Spontaneous Activity Of Single Neurons Research Articles

Fractal analysis reveals subclasses of neurons and suggests an explanation of their spontaneous activity

The present work used fractal time series analysis (detrended fluctuation analysis; DFA) to examine the spontaneous activity of single neurons in an anesthetized animal model, specifically, the mitral cells in the rat main olfactory bulb. DFA bolstered previous research in suggesting two subclasses of mitral cells. Although there was no difference in the fractal scaling of the interspike interval series at the shorter timescales, there was a significant difference at longer timescales. Neurons in Group B exhibited fractal, power-law scaled interspike intervals, whereas neurons in Group A exhibited random variation. These results raise questions about the role of these different cells within the olfactory bulb and potential explanations of their dynamics. Specifically, self-organized criticality has been proposed as an explanation of fractal scaling in many natural systems, including neural systems. However, this theory is based on certain assumptions that do not clearly hold in the case of spontaneous neural activity, which likely reflects intrinsic cell dynamics rather than activity driven by external stimulation. Moreover, it is unclear how self-organized criticality might account for the random dynamics observed in Group A, and how these random dynamics might serve some functional role when embedded in the typical activity of the olfactory bulb. These theoretical considerations provide direction for additional experimental work.

Effect of cortex inactivation on spontaneous activity of cells in perigeniculate and dorsal lateral geniculate nuclei

The cortical influence on spontaneous activity of single neurons in the dorsal lateral geniculate (LGN) and perigeniculate (PGN) nuclei were investigated in awake cats by means of reversible cooling of cortical areas 17 and 18 [1]. We analyzed subtle changes of the statistical properties of spike trains. To understand their nature we investigated statistics of firing rate (FR), mean inter-spike interval (ISI), bursting rate (BR), mean intra-burst inter-spike interval (IBISI), mean number of spikes per burst (SPB) and mean burst duration (BD)[2,3]. These results indicate that recurrent inhibition from PGN may play a homeostatic role in the cortico-thalamic loop by restricting thalamic oscillations within their natural functional range [4]. The buffering role of PGN may explain why the massive, direct cortical projection to LGN neurons induces only small, highly-tuned effects during spontaneous activity. The BR, FR and IBISI measures of spontaneous activity of PGN cells as a result of cortex cooling increased more than 50% of their original values and more than 20% for SPB while the changes of LGN activity were below 20% for all measures except ISI, which was the only case where the changes were larger in LGN than in the PGN cells (Figure ​(Figure1A).1A). The changes of values taken by all the measures used to quantify activity of LGN (except mean ISI) were statistically significant for less than 30% of investigated neurons, in the case of PGN all the changes except for BD were significant for more than 40% of neurons (Figure ​(Figure1B1B). Figure 1 Effect of cortex cooling on activity of PGN and LGN cells. A. Percent of change in relation to situation when the cortex was active. B. Percent of significant differences (p < 0.05). IBISI - intra burst ISI, SPB - spikes per burst, BD - burst ...

Acoustic trauma evokes hyperactivity and changes in gene expression in guinea‐pig auditory brainstem

Hearing loss from acoustic trauma is a risk factor for tinnitus. Animal models using acoustic trauma have demonstrated hyperactivity in central auditory pathways, which has been suggested as a substrate for tinnitus. We used a guinea-pig model of unilateral acoustic trauma. Within the same animals, measurements of peripheral hearing loss, spontaneous activity of single neurons in the inferior colliculus and gene expression in cochlear nucleus and inferior colliculus were combined, acutely and after recovery from acoustic trauma. Genes investigated related to inhibitory (GABA-A receptor subunit alpha 1; glycine receptor subunit alpha 1) and excitatory neurotransmission (glutamate decarboxylase 1; glutamate receptor AMPA subunit alpha 2; glutamate receptor NMDA subunit 1), regulation of transmitter release (member of RAB family of small GTPase; RAB3 GTPase activating protein subunit 1) and neuronal excitability (potassium channel subfamily K member 15). Acoustic trauma resulted in unilateral hearing loss and hyperactivity bilaterally in inferior colliculus. Changes in expression of different mRNAs were observed in ipsilateral cochlear nucleus and in ipsi- and contralateral inferior colliculus, immediately after acoustic trauma, and after 2 and 4 weeks' recovery. Gene expression was generally reduced immediately after trauma, followed by a return to near normal levels or over-expression as recovery time increased. Different mechanisms appear to underlie the spontaneous hyperactivity observed. There is evidence of down-regulation of genes associated with neuronal inhibition in the contralateral inferior colliculus, whereas in ipsilateral cochlear nucleus, competing actions of inhibitory and excitatory systems seem to play a major role in determining overall excitability.

Microiontophoretically Applied PACAP Blocks Excitatory Effects of Kainic Acid in Vivo

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to be neuroprotective in animal models of different brain pathologies, including focal and global cerebral ischemia. The application of glutaminergic excitotoxin kainic acid (KA), similar to ischemic events, may lead to neurodegeneration. In the present article, we investigated the effects of microiontophoretic application of PACAP on the excitatory effects of KA. During recording-maintained spontaneous activity of single neurons, we microiontophoretized KA, which was followed by the application of PACAP-38. We found that PACAP could block the excitatory effects of KA in several brain areas (cortex: 89%, hippocampus: 36%, and thalamus: 50%). Moreover, we detected a lower level excitatory effect of PACAP alone (41%). The present results may explain the neuroprotective effects of PACAP observed in experimental models of glutamate (GLU)-receptor-mediated degenerative processes.

Linking spontaneous activity of single cortical neurons and the underlying functional architecture.

The relation between the activity of a single neocortical neuron and the dynamics of the network in which it is embedded was explored by single-unit recordings and real-time optical imaging. The firing rate of a spontaneously active single neuron strongly depends on the instantaneous spatial pattern of ongoing population activity in a large cortical area. Very similar spatial patterns of population activity were observed both when the neuron fired spontaneously and when it was driven by its optimal stimulus. The evoked patterns could be used to reconstruct the spontaneous activity of single neurons.

Effect of the group II metabotropic glutamate agonist, 2R,4R-APDC, varies with age, layer, and visual experience in the visual cortex.

Group II metabotropic glutamate receptors (mGluR 2/3) are distributed differentially across the layers of cat visual cortex, and this distribution varies with age. At 3-4 wk, mGluR 2/3 receptor immunoreactivity is present in all layers. By 6-8 wk of age, it is still present in extragranular layers (2, 3, 5, and 6) but has disappeared from layer 4, and dark-rearing postpones the disappearance of Group II receptors from layer 4. We examined the physiological effects of Group II activation, to see if these effects varied similarly. The responses of single neurons in cat primary visual cortex were recorded to visual stimulation, then the effect of iontophoresis of 2R,4R-4 aminopyrrolidine-2, 4-decarboxylate (2R,4R-APDC), a Group II specific agonist, was observed in animals between 3 wk and adulthood. The effect of 2R, 4R-APDC was generally suppressive, reducing both the visual response and spontaneous activity of single neurons. The developmental changes were in agreement with the immunohistochemical results: 2R, 4R-APDC had effects on cells in all layers in animals of 3-4 wk but not in layer 4 of animals >6 wk old. Moreover, the effect of 2R, 4R-APDC was reduced in the cortex of older animals (>22 wk). Dark-rearing animals to 47-54 days maintained the effects of 2R, 4R-APDC in layer 4. The disappearance of Group II mGluRs from layer 4 between 3 and 6 wk of age is correlated with the segregation of ocular dominance columns in that layer, raising the possibility that mGluRs 2/3 are involved in this process.

Coherent spatiotemporal patterns of ongoing activity revealed by real-time optical imaging coupled with single-unit recording in the cat visual cortex.

1. We examined the spatiotemporal organization of ongoing activity in cat visual areas 17 and 18, in relation to the spontaneous activity of individual neurons. To search for coherent activity, voltage-sensitive dye signals were correlated with the activity of single neurons by the use of spike-triggered averaging. In each recording session an area of at least 2 x 2 mm of cortex was imaged, with 124 diodes. In addition, electrical recordings from two isolated units, the local field potential (LFP) from the same microelectrodes, and the surface electroencephalogram (EEG) were recorded simultaneously. 2. The optical signals recorded from the dye were similar to the LFP recorded from the same site. Optical signals recorded from different cortical sites exhibited a different time course. Therefore real-time optical imaging provides information that is equivalent in many ways to multiple-site LFP recordings. 3. The spontaneous firing of single neurons was highly correlated with the optical signals and with the LFP. In 88% of the neurons recorded during spontaneous activity, a significant correlation was found between the occurrence of a spike and the optical signal recorded in a large cortical region surrounding the recording site. This result indicates that spontaneous activity of single neurons is not an independent process but is time locked to the firing or to the synaptic inputs from numerous neurons, all activated in a coherent fashion even without a sensory input. 4. For the cases showing correlation with the optical signal, 27-36% of the optical signal during spike occurrence was directly related to the occurrence of spontaneous spikes in a single neuron, over an area of 2 x 2 mm. In the same cortical area, 43-55% of the activity was directly related to the visual stimulus. 5. Surprisingly, we found that the amplitude of this coherent ongoing activity, recorded optically, was often almost as large as the activity evoked by optimal visual stimulation. The amplitude of the ongoing activity that was directly and reproducibly related to the spontaneous spikes of a single neuron was, on average, as high as 54% of the amplitude of the visually evoked response that was directly related to optimal sensory stimulation, recorded optically. 6. Coherent activity was detected even at distant cortical sites up to 6 mm apart.(ABSTRACT TRUNCATED AT 400 WORDS)

Time series analysis of spontaneous activity of single neurons in the cat olfactory bulb : Yoichi Ogawa and Fumiaki Motokizawa, Department of physiology, Nara Medical College, Kashihara, Nara 634, Japan

Time series analysis of spontaneous activity of single neurons in the cat olfactory bulb : Yoichi Ogawa and Fumiaki Motokizawa, Department of physiology, Nara Medical College, Kashihara, Nara 634, Japan

Time series analysis of spontaneous activity of single neurons in the cat olfactory bulb

Time series analysis of spontaneous activity of single neurons in the cat olfactory bulb

Effects of 5-hydroxytryptamine on the firing rates of neurons of the lateral vestibular nucleus in the rat

5-hydroxytryptamine (5-HT) was delivered microiontophoretically (20-80 nA) to cells of the lateral vestibular nucleus of anaesthetized rats to test its influence on the spontaneous activity of single neurons. 5-HT increased the rate of firing of 94% of the units tested. The enhancement persisted for up to 700 s after the end of the 5-HT ejection and the maximum magnitude of the excitation (10-3400%) showed a hyperbolic correlation (rho = 0.86) with background firing. In 43% of units the enhancement was preceded by a short-lasting (less than 105 s) depression of the neuronal firing rate, the magnitude of which was unrelated to the background mean firing rate. Both components of the 5-HT response were dose-dependent. Only the excitatory responses were antagonized by metergoline, methysergide and ketanserin. The putative 5-HT agonist, 5-methoxy-N,N-dimethyltryptamine, applied microiontophoretically, depressed the background firing rate and was not antagonized by methysergide. These results demonstrate that 5-HT modifies the responsiveness of vestibular neurons and suggest that at least two mechanisms and maybe two types of receptors are activated by 5-HT in this nucleus.

Functional stability of the brain slices of ground squirrels, Citellus undulatus, kept in conditions of prolonged deep periodic hypothermia: Electrophysiological criteria

The brain of hibernating animals, controlling the physiological functions during the hibernation cycles, is itself subject to deep cooling during bouts of hibernation. This suggests its high tolerance to deep hypothermia. Effects of prolonged deep cooling were investigated in hippocampal and septal slices, taken from the brains of three groups of animals: hibernating ground squirrels, actively waking ground squirrels, and guinea-pigs. The slices were kept at a low temperature (2–4°C) for various periods of time (from several hours up to six days) and periodically tested in warm (31°C) incubation medium. The hippocampal field potentials (mainly of field CA1), as well as spontaneous activity of single neurons of hippocampus and medial septum were recorded. For comparative purposes mean amplitudes of population spikes and mean frequency of spontaneous neuronal discharge were used. Significant differences between the experimental groups were observed in recovery of functional activity of the slices after their dissection from the brain, as well as after deep cooling. In both cases re-establishment of neuronal activity in ground squirrels occurred more rapidly, than in guinea-pigs. The most dramatic was the difference in maximal time of survival of the slices under conditions of deep cooling. Independently of periodicity of the electrophysiological testing in warm medium, the slices taken from hibernating squirrels retained their activity for seven to nine days, the slices of waking ground squirrel hippocampus survived up to six to seven days, while those of guinea-pigs did not recover their functional activity after cooling for more than one to two days. Statistically significant increases in amplitude of hippocampal population spikes and in mean frequency of septal neuronal activity was observed before their terminal disintegration (on the sixth and seventh days, respectively). Long-term potentiation could be evoked in the hippocampal slices of ground squirrels six days after their preparation. The hippocampal subdivisions varied in their ability to survive and retain functional activity in the following way: dentate fascia <CA3 <CA1. The data show high adaptive properties of the brain tissue of hibernating animals. The possible functional significance of the observed characteristics is discussed.

An animal model for tinnitus.

Subjective tinnitus remains obscure, widespread, and without apparent cure. In the absence of a suitable animal model, past investigations took place in humans, resulting in studies that were understandably restricted by the nature of human investigation. Within this context, the development of a valid animal model would be considered a major breakthrough in this field of investigation. Our results showed changes in the spontaneous activity of single neurons in the inferior colliculus, consistent with abnormally increased neuronal activity within the auditory pathways after manipulations known to produce tinnitus in man. A procedure based on a Pavlovian conditioned suppression paradigm was recently developed that allows us to measure tinnitus behaviorally in conscious animals. Accordingly, an animal model of tinnitus is proposed that permits tests of hypotheses relating to tinnitus generation, allowing the accommodation of interventional strategies for the treatment of this widespread auditory disorder.

Threshold effects of N-methyl D-aspartate (NMDA) and 2-amino 5-phosphono valeric acid (2APV) on the spontaneous activity of neocortical single neurones in the urethane anaesthetised rat.

Spontaneous activity of single neurones in neocortex was sampled using pairs of microelectrodes in rats anaesthetised with urethane. In confirmation of previous studies, many cells recorded from middle layers characteristically fired in bursts, the onset times of which were synchronous both unilaterally and bilaterally. Iontophoresis of 2APV onto such cells either caused an abolition of bursts or a reduction in spikes per burst. In the latter case action potentials which occurred later in the burst were preferentially abolished. Iontophoresis of NMDA onto the same cells caused a prolongation of bursts with minimal effect on intraburst interspike interval. In interactive trials with the two drugs the effect of NMDA could be abolished by 2APV, and NMDA counteracted the effect of 2APV. It is concluded that spontaneous burst generation in neocortex during urethane anaesthesia is generated through a cortical NMDA/2APV-sensitive receptor mechanism.

Ontogeny of the levels of serotonin in various parts of the brain in severely protein malnourished rats

We have previously reported that irreversible central and peripheral chemical changes and irreversible changes in spontaneous activity of single neurons in the frontal cortex are seen in adult rats who were born to mothers fed an 8% isocaloric casein diet 5 weeks before mating and during gestation, who were cross-fostered at birth by control (25% casein diet fed) dams and who showed a normal growth curve. Thus, in the rat, a normal growth curve does not necessarily mean a normal development. We now report similar irreversible, albeit larger, changes in small-for-gestational-age (SGA) rats born to mothers fed a 6% isocaloric diet, nursed by 6% casein fed dams and who showed an abnormal growth curve. The regional ontogeny of serotonin, tryptophan and 5-HIAA in the brain and plasma levels of tryptophan, protein, albumin and NEFA are reported. Thus, similar changes were observed in animals with a normal growth curve and in animals with a very markedly decreased growth curve resembling marasmus in humans.

Formula omitted] recording of raphe unit activity: Evidence for endogenous rhythms in presumed serotonergic neurons

The spontaneous activity of single neurons in the nucleus raphe dorsalis was recorded in vitro in mouse brain slices. The neurons displayed the slow and regular discharge pattern characteristics of raphe neurons recorded in vivo . When magnesium ion was added to increase the medium concentration to 20–30 mM for the purpose of inhibiting all synaptic transmission, raphe neurons continued to display the same discharge pattern and rate. The data suggest that the steady rhythmic firing of nucleus raphe dorsalis neurons is generated by an intracellular pacemaker mechanism.

Brain stem neuronal types with activity patterns related to sympathetic nerve discharge.

The relationships among the spontaneous activity of single neurons in the cat medulla and inferior cardiac sympathetic nerve discharge (SND), electroencephalogram (EEG) activity, phrenic nerve activity, and the R wave of the electrocardiogram were studied with the methods of spike-triggered averaging and postevent interval analysis. Three categories of neurons (SR, SE, and S) with activity patterns related to SND wee identified. The activity of SR units was related in time to SND and the R wave but not to EEG activity. SE unit discharges were related to SND and EEG activity but not to the R wave. S unit activity was related only to SND. Each of the three categories of neurons could be subdivided into two groups depending on whether their discharges were followed by an increase or a decrease in SND. All unit types exhibited respiratory-related discharge patterns. These data are discussed with regard to the problems associated with the identification of neurons in brain stem networks that govern the discharges of sympathetic nerves.

Benzodiazepines attenuate single unit activity in the locus coeruleus

Several classes of anxiolytic compounds have the common effect of decreasing the firing of noradrenergic neurons or attenuating the post- synaptic effects of noradrenergic activity. In order to determine whether the benzodiazepines, the most widely used anxiolytics, also decrease noradrenergic activity, the effect of acute intravenous injections of diazepam (0.1–2.0 mg/kg) and chlordiazepoxide (0.5–4.0 mg/kg) were administered to anesthetized rats while spontaneous activity of single neurons in the principal noradrenergic nucleus, the locus coeruleus, was recorded. Diazepam and chlordiazepoxide decreased spontaneous single unit activity in the locus coeruleus at relatively low doses. This net effect on noradrenergic systems is consistent with the actions of several classes of nonbenzodiazepine anxiolytics, and with the involvement of noradrenergic systems in the neural mechanisms of anxiety.

Pneumotaxic area neuronal discharge during sleep-waking states in the cat

We examined the spontaneous activity of single neurons within the nucleus parabrachialis medialis (NPBM; pneumotaxic center) of unanesthetized, unrestrained cats in relation to the respiratory cycle during different sleep-waking states. State-related changes were found in the mean discharge rate of NPBM neurons and in the relationship of their activity to the respiratory cycle. These changes in pneumotaxic center neuronal activity paralleled the variations in respiratory patterns associated with different sleep-waking states. State-related changes in NPBM neuronal activity could partially account for the different respiratory patterns of each sleep-waking state by modulating inspiratory-expiratory phase transitions.

Microelectrophoretic studies with 2-bromo-α-ergocriptine on dopaminergic neurons in the feline caudate nucleus

The influence of microelectrophoretically applied dopamine and pressure released 2-Bromo-α-ergocriptine (CB 154) on the spontaneous activity of single neurones in the feline caudate nucleus was studied. Two types of dopamine sensitive neurones were found: the spike-rate of the first type was reduced by dopamine, the firing of the other type was facilitated by dopamine. Both types of neurones were influenced by pressure released CB 154. Neurones which were excited by dopamine were excited by CB 154, while with the other type CB 154 resulted only in an amplification of the inhibition by dopamine.

The dorsal and medial raphe projections to the substantia nigra in the rat: Electrophysiological, biochemical and behavioural observations

Electrophysiological experiments have been performed in urethane anaesthetized rats to investigate the projections from the dorsal (DRN) and medial raphe nuclei (MRN) to the substantia nigra. The biochemical and behavioural effects following discrete electrolytic lesions in the dorsal and medial raphe have also been investigated. Stimulation of the DRN produced predominantly inhibition of spontaneous activity of single neurones in the substantia nigra though some neurones were also excited. Bilateral stimulation of the substantia nigra produced antidromic spikes in DRN and MRN neurones. Lesions of the DRN and MRN produced a significant reduction in substantia nigra 5-HT concentration. Additionally, DRN lesions reduced striatal 5-HT, while MRN lesions reduced hippocampal 5-HT. Both lesions increased substantia nigra HVA concentration but did not affect DA concentration. Neither DRN nor MRN lesions affected striatal HVA, although DA levels were significantly elevated after 14 days. Animals with DRN lesions explored more than controls or MRN-lesioned animals. However, this behaviour was transient and was not observed after 14 days. On the other hand, MRN-lesioned animals were significantly hyperactive. These observations suggest that the substantia nigra receives a direct monosynaptic inhibitory input from the DRN and MRN and that these pathways use 5-HT as a neurotransmitter serving to tonically inhibit dopaminergic neurones. While 5-HT and dopamine appear to be involved in the control of motor behaviour, the precise relationship between these serotoninergic and dopaminergic systems in this respect is unclear.