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Probabilistic computation by neuromine networks.

In this paper, we address the question, can biologically feasible neural nets compute more than can be computed by deterministic polynomial time algorithms? Since we want to maintain a claim of plausibility and reasonableness we restrict ourselves to algorithmically easy to construct nets and we rule out infinite precision in parameters and in any analog parts of the computation. Our approach is to consider the recent advances in randomized algorithms and see if such randomized computations can be described by neural nets. We start with a pair of neurons and show that by connecting them with reciprocal inhibition and some tonic input, then the steady-state will be one neuron ON and one neuron OFF, but which neuron will be ON and which neuron will be OFF will be chosen at random (perhaps, it would be better to say that microscopic noise in the analog computation will be turned into a megascale random bit). We then show that we can build a small network that uses this random bit process to generate repeatedly random bits. This random bit generator can then be connected with a neural net representing the deterministic part of randomized algorithm. We, therefore, demonstrate that these neural nets can carry out probabilistic computation and thus be less limited than classical neural nets.

Algorithms↗

The innervation of the human larynx.

OBJECTIVE: To investigate the gross anatomy of the recurrent and superior laryngeal nerves (RLNs and SLNs) in 10 human larynges. METHODS: Whole larynges were processed to clear all soft tissue while leaving nerves stained. Then the main laryngeal nerves and the muscles they innervate were dissected and analyzed. RESULTS: It was found that in all larynges the RLNs and SLNs are connected by nerve branches other than Galen's anastomosis. The most consistent connection is in the interarytenoid muscle, where RLNs and internal SLNs combine in a neural plexus. A less consistent connection occurs in the piriform fossa, where a continuation of the external SLN passes from the cricothyroid muscle to the thyroarytenoid muscle. CONCLUSION: Based on these findings it is proposed that there are significant neural connections between the RLN and SLN systems. In addition, limited cross-innervation is seen from side to side in the area of the interarytenoid muscle. Other findings concern the innervation patterns within the laryngeal muscles. The posterior cricoarytenoid, cricothyroid, and thyroarytenoid muscles all appear to be composed of separate bellies based on the configuration of their nerve supply. Most notable is the region of the thyroarytenoid muscle at the vocal cord margin that is innervated by a nerve plexus of extreme complexity. The details of the innervation patterns suggest functional differences within and between laryngeal muscles.

Acetates↗

A review of diagnostic and functional imaging in headache.

The neuroimaging of headache patients has revolutionised our understanding of the pathophysiology of primary headaches and provided unique insights into these syndromes. Modern imaging studies point, together with the clinical picture, towards a central triggering cause. The early functional imaging work using positron emission tomography shed light on the genesis of some syndromes, and has recently been refined, implying that the observed activation in migraine (brainstem) and in several trigeminal-autonomic headaches (hypothalamic grey) is involved in the pain process in either a permissive or triggering manner rather than simply as a response to first-division nociception per se. Using the advanced method of voxel-based morphometry, it has been suggested that there is a correlation between the brain area activated specifically in acute cluster headache--the posterior hypothalamic grey matter--and an increase in grey matter in the same region. No structural changes have been found for migraine and medication overuse headache, whereas patients with chronic tension-type headache demonstrated a significant grey matter decrease in regions known to be involved in pain processing. Modern neuroimaging thus clearly suggests that most primary headache syndromes are predominantly driven from the brain, activating the trigeminovascular reflex and needing therapeutics that act on both sides: centrally and peripherally.

Brain↗

The use of networks of dissociated rat dorsal root ganglion neurons to induce myelination by oligodencrocytes in culture.

A neuronal culture system has been developed that has the demonstrated ability to induce myelin formation by added oligodendrocytes. Networks of dissociated dorsal root ganglion neurons were prepared by suppressing non-neuronal cells (i.e. fibroblasts and Schwann cells) with a continuous 2 week exposure to 10(-5)M fluorodeoxyuridine in the culture medium. After drug withdrawal, neuroglial cells were introduced in optic nerve implants from 1-2 week-old rats. These added glial cells migrated extensively over the unensheathed neurites and central myelin was formed by 2 weeks after the implant addition.

Animals↗

Neuropeptides in the human dorsal vagal complex: an immunohistochemical study.

The distribution of twelve biologically active neuropeptides, i.e., thyrotropin-releasing hormone, corticotropin-releasing factor, pro-opiomelanocortin-derived peptides (adrenocorticotropic hormone, beta-endorphin, alpha-melanocyte-stimulating hormone), leucine-enkephalin, dynorphin A, dynorphin B, cholecystokinin, substance P, galanin and calcitonin gene-related peptide, was examined by immunohistochemistry in the human dorsal vagal complex including the nucleus of the solitary tract, the dorsal motor nucleus of the vagus and the area postrema. Immunoreactivity of all the twelve neuropeptides was found widely distributed in the various subdivisions of the nucleus of the solitary tract, showing a unique distribution for every peptide. Neuronal cell bodies immunostained with leucine-enkephalin, galanin and dynorphin B were found in this region. There were no immunopositive perikarya for any of the peptides in the other structures studied. Fibers containing galanin, corticotropin-releasing factor, substance P, dynorphin B, thyrotropin-releasing hormone and calcitonin gene-related peptide were observed at a relatively high density in the nucleus of the solitary tract. In the same structure, a moderately dense network of fibers immunostained with dynorphin A, cholecystokinin and leucine-enkephalin, but only solitary pro-opiomelanocortin-derived peptides-containing fiber fragments were observed. In the dorsal motor nucleus of the vagus the most prominent network of fibers was found to contain thyrotropin-releasing hormone, galanin and substance P. In contrast to these, no beta-endorphin immunoreactivity was detected. The area postrema contained only moderate to low densities of galanin-, substance P-, calcitonin gene-related peptide-, dynorphin B- and cholecystokinin-immunoreactive fibers.

Adult↗

Cellular localization of Shab and Shaw potassium channels in the lobster stomatogastric ganglion.

The motor pattern generated by the 14 neurons composing the pyloric circuit in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, is organized not only by the synaptic connections between neurons, but also by the characteristic intrinsic electrophysiological properties of the individual cells. These cellular properties result from the unique complement of ion channels that each cell expresses, and the distribution of those channels in the cell membranes. We have mapped the STG expression of shab and shaw, two genes in the Shaker superfamily of potassium channel genes that encode voltage-dependent, non-inactivating channels. Using antibodies developed against peptide sequences from the two channel proteins, we explored the localization and cell-specific expression of the channels. Anti-Shab and anti-Shaw antibodies both stain all the pyloric neurons in the somata, as well as their primary neurites and branch points of large neurites, but to varying degrees between cell types. Staining was weak and irregular (Shaw) or absent (Shab) in the fine neuropil of pyloric neurons, where most synaptic interactions occur. There is a high degree of variability in the staining intensity among neurons of a single cell class. This supports Golowasch et al.'s [J Neurosci 19 (1999) RC33; Neural Comput 11 (1999) 1079] hypothesis that individual cells can have similar firing properties with varying compositions of ionic currents. Both antibodies stain the axons of the peripheral nerves as they enter foregut muscles. We conclude that both Shab and Shaw channels are appropriately localized to contribute to the noninactivating potassium current in the stomatogastric nervous system.

Analysis of Variance↗

Stimulus time-locked responses of motoneurons during forelimb fictive locomotion evoked by repetitive stimulation of the lateral funiculus.

In cat forelimb fictive locomotion evoked by repetitive stimulation of the upper cervical lateral funiculus, locomotor discharges consisted of activities time-locked to each stimulus, which were rhythmically modulated. The stimulus time-locked activities were investigated by intracellular recording from motoneurons. In both elbow flexor and extensor motoneurons, there observed stimulus time-locked disynaptic EPSPs, trisynaptic IPSPs and polysynaptic EPSPs, all of which were rhythmically modulated with specific patterns. The disynaptic EPSPs of flexor motoneurons were facilitated in the flexor phase of locomotion, whereas those of extensor motoneurons were facilitated from the flexor phase to the flexor-to-extensor transition phase. Modulation depth was larger in flexor motoneurons. Trisynaptic IPSPs changed in amplitude in parallel with the disynaptic EPSPs of the antagonistic motoneurons. Late, polysynaptic EPSPs of both flexor and extensor motoneurons increased in amplitude along with corresponding nerve discharges. After lesions of the lateral funiculus at C6/C7, both the disynaptic EPSPs and trisynaptic IPSPs were abolished in the motoneurons located caudally to the lesions. However, only trisynaptic IPSPs were lost in the rostrally located motoneurons. Furthermore, the lesions disclosed that extensor motoneurons received another kind of stimulus time-locked EPSPs, trisynaptic EPSPs, which were transmitted through the ventral part of the spinal cord, and rhythmically facilitated in the extensor phase. Stimulus time-locked PSPs observed in this study may at least in part be evoked by last-order interneurons of the central pattern generator, which may be reciprocally organized.

Action Potentials↗

The ventral medullary respiratory network of the mature mouse studied in a working heart-brainstem preparation.

1. This report provides the first description of respiratory network activity within the ventrolateral medulla of the mature mouse obtained from a unique working heart-brainstem preparation (WHBP). 2. In the WHBP three distinct respiratory phases were evident in recordings of both phrenic and vagal efferent nerves. These included a ramp inspiratory (I) discharge, post-inspiratory (PI) activity and a silent or expiratory interval (E2). 3. Extracellular recordings were made from different types of respiratory neurones located within, or in close proximity to, the nucleus ambiguus. Based on firing patterns and phase relative to phrenic nerve discharge, respiratory neurone types, including pre-inspiratory (PreI), early-inspiratory, throughout inspiratory (I), late-inspiratory, post-inspiratory (PI) and stage II expiratory or E2 neurones were characterized. 4. Intracellular recordings were made from four types of respiratory neurones (PreI, I, PI and E2 neurones). PreI neurones were depolarized maximally during the E2-inspiratory transition. I neurones exhibited a ramp depolarization which started either before or at the onset of phrenic discharge. Based on the kinetics of the inspiratory-related hyperpolarizations and duration of discharge, two types of PI neurones were found (rapidly adapting and slowly adapting). E2 neurones were hyperpolarized during both the inspiratory and post-inspiratory phases. 5. Phase-dependent chloride-mediated inhibition was studied in PreI, PI and E2 neurones and included: late inspiratory inhibition of PreI neurones; inspiratory-related inhibition of PI and E2 neurones; and post-inspiratory inhibition of PreI and E2 neurones. In addition, pre-inspiratory inhibition of PI neurones was also demonstrated. 6. The WHBP appears to be viable for analysing reflex, synaptic and cellular mechanisms regulating respiratory activity in an in vitro milieu. The synaptic organization of the respiratory network of the mouse appears comparable to that of the rat and cat. The possibility of a mutual inhibitory interaction between PreI and PI neurones is discussed in terms of the functional organization of the respiratory network in the mouse.

Animals↗

Dissection of the neuron network in the catfish inner retina. II. Interactions between ganglion cells.

1. To characterize signal interactions between ganglion cells, extrinsic current, either sinusoidally or white-noise modulated, was injected into a ganglion cell and the resulting extracellular spike discharges were recorded from a neighboring ganglion cell. 2. Current injected into an ON-ganglion (GA) cell modulated the spike discharges of a neighboring ON-ganglion cell (GA). Similarly, a current injected into an OFF-ganglion (GB) cell modulated the spike discharges of a neighboring OFF-ganglion (GB) cell. The signal transmission between ganglion cells of the same response polarity was fast and sign-noninverting. The transfer function was lowpass with a cutoff frequency of 30 Hz. The efficacy of the transmission was comparable to that from bipolar or amacrine to ganglion cells of the same polarity. 3. Current injected into an ON-ganglion (GA) cell modulated the spike discharges of a neighboring OFF-ganglion (GB) cell; the signal transmission was slow and sign-noninverting. Correspondingly, current injected into an OFF-ganglion (GB) cell modulated the spike discharges of a neighboring ON-ganglion (GA) cell; transmission was slow and sign-inverting. 4. A brief electrical stimulation of the optic nerve activated a single antidromic ganglion cell spike at threshold. With suprathreshold stimulation, multiple spikes appeared, which probably were activated orthodromically. Changes in membrane potential of ganglion and amacrine cells induced by optic nerve stimulation usually lasted 50-80 ms, with an initial depolarization followed by hyperpolarization. We interpret such long-lasting responses to be mediated by reciprocal circuits that include amacrine, bipolar, and ganglion cells. 5. Together with the observations made by Sakai and Naka, we conclude that virtually almost all amacrine, bipolar, and ganglion cells are functionally interconnected; direct and fast connections are established among ON-cells and similarly among OFF-cells, and complex, indirect connections are established between ON- and OFF-cells.

Animals↗

Neuronal circuits associated with the output of the dorsal cochlear nucleus through fusiform cells.

1. Intracellular recordings were made from 21 anatomically identified fusiform cells in the dorsal cochlear nucleus (DCN) of mice in slices. The aim of the experiments was to dissect the synaptic responses to shocks of the auditory nerve to correlate functional characteristics with the different classes of synaptic inputs. 2. When depolarized from rest (-57 +/- 5 mV) with current pulses, fusiform cells fired regular, overshooting action potentials that were followed by two undershoots. The frequency of firing increased with the strength of injected current by between 100 and 300 spikes/s/nA. The current-voltage relationship rectified between 10 and 15 mV below the resting potential. The slopes of current-voltage relationships of fusiform cells in the range between the resting potential and 10 mV hyperpolarization indicated an average input resistance of 86 +/- 37 M omega. 3. In each of the labeled fusiform cells frequent, spontaneous inhibitory postsynaptic potentials (IPSPs) were recorded singly or in bursts. Some, but not all, IPSPs were preceded by a slowly rising excitatory postsynaptic potential (EPSP). The temporal association of spontaneous EPSPs and IPSPs suggests that they are driven by a common source, possibly granule cells. 4. Shocks to the auditory nerve evoked synaptic responses consisting of early (1 to approximately 10 ms) and late (approximately 10 to 100 ms) components. 6,7-Dinitroquinoxaline-2,3-dione (DNQX) at 20 to 40 microM eliminated all detectable excitation and all late IPSPs. Late bursts of IPSPs, therefore, are mediated through a polysynaptic pathway that includes a DNQX-sensitive stage. Strong shocks to the nerve root elicited single monosynaptic IPSPs, indicating that inhibitory interneurons have processes close to the auditory nerve. Strychnine at 0.5 microM eliminated all detectable inhibition. 6. Cuts through the posteroventral cochlear nucleus (PVCN), which severed the descending branches of auditory nerve fibers, eliminated early EPSPs and IPSPs leaving late, slowly rising EPSPs and bursts of IPSPs in responses to shocks of the auditory nerve. Late, slowly rising EPSPs and bursts of IPSPs, as well as monosynaptic IPSPs, could also be evoked by stimulating the anteroventral cochlear nucleus (AVCN). 7. Focal applications of glutamate evoked excitation and inhibition from many parts of a slice, with patterns varying among cells, indicating that fusiform cells receive inputs through several groups of interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Intersegmental and local interneurons in the metathorax of the stick insect Carausius morosus that monitor middle leg position.

1. In the stick insect, proprioceptive information from the middle leg is used to define the target for the swing movement of the adjacent rear leg ("targeting behavior"). To investigate the underlying neural circuits, intracellular recordings were made in the ganglion controlling the rear leg, the metathoracic ganglion, while systematically moving the tarsus of the middle leg. 2. Several intersegmental interneurons and one local interneuron were identified as possible contributors to the targeting behavior. The intersegmental interneurons code the position of the middle leg tarsus in a highly simplified manner: test movements of the middle leg in the dorsal, lateral, and caudal directions from the standard starting position at right angles to the thorax elicit phasic-tonic responses in three different intersegmental neurons. The response in each interneuron actually reflects the movement and position at only one joint of the middle leg: for the neurons responding primarily to movement in the caudal, dorsal, and lateral test directions, the adequate stimulus is movement at the subcoxal joint, the coxa-trochanter joint, and the femur-tibia joint, respectively. 3. The metathoracic local interneuron integrates information from ipsilateral middle and rear legs in such a way as to provide an approximate measure of the distance between the two tarsi in the longitudinal direction. It is depolarized in a phasic-tonic manner both by caudal movements of the ipsilateral middle leg and by rostral movements of the ipsilateral rear leg. The adequate stimulus in each case is the change in the angle at the subcoxal joint of the leg moved. Depolarization of this neuron activates retractor motoneurons, which is consistent with a role in terminating the swing movement. 4. Altogether the results indicate first, that the targeting behavior could be controlled by very few intersegmental channels and, second, that the nervous system encodes the position of the middle leg tarsus in terms of joint angles rather than in abstract, body-centered coordinates.

Animals↗

Expression of nerve growth factor, p75, and trk in the somatosensory and motor cortices of mature rats: evidence for local trophic support circuits.

Neurotrophins such as nerve growth factor (NGF) are critical for the maintenance of CNS neurons. We determined the expression of NGF and the neurotrophin receptors p75 and trk in the somatosensory and motor cortices of mature rats with immunohistochemical techniques. Sections of mature rat cortex were processed immunohistochemically with primary antibodies directed against NGF, p75, or trk. The distribution of immunoreactive elements was examined, and stereological techniques were used to determine the density and size of immunoreactive cell bodies. Some sections processed for trk immunoreactivity were examined with an electron microscope. From the size and morphology of the labeled cells, it appeared that only neurons in the gray matter were NGF-positive. NGF was detected in one-third of the neurons in layers II-III, V, and VI of both somatosensory cortex and motor cortex; however, fewer than 1 in 12 of the layer IV neurons was NGF-positive. With the notable exception of layer V, few cell bodies (2-10% of the total population) were p75- or trk-immunoreactive. Layer Vb was replete with receptor-positive cell bodies; more than one-third of the layer Vb neurons were p75- or trk-positive. All labeled cells appeared to be pyramidal neurons. The distribution of p75 labeling with the two anti-p75 antibodies was indistinguishable. In addition, the neuropil in the supragranular laminae was p75- or trk-positive. Electron microscopy showed that trk immunoreactivity was also expressed by dendrites. Only rarely were immunoreactive axons detected. In summary, NGF is expressed by cortical neurons throughout cortex, and neurotrophin receptors are widely produced by postsynaptic targets. Thus, NGF appears to participate in an intracortical autoregulatory system. The strong expression of neurotrophin receptors by pyramidal neurons in layer Vb (the origin of brainstem and spinal cord projections) suggests that the neurotrophins are especially critical for the regulation of corticofugal projection systems.

Animals↗

Diagnosis and therapy of ultrashort Hirschsprung's disease.

BACKGROUND: Although ultrashort Hirschsprung's disease (UHD) was enzyme-histochemically characterised about 35 years ago, its existence is still often ignored. The aim of this study is to summarise the clinical diagnostic, incidence, gender ratio, morphological characteristics, and therapy over 15 years. METHODOLOGY: The reliable diagnosis of suspected UHD requires a minimal enema of contrast medium to exclude Hirschsprung's disease (HD). In UHD during pressing or crying no reflux of contrast medium is observed. Final proof of UHD is an enzyme-histochemical biopsy examination of distal rectal mucosa. The biopsies must demonstrate submucosa and be taken from the dentate line and 1 cm, 2 cm, 4 cm and 6 cm above the dentate line. The cryostat sections must be cut 15 microm thick; this thickness is reduced to 4.5 microm by the thawing, spreading and drying of the sections on microscope slides. A reliable diagnosis of UHD needs an enzyme-histochemical acetylcholinesterase reaction of native sections of rectal mucosa. RESULTS: UHD develops with first symptoms of chronic constipation in the second half of the first year of life. The chronic constipation proves to be therapy resistant. In HD constipation occurs in the first weeks of life or after weaning. In contrast to HD, no nerve fibres with increased AChE activity are observed in the lamina propria mucosa. Nets of nerve fibres with increased AChE activity can be found only in the muscularis mucosa and the musculus corrugator cutis ani (MCCA). The therapy of choice has proven to be a partial myectomy of the distal internal sphincter if dilatation of the internal sphincter was ineffective. UHD is either limited to the anal ring, or extends 3 - 4 cm into the distal rectum. Over the past 15 years, UHD had in our series an incidence of 13.4 % of all aganglionoses. The gender ratio of girls to boys was 1 : 2. CONCLUSION: UHD is reliably diagnosed by an AChE reaction in native biopsy sections from the anocutaneous transitional zone and, potentially, from 3 - 4 cm above the pectinate line. As UHD is always accompanied by aganglionosis of the distal internal sphincter, an increase in AChE activity is observed in the nerve fibres of the MCCA. The therapy of choice is a partial myectomy of the distal internal sphincter.

Acetylcholinesterase↗