Distribution of correlated spiking events in a population-based approach for Integrate-and-Fire networks

Randomly connected populations of spiking neurons display a rich variety of dynamics. However, much of the current modeling and theoretical work has focused on two dynamical extremes: on one hand homogeneous dynamics characterized by weak correlations between neurons, and on the other hand total synchrony characterized by large populations firing in unison. In this paper we address the conceptual issue of how to mathematically characterize the partially synchronous “multiple firing events” (MFEs) which manifest in between these two dynamical extremes. We further develop a geometric method for obtaining the distribution of magnitudes of these MFEs by recasting the cascading firing event process as a first-passage time problem, and deriving an analytical approximation of the first passage time density valid for large neuron populations. Thus, we establish a direct link between the voltage distributions of excitatory and inhibitory neurons and the number of neurons firing in an MFE that can be easily integrated into population–based computational methods, thereby bridging the gap between homogeneous firing regimes and total synchrony.     

The neuronal ensembles of the brain

The conclusion about availability of two types of neuron ensembles in the central nervous structures was made on the basis of proper experimental studies and appropriate literature data analysis. The first is presented by neurons functional cooperation (Hebbian ensembles) formed during learning process on the basis of synchronization by high-frequency oscillator activity. The second is presented by morphological-and-functional structures (Kogan's neuron ensembles) formed during neurogenesis process and genetically destined for biologically valuable patterns recognition. The control of functional state of the brain neuron networks and occurred information processes is realized by non-specific systems either restrict the neurons capability of joining in the rate of global synchronization by synchronization and desynchronization actions or form and maintain the common rhythm of activity in considerable neuron populations. The latter block single elements ability to enter into specific interactions.     

Morphometric comparison between human and rat abducens and oculomotor nerves

A morphologic and morphometric comparison between normal human and rat extraocular muscle nerves was performed using a computer-assisted method to obtain scatter diagrams of relative sheath thickness (g ratio = quotient axon diameter/fiber diameter). Human and rat extraocular muscle nerves (nervus abducens and ramus medialis n. oculomotorii) were excised immediately before the nerve branching at the entering point into the muscle. There was no difference in the absolute number of myelinated fibers between the oculomotor and abducens nerves in both species. The distribution of myelinated fibers was classified according to their g ratios into a two-stage density cluster analysis. Two main populations of nerve fibers for human oculomotor and rat oculomotor and abducens nerves and three main populations for human abducens nerve were differentiated morphometrically and mathematically, differing in their relative sheath thicknesses. There are distinct differences between scatter diagrams of human and rat extraocular muscle nerves, in correlation with the basically different oculomotor functions of these two species. The morphometric differences between human and rat extraocular muscle nerves suggest a difference in the myelination process and the presence of functionally different nerve fibers, strongly indicated by the populations and subpopulations of myelinating nerve fibers peculiar to extraocular muscle. The existence of more than two different types of myelinated fibers in the human nerves implies that the traditional classification based on fiber caliber must be reviewed and a comparison of different classes of nerve and muscle fibers should be performed.     

Reaction of striatal (putamen) neurons on motor and non-motor fragments of behaviour in monkeys

Each putamen neuron responded to several fragments of a behavioural programme, the pattern of such connections being not constant. The response could disappear in a different variant of the behavioural programme while a response to another fragment could occur. Therefore additional variants of the programme were followed by an increase in number of functional modality of a neuron. This was more obvious in motor fragments of the programme. The data obtained suggest that the putamen neurons have no particular specifics, and so involvement of its units in sensory-cognitive processes seem to be more stable than in organisation of movements.     

Differential sensitivity of skeletal and fusimotor neurons to Bcl-2-mediated apoptosis during neuromuscular development

Proper development of the nervous system requires that a carefully controlled balance be maintained between both proliferation and neuronal survival. The process of programmed cell death is believed to play a key role in regulating levels of neuronal survival, in large part through the action of antiapoptotic proteins, such as Bcl-2. Consistent with this, Bcl-2 has been shown to be a key regulator of apoptotic signaling in post-mitotic neurons. However, we still know remarkably little regarding the role that Bcl-2 plays in regulating the survival of specific motor neuron populations. In the present study, we have examined somatic motor neurons of the lumbar spinal cord, and branchiomotor neurons of the facial nucleus in bcl-2-null mice to determine the differential dependence among motor neuron populations with respect to Bcl-2-mediated survival. Examination of neuronal and axon number, axonal area, and the distribution of axonal loss in bcl-2-null mice demonstrates that, in contrast to the great majority of alpha motor neurons, gamma motor neurons exhibit a unique dependence upon bcl-2 for survival. These results demonstrate, for the first time, the connection between Bcl-2 expression, motor neuron survival, and the establishment of different motor populations.     

Gamma oscillations as a mechanism for selective information transmission

In the past decades, many studies have focussed on the relation between the input and output of neurons with the aim to understand information processing by neurons. A particular aspect of neuronal information, which has not received much attention so far, concerns the problem of information transfer when a neuron or a population of neurons receives input from two or more (populations of) neurons, in particular when these (populations of) neurons carry different types of information. The aim of the present study is to investigate the responses of neurons to multiple inputs modulated in the gamma frequency range. By a combination of theoretical approaches and computer simulations, we test the hypothesis that enhanced modulation of synchronized excitatory neuronal activity in the gamma frequency range provides an advantage over a less synchronized input for various types of neurons. The results of this study show that the spike output of various types of neurons [i.e. the leaky integrate and fire neuron, the quadratic integrate and fire neuron and the Hodgkin–Huxley (HH) neuron] and that of excitatory–inhibitory coupled pairs of neurons, like the Pyramidal Interneuronal Network Gamma (PING) model, is highly phase-locked to the larger of two gamma-modulated input signals. This implies that the neuron selectively responds to the input with the larger gamma modulation if the amplitude of the gamma modulation exceeds that of the other signals by a certain amount. In that case, the output of the neuron is entrained by one of multiple inputs and that other inputs are not represented in the output. This mechanism for selective information transmission is enhanced for short membrane time constants of the neuron.     

Reorganization of Composition of Striatal Neurons Correlating with Behavior in the Monkey Macaca nemestrina

The available experimental data do not provide a sufficiently complete picture of the neuronal activity connected with some action of the animal, as they have been obtained under different experimental protocols and as a result of study of different cells. The present work was aimed at studying activity of the same neuron group at different moments of animal's behavior. A monkey (Macaca nemestrina) was taught to perform a behavioral program consisting of several functional heterogeneous actions. The impulsive activity of striatal neurons was recorded in the central region of putamen with coordinates A 16.5, L7, and H 8–10 [18]. The activity of each neuron was recorded during 13 consecutive stages of the same behavioral task. As a whole, in 59 putamen neurons, 767 fragments of neuronal activity were studied. It was shown that the same neurons could be involved at different behavioral stages when the animal performed different actions. At individual stages, the number of neurons common with other behavioral stages reached 70–80% of all reactive cells at the stage. The number of the neurons common within the rest of 12 stages was determined for every program stage. The number of such common neurons established in the experiment was in 142 out of 156 cases higher than their number that could be expected on the basis of statistical relations. The data obtained indicate that the reorganization in composition of behavior-reactive cells at every behavioral stage occurs mainly by using the same neurons but not only the neurons that are specialized for the given action. The polymodality of individual striatal neurons is unlikely to be connected with that they have several functions, but results from that the same neuron can be a constituent of neuronal mosaics of different configurations corresponding to different behavioral moments.     

NPY-mRNA expressions in the nucleus accumbens,caudate putamen and cerebral cortex of apomorphine-susceptible and apomorphine-unsusceptible rats

Using the apomorphine-induced stereotyped gnawing response as a selection criterion, two distinct groups of rats can be distinguished, apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) rats. These two lines differ in several components of both striatal and extrastriatal areas. This study deals with the expression of neuropeptide Y (NPY)mRNA-expressing neurons in the nucleus accumbens, caudate putamen and cerebral cortex of both rat lines, using non-radioactive in situ hybridisation. The morphology of the neurons in the three regions is similar, viz. oblong, rectangular or triangular, with two or three processes. The neurons are homogeneously distributed in all regions, and in the nucleus accumbens they are particularly numerous ventrally to the anterior commissure. Using automated image analysis, the mean numerical density of NPYmRNA-positive neurons per brain region and the mean NPYmRNA expression level per neuron per brain region were determined. No differences appear in the numerical densities of NPYmRNA-containing neurons in the nucleus accumbens, caudate putamen and cortex between APO-SUS and APO-UNSUS rats. However, distinct differences between the rat lines are present in the level of NPYmRNA expression per neuron in the nucleus accumbens and in the caudate putamen, showing that NPY contributes to the differential neurochemical make-up of these rat lines that is responsible for their obvious differences in behaviour, physiology and immune competence.     

What neurons hide behind calretinin immunoreactivity in the human gut?

Calretinin (CALR) is often used as an immunohistochemical marker for the histopathological diagnosis of human intestinal neuropathies. However, little is known about its distribution pattern with respect to specific human enteric neuron types. Prior studies revealed CALR in both myenteric and submucosal neurons, most of which colabel with choline acetyl transferase (ChAT). Here, we specified the chemical code of CALR-positive neurons in small and large intestinal wholemounts in a series of 28 patients. Besides other markers, we evaluated the labeling pattern of CALR in combination with vasoactive intestinal peptide (VIP). In colonic submucosa, CALR and VIP were almost completely colocalized in about three-quarters of all submucosal neurons. In the small intestinal submucosa, both the colocalization rate of CALR and VIP as well as the proportion of these neurons were lower (about one-third). In the myenteric plexus of both small intestine and colon, CALR amounted to 11 and 10 %, respectively, whereas VIP to 5 and 4 % of the whole neuron population, respectively. Colocalization of both markers was found in only 2 and 3 % of myenteric neurons, respectively. In section specimens, nerve fibers coreactive for CALR and VIP were found in the mucosa but not in the muscle coat. Summarizing the present and earlier results, CALR was found in at least one submucosal and two myenteric neuron populations. Submucosal CALR+/VIP+/ChAT± neurons innervate mucosal structures. Furthermore, CALR immunoreactivity in the myenteric plexus was observed in morphological type II (supposed primary afferent) and spiny type I (supposed inter- or motor-) neurons.     

On some properties of stochastic information processes in neurons and neuron populations

The information in the nervous spike trains and its processing by neural units are discussed. In these problems, our attention is focused on the stochastic properties of neurons and neuron populations. There are three subjects in this paper, which are the spontaneous type neuron, the forced type neuron and the reciprocal inhibitory pairs.

1. The spontaneous type neuron produces spikes without excitatory inputs. The mathematical model has the following assumptions. The neuron potential (NP) has the fluctuation and obeys the Ornstein-Uhlenbeck process, because the N P is not so perfectly random as that of the Wiener process but has an attraction to the rest value. The threshold varies exponentially and the NP has the constant lower limit. When the NP reaches the threshold, the neuron fires and the NP is reset to a certain position. After a firing, an absolute refractory period exists. In discussing the stochastic properties of neurons, the transition probability density function and the first passage time density function are the important quantities, which are governed by the Kolmogorov's equations. Although they can be set up easily, we can rarely obtain the analytical solutions in time domain. Moreover, they cover only simple properties. Hence the numerical analysis is performed and a good deal of fair results are obtained and discussed.
2. The forced type neuron has input pulse trains which are assumed to be based on the Poisson process. Other assumptions and methods are almost the same as above except the diffusion approximation of the stochastic process. In this case, we encounter the inhomogeneous process due to the pulse-frequency-modulation, whose first passage time density reveals the multimodal distribution. The numerical analysis is also tried, and the output spike interval density is further discussed in the case of the periodic modulation.
3. Two types of reciprocal inhibitory pairs are discussed. The first type has two excitatory driving inputs which are mutually independent. The second type has one common excitatory input but it advances in two ways, one of which has a time lag. The neuron dynamics is the same as that of the forced type neuron and each neuron has an identical structure. The inputs are assumed to be based on the Poisson process and the inhibition occurs when the companion neuron fires. In this case, the equations of the probability density functions are not obtained. Hence the computer simulation is tried and it is observed that the stochastic rhythm emerges in spite of the temporally homogeneous inputs. Furthermore, the case of inhomogeneous inputs is discussed.

     

Multiple subcellular mRNA distribution patterns in neurons: A nonisotopic in situ hybridization analysis

Previous studies have established that most of the mRNAs that neurons express are localized in the cell body and very proximal dendrites, whereas a small subset of mRNAs is present at relatively high levels in dendrites. It is not clear, however, whether particular mRNAs have the same subcellular distribution in different types of neurons or whether different types of neurons sort mRNAs in different ways. The present study was undertaken to address these questions. Nonisotopic in situ hybridization techniques were used to define the subcellular localization of representative mRNAs including β-tubulin, low-molecular-weight neurofilament protein (NF-68), high-molecular-weight microtubule-associated protein (MAP2), growth-associated protein 43 (F1/GAP43), the alpha subunit of calcium/calmodulin-dependent protein kinase II (αCaMII kinase), and poly(A⁺) mRNA. The mRNAs for β-tubulin, neurofilament 68, and F1/GAP43 were restricted to the region of the cell body and very proximal dendrites in most neurons. In some neuron types, however, labeling for NF-68 extended for considerable distances into dendrites. In some neurons that express MAP2, the mRNA was present at the highest levels in the proximal third to half of the dendritic arbor, whereas in other neurons the highest levels of labeling were in the cell body. In most neurons that express αCaMII kinase, the highest levels of the mRNA were in the cell body, but labeling was also present throughout dendrites. However, in a few types of neurons, αCaMII kinase mRNA was largely restricted to the cell body. The fact that there are no general rules for mRNA localization that apply to all neuron types implies the existence of neuron type-specific mechanisms that regulate mRNA distribution. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 473–493, 1997     

Characteristics of human cortical pyramidal neuron development during the second gestational trimester

Prenatal ontogeny of the human neocortex exhibits specific characteristics that make its organization unique. Therefore, experimental data obtained on animal models cannot be extrapolated to human cortex morphogenesis during the middle and late gestational periods. Characteristics of the development of cortical pyramidal neurons of the human brain were studied in the brains of eight fetuses at gestational ages between 16 and 26 weeks. Immunohistochemical labeling of neurons was performed using antibodies against microtubule associated protein 2 (MAP2), a structural protein of microtubules. Expression of this protein marks the beginning of dendrogenesis. MAP2 is mainly located in the neuron body and dendrites, which allowed the neuron morphotype and location in specific cortical layers to be determined. It was shown that MAP2-immunopositive neurons were identifiable in embryonic cortical layer eV as early as the 18th gestational week. By the 25th gestational week, two populations of pyramidal neurons were discernible in the cortical plate, one of them located in layer eV and the other, in layer eIII, which developed later. Since differentiating neurons are known to be more vulnerable than neuroblasts and mature neurons, these results suggest that critical periods for corticofugal and corticocortical populations of pyramidal cells occur at different stages of the second gestational trimester.     

On the evidence for a 'pure' binocular process in human vision

Wolfe (1986, Psychol. Rev. 93, 269-282) proposed a model of human binocular vision based on the assumption of two functionally distinct classes of binocular neuron. These neurons may be regarded as logical AND and OR gates. In the present paper we assess the evidence relevant to this assumption. We find that while both types of binocular neuron have been described in the cortex of cat and monkey, there is no indication that they form functionally separate populations. Critical analysis of the psychophysical evidence for AND and OR channels in human vision suggests that much of the data presented in favor of an AND channel is subject to alternative interpretations. We conclude that the available data are not consistent with the existence of separate channels as proposed by Wolfe.     

Identification of neuron types in the submucosal ganglia of the mouse ileum

The continuing and even expanding use of genetically modified mice to investigate the normal physiology and development of the enteric nervous system and for the study of pathophysiology in mouse models emphasises the need to identify all the neuron types and their functional roles in mice. An investigation that chemically and morphologically defined all the major neuron types with cell bodies in myenteric ganglia of the mouse small intestine was recently completed. The present study was aimed at the submucosal ganglia, with the purpose of similarly identifying the major neuron types with cell bodies in these ganglia. We found that the submucosal neurons could be divided into three major groups: neurons with vasoactive intestinal peptide (VIP) immunoreactivity (51% of neurons), neurons with choline acetyltransferase (ChAT) immunoreactivity (41% of neurons) and neurons that expressed neither of these markers. Most VIP neurons contained neuropeptide Y (NPY) and about 40% were immunoreactive for tyrosine hydroxylase (TH); 22% of all submucosal neurons were TH/VIP. VIP-immunoreactive nerve terminals in the mucosa were weakly immunoreactive for TH but separate populations of TH- and VIP-immunoreactive axons innervated the arterioles in the submucosa. Of the ChAT neurons, about half were immunoreactive for both somatostatin and calcitonin gene-related peptide (CGRP). Calretinin immunoreactivity occurred in over 90% of neurons, including the VIP neurons. The submucosal ganglia and submucosal arterioles were innervated by sympathetic noradrenergic neurons that were immunoreactive for TH and NPY; no VIP and few calretinin fibres innervated submucosal neurons. We conclude that the submucosal ganglia contain cell bodies of VIP/NPY/TH/calretinin non-cholinergic secretomotor neurons, VIP/NPY/calretinin vasodilator neurons, ChAT/CGRP/somatostatin/calretinin cholinergic secretomotor neurons and small populations of cholinergic and non-cholinergic neurons whose targets have yet to be identified. No evidence for the presence of type-II putative intrinsic primary afferent neurons was found. This work was supported by a grant from the National Health and Medical Research Council of Australia (grant no. 400020) and an Australian Research Council international linkage grant (no. LZ0882269) for collaboration between the Melbourne and Bologna laboratories.     

Pattern of lipofuscin pigmentation in nitrergic and non-nitrergic,neurofilament immunoreactive myenteric neuron types of human small intestine

Lipofuscin, an autofluorescent age pigment, occurs in enteric neurons. Due to its broad excitation and emission spectra, it overlaps with commonly used fluorophores in immunohistochemistry. We investigated the pattern of lipofuscin pigmentation in neurofilament (NF)-reactive nitrergic and non-nitrergic human myenteric neuron types. Subsequently, we tested two methods for reduction of lipofuscin-like autofluorescence. Myenteric plexus/longitudinal muscle wholemounts of small intestines of five patients undergoing surgery for carcinoma (aged between 18 and 69 years) were double stained for NF and neuronal nitric oxide synthase (nNOS). Lipofuscin pigmentation patterns were semiquantitatively evaluated by using confocal laser scanning microscopy with three different excitation wave lengths (one for undisturbed lipofuscin autofluorescence and two for specific labellings). Two pigmentation patterns could be detected in the five NF-reactive neuron types investigated. In nitrergic/spiny as well as in non-nitrergic/stubby neurons, coarse, intensely autofluorescent pigment granules were prominent. In non-nitrergic type II, III and V neurons, a fine granular, diffusely distributed and less intensely autofluorescent pigment was obvious. After incubation of wholemounts in either CuSO₄ or Sudan black B solutions, unspecific autofluorescence could be substantially reduced whereas specific NF and nNOS fluorescence remained largely unaffected. We conclude that NF immunohistochemistry is useful for morphological representation of subpopulations of human myenteric neurons. The lipofuscin pigmentation in human myenteric neurons reveals at least two different patterns which can be related to distinct neuron types. Incubations of multiply stained whole mounts in both CuSO₄ or Sudan black B are suitable methods for reducing autofluorescence thus facilitating discrimination between specific (immunohistochemical) and non-specific (lipofuscin) fluorescence.     

Mucopolysaccharides in the dog spinal cord and dorsal root ganglia. A histochemical study.

A histochemical study of mucopolysaccharides in the dog spinal cord and dorsal root ganglia is reported in this paper. The histochemical techniques used were the following: PAS, colloidal iron, toluidine blue (pH 5.4 and 3.5), thionine (pH 5.4 and 3.5) and alcian blue 8GX (pH 1 and 2.5). Some histological stains were used also. Two types of neurons could be observed in spinal cord sections stained with colloidal iron techniques. In some neuron a border line of mucosubstances could be seen. In the dorsal root ganglia, different patterns of Nissl bodies distribution in neurons were described. This different distribution of Nissl bodies is associated with different metachromatic colorations of neurons. By using the colloidal iron method, two types of neurons were also revealed in the dorsal root ganglia: some neurons are of a yellow, small-sized and star-shaped type and others are of a light green, larger and round-shaped type. Mucosubstances in the endoneurium and perineurium of nerve fibers, in the Ranvier nodules and in the Schmidt-Lantermann incisures were observed. The possibility that the functional rhythm in some cases might be responsible for the difference in coloration between the dorsal root ganglia neurons is suggested.     

Dose-dependent response characteristics of antennal lobe neurons in the male moth Agrotis segetum (Lepidoptera: Noctuidae)

Responses of antennal lobe neurons to different amounts of the female-produced pheromone blend and to its individual components were investigated in Agrotis segetum males using intracellular recording methods. We identified three physiological types of antennal lobe neurons, categorized according to their response thresholds to single pheromone components and to the blend: generalist neurons, component-specific neurons and blend-specific neurons. Response and specificity of antennal lobe neurons were largely dose dependent. In most cases specific responses occurred only at low stimulus amounts, while increasing concentrations often resulted in an increase of the number of pheromone stimuli to which the neuron responded. Dose-response relationships often differed between different stimuli activating a neuron. Accepted: 24 May 1997     

Geographical variation in the cranial and external characters of the little tube-nosed bat,Murina silvatica in the Japanese archipelago

The distribution ofMurina silvatica (Yoshiyuki, 1983) in the Japanese archipelago extends over about 2000 km from north to south. Specimens were obtained from populations in Hokkaido and Yakushima, which are at the northern and southern ends of the range, and from two intermediate locations in Honshu. Measurements of cranial and external morphology were examined for evidence of geographical variation. The results of both multivariate analysis of variance and cluster analysis showed that there was no distinct cline in skull morphology among the Hokkaido, Tohoku and Chubu populations. However, the results of multivariate analysis of variance showed that all measures were significantly greater for the Yakushima population than for the others. Similarly, in a dendrogram of cluster analysis, the Yakushima population formed a cluster that was distinct from the other populations. However, as the difference between the Yakushima population and the other populations was less than the variation found within the Hokkaido, Tohoku and Chubu populations, morphological divergence of the Yakushima population was attributable to intraspecific variation. The island of Yakushima is the most isolated of the four locations and the morphological divergence of this population may be associated with its relative geographic isolation.     

A Complete Developmental Sequence of a Drosophila Neuronal Lineage as Revealed by Twin-Spot MARCM

Drosophila brains contain numerous neurons that form complex circuits. These neurons are derived in stereotyped patterns from a fixed number of progenitors, called neuroblasts, and identifying individual neurons made by a neuroblast facilitates the reconstruction of neural circuits. An improved MARCM (mosaic analysis with a repressible cell marker) technique, called twin-spot MARCM, allows one to label the sister clones derived from a common progenitor simultaneously in different colors. It enables identification of every single neuron in an extended neuronal lineage based on the order of neuron birth. Here we report the first example, to our knowledge, of complete lineage analysis among neurons derived from a common neuroblast that relay olfactory information from the antennal lobe (AL) to higher brain centers. By identifying the sequentially derived neurons, we found that the neuroblast serially makes 40 types of AL projection neurons (PNs). During embryogenesis, one PN with multi-glomerular innervation and 18 uniglomerular PNs targeting 17 glomeruli of the adult AL are born. Many more PNs of 22 additional types, including four types of polyglomerular PNs, derive after the neuroblast resumes dividing in early larvae. Although different offspring are generated in a rather arbitrary sequence, the birth order strictly dictates the fate of each post-mitotic neuron, including the fate of programmed cell death. Notably, the embryonic progenitor has an altered temporal identity following each self-renewing asymmetric cell division. After larval hatching, the same progenitor produces multiple neurons for each cell type, but the number of neurons for each type is tightly regulated. These observations substantiate the origin-dependent specification of neuron types. Sequencing neuronal lineages will not only unravel how a complex brain develops but also permit systematic identification of neuron types for detailed structure and function analysis of the brain.