The morphofunctional characteristics of the neurons in the sensorimotor cortex of old rabbits during the trace assimilation of rhythm]

Extracellular neuronal activity was recorded from 460 neurons from alert young (5-7 months), middle-aged (54-65 months) and old (66-85 months) rabbits. Trace rhythmic activity of sensorimotor cortical neurons was examined after long-lasting (10-20 min) rhythmic (0.5-2 Hz) electrocutaneous stimulation of the contralateral forelimb. Spectral analysis of spike activity showed age-related differences in capability of producing a rhythm of previous stimulation in spontaneous neuronal activity. In young animals propriate rhythmic fluctuations of firing rate appeared after the first or second sessions of stimulations (on the first experimental day), in middle-aged ones--after 2-4 sessions (on the second or third days); cortical neurons in old rabbits did not exhibit trace rhythmic activity. Significant morphological changes in glial and neuronal cells were observed in sensorimotor cortex of old rabbits. It is proposed that morphological deteriorations may be the reason of the impairement of trace processes during aging.     

Spontaneous activity of hippocampal neurons and stimulation rhythm acquisition in young rabbits during learning: age features

Ontogenetic mechanisms of memory formation were studied using an experimental model of conditioned reflex to time, i.e., trace acquisition of a stimulation rhythm by hippocampal CA1 neurons of young (1-4 weeks old) and adult rabbits (5-6 months old). It was found that age-related development of learning ability includes several stages: complete absence of memory traces (6-7 days old), rapid acquisition without consolidation (8-14 days old), and formation of perfect memory (25-30 days old). Both specific and nonspecific changes in spontaneous activity of neurons were observed. Changes in the rate of discharges related to rhythmic stimulation were accompanied by changes in spontaneous activity. With the development of an animal, spike activity increased in parallel with improving of the functional properties of neurons, their structural organization, formation of the afferent contacts in the hippocampus completed after a period of three weeks from birth, and formation of metabolic processes, modulatory systems, and traffic function of hippocampal neurons. A capability for plastic reorganization is of great importance for adaptation mechanisms and conditioned behavior of a developing animal in accordance with structural maturation and development of the functional regulation of neuronal reactivity in the hippocampus.     

Inputs from upper airway affect firing of respiratory-associated midbrain neurons

Chen, Zibin, and Frederic L. Eldridge. Inputs fromupper airway affect firing of respiratory-associated midbrain neurons. J. Appl. Physiol. 83(1): 196-203, 1997.In 16 decerebrated unanesthetized cats, we studied effects ofneural inputs from upper airway on firing of 62 mesencephalic neuronsthat also developed respiratory-associated (RA) rhythmic firing whenrespiratory drive was high [Z. Chen, F. L. Eldridge, and P.G.Wagner. J. Physiol. (Lond.) 437:305-325, 1991] and on firing of 16 neurons that did notdevelop the rhythmic firing (non-RA neurons). Activity in RA neuronsincreased after mechanical expansion of pharynx (45% of those tested)or larynx (68%) and after stimulation of glossopharyngeal (50%) orsuperior laryngeal nerves (77%). The increased neuronal firingoccurred despite decreases or abolition of respiratory activity(expressed in phrenic nerve). Neuronal firing also increased aftermechanical stimulation of nasal mucosa (66%) or by jetsof air directed into the nares (48%) and after lightbrushing of nasal skin (~40%). Most stimuli led to decreased firingin a smaller number of neurons, and some neurons showed no response.None of the non-RA neurons developed an increase of firing after any ofthe stimuli, although one had decreased firing after stimulation of thesuperior laryngeal nerve. We conclude that inputs from the upper airwayand nasal skin have independent modulatory effects on the samemesencephalic neurons that are stimulated by ascending rhythmic RAinput from the medulla. These findings may have relevance to generationof the sensation of dyspnea.

     

Self-sustained rhythmic spike and wave activity and response of glial and nerve cells in the cat sensorimotor cortex

During acute experiments on unanesthetized cats, immobilized with myorelaxants, it was found that during rhythmic stimulation (8–14 Hz, duration: 10 sec) of the ventroposterolateral thalamic nucleus brief hyperpolarization is succeeded by depolarization in the pyramidal neurons of the sensorimotor cortex. Following this depolarization, rhythmic (approximately 3 Hz) paroxysmal depolarizing shifts in membrane potential are produced by ending stimulation, succeeded by protracted hyperpolarization and termination of rhythmic wave activity. Depolarization only is observed in glial cells, however, while hyperpolarization sets in after hyperpolarization is completed in the neurons. It is suggested that long-term changes in the membrane potential of cortical cells could make some contribution to the setting up and termination of rhythmic spike and wave activity.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 319–325, May–June, 1986.     

Search for cerebral G cluster neurons responding to taste stimulation with seaweed in Aplysia kurodai by the use of calcium imaging

The calcium imaging method can detect the spike activities of many neurons simultaneously. In the present experiments, this method was used to search for unique neurons contributing to feeding behavior in the cerebral ganglia of Aplysia kurodai. We mainly explored the neurons whose cell bodies were located in the G cluster and the neuropile region posterior to this cluster on the ventral surface of the cerebral ganglia. When the extract of the food seaweed Ulva was applied to the tentacle-lip region, many neurons stained with a calcium-sensitive dye, Calcium Green-1, showed changes in fluorescence. Some neurons showed rhythmic responses and others showed transient responses, suggesting that these neurons may be partly involved in the feeding circuits. We also identified three motor neurons among these neurons that showed rhythmic fluorescence responses to the taste stimulation. One of them was a motor neuron shortening the anterior tentacle (ATS), and the other two were motor neurons producing lip opening-like (LO(G)) and closing-like (LC(G)) movements, respectively. Application of the Ulva extract to the tentacle-lip region induced phase-locked rhythmic firing activity in these motor neurons, suggesting that these neurons may contribute to the rhythmic patterned movements of the anterior tentacles and lips during the ingestion of seaweed.     

延髓头端腹外侧区神经元电活动与心血管活动相干性的研究

本文分析了大鼠延头端腹外侧区（ＲＶＬＭ）神经元单位活动与心血管活动的相干性,观察了ＲＶＬＭ区神经元电 对电刺激中脑防御反应区的诱发反应,以及对压力感受性反射的反应,并用ＦＦＴ对ＲＶＬＭ区神经元自发单位放电和血压波进行频域的相干性分析,以判断是具有心节律。还分析了ＲＶＬＭ区单位放电变异性与心率变异性的相干性。结果显示：ＲＶＬＭ区大多数神经元对电刺激中脑防御反应区呈兴奋反应（６７％）,７０％神经元放电     

Trace rhythm recruitment by the neurons of the rabbit sensorimotor cortex in old age]

Spectral analysis (ACG and gSP) of the impulse activity of the neurones of the old rabbits sensorimotor cortex allowed to reveal a trace recruitment of the rhythm--CR analogue to time--in after-action f rhythmic stimulation. Connection was established between the number of presented series of periodic electrocutaneous stimulation and expressiveness of the trace rhythm recruitment depending on the animals age. Trace rhythm recruitment took place slower in old animals (54-56 months) than in young ones (up to 1 year), chiefly in 2-3 experimental days after 2-4 series of rhythmic stimulation and was preserved in a small percent of cases the next day after stimulation. In the background activity of a number of neurones an initial periodicity was discovered, which was intensified under the influence of stimulation by another frequency, or the initial rhythm was extinguished, and stimulation rhythm was reproduced. Periodical stimulation in very old animals (66-85 months) practically did not evoke plastic reconstructions of the cortical neurones. Under the influence of the stimulation a non-specific trace increase of the frequency of neurones background activity of the old animals was observed. The revealed characteristics of plastic neurones properties may testify to projected disturbances of mnestic processes at definite age stages of normal aging.     

Rhythmic activity of neurons in the rostral ventrolateral medulla of conscious cats: effect of removal of vestibular inputs

Although it is well established that bulbospinal neurons located in the rostral ventrolateral medulla (RVLM) play a pivotal role in regulating sympathetic nerve activity and blood pressure, virtually all neurophysiological studies of this region have been conducted in anesthetized or decerebrate animals. In the present study, we used time- and frequency-domain analyses to characterize the naturally occurring discharges of RVLM neurons in conscious cats. Specifically, we compared their activity to fluctuations in carotid artery blood flow to identify neurons with cardiac-related (CR) activity; we then considered whether neurons with CR activity also had a higher-frequency rhythmic firing pattern. In addition, we ascertained whether the surgical removal of vestibular inputs altered the rhythmic discharge properties of RVLM neurons. Less than 10% of RVLM neurons expressed CR activity, although the likelihood of observing a neuron with CR activity in the RVLM varied between recording sessions, even when tracking occurred in a very limited area and was higher after vestibular inputs were surgically removed. Either a 10-Hz or a 20- to 30-Hz rhythmic discharge pattern coexisted with the CR discharges in some of the RVLM neurons. Additionally, the firing rate of RVLM neurons, including those with CR activity, decreased after vestibular lesions. These findings raise the prospect that RVLM neurons may or may not express rhythmic firing patterns at a particular time due to a variety of influences, including descending projections from higher brain centers and sensory inputs, such as those from the vestibular system.     

Spiking neurons that keep the rhythm

Detecting the temporal relationship among events in the environment is a fundamental goal of the brain. Following pulses of rhythmic stimuli, neurons of the retina and cortex produce activity that closely approximates the timing of an omitted pulse. This omitted stimulus response (OSR) is generally interpreted as a transient response to rhythmic input and is thought to form a basis of short-term perceptual memories. Despite its ubiquity across species and experimental protocols, the mechanisms underlying OSRs remain poorly understood. In particular, the highly transient nature of OSRs, typically limited to a single cycle after stimulation, cannot be explained by a simple mechanism that would remain locked to the frequency of stimulation. Here, we describe a set of realistic simulations that capture OSRs over a range of stimulation frequencies matching experimental work. The model does not require an explicit mechanism for learning temporal sequences. Instead, it relies on spike timing-dependent plasticity (STDP), a form of synaptic modification that is sensitive to the timing of pre- and post-synaptic action potentials. In the model, the transient nature of OSRs is attributed to the heterogeneous nature of neural properties and connections, creating intricate forms of activity that are continuously changing over time. Combined with STDP, neural heterogeneity enabled OSRs to complex rhythmic patterns as well as OSRs following a delay period. These results link the response of neurons to rhythmic patterns with the capacity of heterogeneous circuits to produce transient and highly flexible forms of neural activity.     

Activity of propriospinal neurons in segments C3 and C4 during fictitious locomotion in cats

Activity of propriospinal neurons in segments C3 and C4 was recorded in immobilized decerebrate cats, whose spinal cord was divided at the lower thoracic level, during locomotor activity of neuronal mechanisms controlling the forelimbs (fictitious locomotion of the forelimbs). Neurons were identified according to antidromic responses to stimulation of the lateral column of the spinal cord at level C6. Antidromic responses also appeared in 70% of these neurons to stimulation of the medullary lateral reticular nucleus. During fictitious locomotion, i.e., in the absence of afferent signals from the limb receptors, rhythmic modulation of the discharge of most neurons was observed, correlating with activity of motoneurons. If the rostral region of the cervical enlargement of the spinal cord was cooled, causing generation of the locomotor rhythm to cease, rhythmic activity of propriospinal neurons in segments C3 and C4 also ceased. The main source of modulation of activity of propriospinal neurons in segments C3 and C4 is thus the central spinal mechanisms controlling activity of the forelimbs.Institute for Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov Moscow University. Translated from Neirofiziologiya, Vol. 17, No. 3, pp. 320–326, May–June, 1985.     

Postsynaptic neuronal response of a cat sensorimotor cortex during evoked and self-sustained rhythmic "spike and wave" activity

Intracellular correlates of complex sets of rhythmic cortical "spike and wave" potentials evoked in sensorimotor cortex and of self-sustained rhythmic "spike and wave" activity were examined during acute experiments on cats immobilized by myorelaxants. Rhythmic spike-wave activity was produced by stimulating the thalamic relay (ventroposterolateral) nucleus (VPLN) at the rate of 3 Hz; self-sustained afterdischarges were recorded following 8–14 Hz stimulation of the same nucleus. Components of the spike and wave afterdischarge mainly correspond to the paroxysmal depolarizing shifts of the membrane potential of cortical neurons in length. After cessation of self-sustained spike and wave activity, prolonged hyperpolarization accompanied by inhibition of spike discharges and subsequent reinstatement of background activity was observed in cortical neurons. It is postulated that the negative slow wave of induced spike and wave activity as well as slow negative potentials of direct cortical and primary response reflect IPSP in more deep-lying areas of the cell bodies, while the wave of self-sustained rhythmic activity is due to paroxysmal depolarizing shifts in the membrane potential of cortical neurons.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 298–306, May–June, 1986.     

Stimulation of the hippocampus and its effect on electrographic manifestations of the brain in unrestrained rats.

The dorsal hippocampus was electrically stimulated in unanaesthetized, unrestrained rats with a cobalt-gelatin rod in their cortex. The significance of the hippocampus in the elicitation of both physiological spontaneous rhythmic activity (episodic activity of 8--9/sec frequency bound, in rats, to a state of quiet wakefulness, and "sleep spindles") and pathological rhythmic activity of the self-sustained after-discharge (SSAD) type was determined from the aspect of the EEG and behavioural characteristics. 1. Single electrical pulses (0.1 msec, 1--10 V, 0.3/sec) elicited an evoked potential bilaterally in the somatosensory cortex. Elicitation of rhythmic after-activity (of the type of episodes or sleep spindles) was observed only in some cases in which an adequately strong stimulus was used. 2. Repeated series of rhythmic electrical stimuli following each other at short intervals (2--3 min) led to the formation of SSAD in about one third of the cases and at all stimulation frequencies (3-15/sec), although low frequencies (3--4/sec) were the least effective. The character of the SSAD and simultaneous behavioural phenomena differed fundamentally from those evoked by electrical stimulation of the thalamus (Chocholová et al. 1977). The development of paroxysmal after-activity was signalled by responses of a more or less distinct "recruiting" character during stimulation. On the basis of a comparison of electrographic and behavioural manifestations after electrical stimulation of the thalamus and hippocampus, the possibility of both thalamic and extrathalamic projection from the hippocampus to the cortical region is considered.     

Two patterns of bulbar neuronal response to microstimulation of locomotor and inhibitory brain stem sites

Synaptic responses (postsynaptic potentials and action potentials) were evoked in mesencephalic decerebellated cats by stimulating pontine bulbar locomotor and inhibitory sites (LS and IS, respectively) with a current of not more than 20 µA in "medial" and "lateral" neurons of the medulla. Some neurons even produced a response to presentation of single (actually low — 2–5 Hz — frequency) stimuli. The remaining cells responded to stimulation at a steady rate of 30–60 Hz only. Both groups of medial neurons were more receptive to input from LS. Lateral neurons responding to even single stimuli reacted more commonly to input from LS and those responding to steady stimulation only to input from IS. Many neurons with background activity (whether lateral or medial) produced no stimulus-bound response, but rhythmic stimulation either intensified or inhibited such activity. This response occurs most commonly with LS stimulation. Partial redistribution of target neurons in step with increasing rate of presynaptic input may play a major part in control of motor activity.Institute for Research into Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 257–266, March–April, 1990.     

Modelling Feedback Excitation,Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity

What cellular and network properties allow reliable neuronal rhythm generation or firing that can be started and stopped by brief synaptic inputs? We investigate rhythmic activity in an electrically-coupled population of brainstem neurons driving swimming locomotion in young frog tadpoles, and how activity is switched on and off by brief sensory stimulation. We build a computational model of 30 electrically-coupled conditional pacemaker neurons on one side of the tadpole hindbrain and spinal cord. Based on experimental estimates for neuron properties, population sizes, synapse strengths and connections, we show that: long-lasting, mutual, glutamatergic excitation between the neurons allows the network to sustain rhythmic pacemaker firing at swimming frequencies following brief synaptic excitation; activity persists but rhythm breaks down without electrical coupling; NMDA voltage-dependency doubles the range of synaptic feedback strengths generating sustained rhythm. The network can be switched on and off at short latency by brief synaptic excitation and inhibition. We demonstrate that a population of generic Hodgkin-Huxley type neurons coupled by glutamatergic excitatory feedback can generate sustained asynchronous firing switched on and off synaptically. We conclude that networks of neurons with NMDAR mediated feedback excitation can generate self-sustained activity following brief synaptic excitation. The frequency of activity is limited by the kinetics of the neuron membrane channels and can be stopped by brief inhibitory input. Network activity can be rhythmic at lower frequencies if the neurons are electrically coupled. Our key finding is that excitatory synaptic feedback within a population of neurons can produce switchable, stable, sustained firing without synaptic inhibition.     

The neuronal organization of the dentate nucleus of the cerebellum

The intracellular activity of the neurons of the dentate nucleus was studied in cats anesthetized with Nembutal by means of their antidromic and synaptic excitation through stimulation of the red nucleus (RN) and the ventrolateral nucleus of the thalamus (VL), as well as the sensomotor cerebral cortex (CC) and the peripheral nerves of the posterior and anterior extremities. Several functionally delimited groups of neurons were isolated and studied. Efferent neurons, antidromically activated from nuclei of the brain stem, which did not react to stimulation of the peripheral nerves were placed in group I. Group II neurons were synaptically activated from the nuclei of the brain stem, and in a majority of cases also reacted to stimulation of the peripheral nerves and CC. Cells with a rhythmic background activity, which did not react to any of the types of stimulation used, comprised group III. Group IV was made up of neurons having the properties of intermediate neurons with a selective reaction to stimulation of a specific peripheral nerve or which experience broad convergence of the effects of different afferent impulsations.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 3, No. 2, pp. 154–165, March–April, 1971.     

Dynamics of driven rhythm in neuronal assemblies in sensorimotor and visual cerebral cortices in rabbit

Coincident activity of pairs of neurons in the sensorimotor and visual areas of the cerebral cortex was studied in naive, learning, and trained rabbits during the formation of a hidden excitation focus in their central nervous system (a defensive dominanta) of the rhythmic nature. In the trained rabbits (as compared to the naive animals), percent of neuronal pairs (both neighboring and distant) in whose coincident activity the rhythm of stimulation prevailed was higher. In the visual cortex, percent of such pairs was significantly higher only for the distant neurons. Analysis of interaction between neurons in the visual and sensorimotor cortices revealed increasing the number of neuronal pairs with the driven rhythm while training. Such an increase was observed when both sensorimotor and visual neurons were considered as leading.     

mPer2 antisense oligonucleotides inhibit mPER2 expression but not circadian rhythms of physiological activity in cultured suprachiasmatic nucleus neurons

Various day-night rhythms, observed at molecular, cellular, and behavioral levels, are governed by an endogenous circadian clock, predominantly functioning in the hypothalamic suprachiasmatic nucleus (SCN). A class of clock genes, mammalian Period (mPer), is known to be rhythmically expressed in SCN neurons, but the correlation between mPER protein levels and autonomous rhythmic activity in SCN neurons is not well understood. Therefore, we blocked mPer translation using antisense phosphothioate oligonucleotides (ODNs) for mPer1 and mPer2 mRNAs and examined the effects on the circadian rhythm of cytosolic Ca2+ concentration and action potentials in SCN slice cultures. Treatment with mPer2 ODNs (20microM for 3 days) but not randomized control ODNs significantly reduced mPER2 immunoreactivity (-63%) in the SCN. Nevertheless, mPer1/2 ODNs treatment inhibited neither action potential firing rhythms nor cytosolic Ca2+ rhythms. These suggest that circadian rhythms in mPER protein levels are not necessarily coupled to autonomous rhythmic activity in SCN neurons.     

Activity of propriospinal neurons during the scratch reflex in cats

Fictitious scratching, i.e., rhythmic activity of hind-limb motoneurons at the characteristic scratching frequency, was evoked by tactile stimulation of the ear in thalamic cats immobilized with flaxedil. Activity of propriospinal neurons in segments C₁, C₂, and T₄–T₇ was recorded extracellularly. The neurons were identified by their antidromic response to stimulation of their axons in segment L₁. Most neurons did not respond to stimulation of the ear. Some neurons, however, were activated during fictitious scratching. Neurons of the cervical segments responded not only to stimulation of the ear, but also to tactile stimulation of the forelimbs and also to passive movements of those limbs. Neurons of the thoracic segments were activated only by stimulation of the ipsilateral ear; these neurons were inhibited by stimulation of the contralateral ear. The role of the propriospinal neurons in the activation of the spinal mechanisms of scratching is discussed.Institute for Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 9, No. 5, pp. 504–511, September–October, 1977.     

Function of the Shaw potassium channel within the Drosophila circadian clock

Background

In addition to the molecular feedback loops, electrical activity has been shown to be important for the function of networks of clock neurons in generating rhythmic behavior. Most studies have used over-expression of foreign channels or pharmacological manipulations that alter membrane excitability. In order to determine the cellular mechanisms that regulate resting membrane potential (RMP) in the native clock of Drosophila we modulated the function of Shaw, a widely expressed neuronal potassium (K⁺) channel known to regulate RMP in Drosophila central neurons.

Methodology/Principal Findings

We show that Shaw is endogenously expressed in clock neurons. Differential use of clock gene promoters was employed to express a range of transgenes that either increase or decrease Shaw function in different clusters of clock neurons. Under LD conditions, increasing Shaw levels in all clock neurons (LNv, LNd, DN₁, DN₂ and DN₃), or in subsets of clock neurons (LNd and DNs or DNs alone) increases locomotor activity at night. In free-running conditions these manipulations result in arrhythmic locomotor activity without disruption of the molecular clock. Reducing Shaw in the DN alone caused a dramatic lengthening of the behavioral period. Changing Shaw levels in all clock neurons also disrupts the rhythmic accumulation and levels of Pigment Dispersing Factor (PDF) in the dorsal projections of LNv neurons. However, changing Shaw levels solely in LNv neurons had little effect on locomotor activity or rhythmic accumulation of PDF.

Conclusions/Significance

Based on our results it is likely that Shaw modulates pacemaker and output neuronal electrical activity that controls circadian locomotor behavior by affecting rhythmic release of PDF. The results support an important role of the DN clock neurons in Shaw-mediated control of circadian behavior. In conclusion, we have demonstrated a central role of Shaw for coordinated and rhythmic output from clock neurons.     

Transcranial alternating current stimulation enhances individual alpha activity in human EEG

Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity.The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex. The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application.