities triggered by the spiky field potentials or by the steepest slope of depolarization in cortical neurons demonstrated similar relations between intracellular activities and field potentials during sleep and seizure epochs, the latter-being an exaggeration of the depolarizing and hyperpolarizing components of the slow sleep oscillation. 3) During the fast runs, RS cells were tonically depolarized and discharged single action potentials or spike doublets (usually with pronounced spike inactivation), whereas FRB cells discharged rhythmic spike bursts, time locked with the depth-negative field potentials. 4) Neuronal excitability, tested by depolarizing current pulses applied throughout the seizures and compared with pre- and postseizure epochs, showed a decreased number of evoked action potentials during both seizure components (SW/PSW complexes and fast runs), eventually leading to null responses during the postictal depression. 5) Data suggest that interconnected FRB neurons may play an important role in the initiation of cortical seizures. We discuss the similarities between the electrographic patterns described in this study and those found in different forms of clinical seizures.

Anesthesia↗

PubMed1998

Spike-wave complexes and fast components of cortically generated seizures. III. Synchronizing mechanisms.

The intracortical and thalamocortical synchronization of spontaneously occurring or bicuculline-induced seizures, consisting of spike-wave (SW) or polyspike-wave (PSW) complexes at 2-3 Hz and fast runs at 10-15 Hz, was investigated in cats under ketamine-xylazine anesthesia. We used single and dual simultaneous intracellular recordings from cortical areas 5 and 7, and extracellular recordings of unit firing and field potentials from neocortical areas 5, 7, 17, 18, as well as related thalamic nuclei. The evolution of time delays between paroxysmal depolarizing events in single neurons or neuronal pools recorded from adjacent and distant sites was analyzed by using 1) sequential cross-correlations between field potentials, 2) averaged activities triggered by the spiky component of cortical SW/PSW complexes, and 3) time histograms between neuronal discharges. In all instances, the paroxysmal activities recorded from the dorsal thalamus lagged the onset of seizures in neocortex. The time lags between simultaneously impaled cortical neurons were significantly smaller during SW complexes than during the prior epochs of slow oscillation. During seizures, as during the slow oscillation, the intracortical synchrony was reduced with increased distance between different cortical sites. Dual intracellular recordings showed that, during the same seizure, time lags were not constant and, instead, reflected alternating precession of the recorded foci. After transection between areas 5 and 7, the intracortical synchrony was lost, but corticothalamocortical volleys could partially restore seizure synchrony. These data show that the neocortex leads the thalamus during SW/PSW seizures, that time lags between cortical foci are not static, and that thalamus may assist synchronization of SW/PSW seizures after disconnection of intracortical synaptic linkages.

Anesthesia↗

PubMed1998

Coalescence of sleep rhythms and their chronology in corticothalamic networks.

The cellular substrates of sleep oscillations have recently been investigated by means of multi-site, intracellular and extracellular recordings under anesthesia, and these data have been validated during natural sleep in cats and humans. Although various rhythms occurring during the state of resting sleep (spindle, 7-14 Hz; delta, 1-4 Hz; and slow oscillation, <1 Hz) are conventionally described by using their different frequencies, they are coalesced within complex wave-sequences due to the synchronizing power of the cortically generated slow oscillation (main peak around 0.7 Hz). In intracellular recordings from anesthetized animals, the slow oscillation is characterized by a biphasic sequence consisting of a prolonged hyperpolarization and depolarization. Basically similar patterns are observed by means of extracellular discharges and/or field potentials in naturally sleeping animals and humans. The depolarizing component of the slow oscillation is transferred to the thalamus where it contributes to the synchronization of spindles over widespread territories. The association between the depolarizing component of the slow oscillation and the subsequent sequence of spindle waves forms what is termed the K-complex. The slow oscillation also groups cortically generated delta waves. At variance with previous assumptions that the brain lies for the most part in the dark and a global inhibition occurs in resting sleep, cortical cells are quite active in this behavioral state. This unexpectedly rich activity raises the possibility that, during sleep, the brain is occupied to specify/reorganize circuits and to consolidate memory traces acquired during wakefulness.

Anesthesia↗

PubMed1997

Instrumental conditioning of fast (20- to 50-Hz) oscillations in corticothalamic networks.

Cats were instrumentally conditioned to generate grouped fast (20- to 50-Hz) oscillations in motor cortex (area 4). Over seven experimental sessions, there was a spatially selective increased generation of grouped fast oscillations in that electroencephalogram lead. This locally increased generation of fast oscillations in cortex was associated with a widespread increase in synchrony of fast oscillations in thalamocortical networks, as demonstrated by cross-correlations between intracortical, corticothalamic, and intrathalamic field potentials. A three-session extinction period abolished the local increase in generation of grouped fast oscillations and reset the thalamocortical synchrony of fast oscillations to control values. A subsequent series of seven sessions with instrumental conditioning of fast oscillations in visual cortex (area 17) reproduced the results from area 4, with a spatially selective increased generation of grouped fast oscillations in the criterion lead, associated with a widespread increase in thalamocortical synchrony of fast oscillations. In addition to their presence during the conditioning sessions, the changes in synchrony of fast oscillations were expressed during periods of quiet waking, rapid-eye-movement sleep, and nonrapid-eye-movement sleep recorded during the first hour after the end of the conditioning.

Animals↗

PubMed1997

The K-complex: its slow (<1-Hz) rhythmicity and relation to delta waves.

The K-complex is a major graphoelement of sleep EEG. This report demonstrates that K-complexes emerge from a cortically generated slow (<1-Hz) oscillation. Human EEG as well as cat cellular and field potential recordings converge into demonstrating that the K-complex results from a synchronized cortical network that imposes periodic excitatory and inhibitory actions on cortical neurons. We additionally show the correspondence between neuronal activities and the shape of the K-complex. Spectral analysis confirms the periodic recurrence of human K-complexes, with main peaks at 0.5 to 0.7 Hz. It is also shown that the spectral content in the delta band (1 to 4 Hz) is partially due to the shape and duration of the K-complex.

Action Potentials↗