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[Treatment of severe hearing loss. Hopeful results with cochlear implants and nerve cell implantations].

Progress in techniques and strategies for tissue engineering has increased our interest in allografting and xenografting in various organ systems. Previous work has shown that peripherally implanted fetal dorsal root ganglion neurons (DRGs) can grow axons across the boundary between the central and peripheral nervous system in the dorsal root and make functional connections within the spinal cord. We have extended this experimental paradigm to the auditory system and successfully implanted fetal DRG neurons into the normal and deafened cochlea, adjacent to deafferented auditory spiral ganglion neurons. These findings demonstrate the feasibility of using fetal sensory cells in a new strategy to repair or replace the auditory nerve. Further studies will show whether the surviving DRGs can restore a functional conduit from the cochlea to the brainstem. If so, implanting neuronal tissue close to the auditory nerve could be used to regain auditory function in e.g. profoundly deaf patients.

Animals↗

Olfactory impairments in patients with unilateral cerebellar lesions are selective to inputs from the contralesional nostril.

Functional imaging studies of olfaction have consistently reported odorant-induced activation of the cerebellum. However, the cerebellar role in olfaction remains unknown. We examined the olfactory and olfactomotor abilities of patients with unilateral cerebellar lesions, comparing performance within subjects across nostrils, as well as between subjects with age-matched and young controls. Regarding olfactory performance, initial testing revealed that patients had a contralesional impairment in olfactory identification but not olfactory detection threshold. However, when tested under conditions that prevented compensatory sniffing strategies, the patients also exhibited a contralesional olfactory detection impairment. Regarding olfactomotor function, a healthy olfactomotor system generates sniffs that are (1) sufficiently vigorous and (2) inversely proportional to odorant concentration in sniff mean airflow velocity, maximum airflow velocity, volume, and duration. Patients' sniffs were lower in overall airflow velocity and volume in comparison with control participants. Furthermore, reduced sniff velocity predicted poorer detection thresholds in patients. Finally, whereas young controls used concentration-dependent sniffs, there was a trend in that direction only for age-matched controls. Patients used sniffs that were concentration invariant. In conclusion, cerebellar lesions impacted olfactory and olfactomotor performance. These findings strongly implicate an olfactocerebellar pathway prominent in odor identification and detection that functionally connects each nostril primarily to the contralateral cerebellum.

Acoustic Stimulation↗

Homeobox gene expression in adult dorsal root ganglia during sciatic nerve regeneration: is regeneration a recapitulation of development?

After damage of the sciatic nerve, a regeneration process is initiated. Neurons in the dorsal root ganglion regrow their axons and functional connections. The molecular mechanisms of this neuronal regenerative process have remained elusive, but a relationship with developmental processes has been conceived. This chapter discusses the applicability of the developmental hypothesis of regeneration to the dorsal root ganglion; this hypothesis states that regeneration of dorsal root ganglion neurons is a recapitulation of development. We present data on changes in gene expression upon sciatic nerve damage, and the expression and function of homeobox genes. This class of transcription factors plays a role in neuronal development. Based on these data, it is concluded that the hypothesis does not hold for dorsal root ganglion neurons, and that regeneration-specific mechanisms exist. Cytokines and the associated Jak/STAT (janus kinase/signal transducer and activator of transcription) signal transduction pathway emerge as constituents of a regeneration-specific mechanism. This mechanism may be the basis of pharmacological strategies to stimulate regeneration.

Animals↗

The connecting tubule: a functional subdivision of the rabbit distal nephron segments.

Studies on adenylate cyclase response of the nephron fragments to hormones and drugs have suggested that there is a functionally distinct segment tentatively called the connecting tubule (CNT), which is located between the distal (DT) and the cortical collecting tubule (CCT). The functional significance of these biochemical findings was examined with isolated rabbit renal tubules perfused in vitro. The transepithelial voltage (PDt) of the DT, CNT, and CCT were, respectively, -28.7 +/- 3.24 mV (24), -27.0 +/- 2.69 mV (24), and -3.5 +/- 2.14 mV (11) in the normal rabbits. The PDt of the CCT increased to -32.2 +/- 2.02 mV (33) when rabbits were pretreated for at least 3 days with deoxycorticosterone acetate, DOCA (1 mg/kg/day, i.m.), whereas the PDt of the DT and the CNT remained unchanged. The PDt of the CCT obtained from deoxycorticosterone acetate- (DOCA) treated animals decreased after addition of antidiuretic hormone (ADH) or isoproterenol (ISO) to the bath. The PDt of the CNT also responded to these agents, but the dose required to obtain the same response was quite different: The CNT was 100-fold more sensitive to ISO as compared to the CCT, whereas the CCT was 10-fold more sensitive to ADH than was the CNT. In contrast, the PDt of the DT did not respond to any of these agents, even at a higher concentration. After addition of ADH (200 microU/ml) to the bath, the osmotic water permeability (10(-8) cm2 . sec-1 . atm-1) of the CCT increased from 1.13 +/- 0.83 to 7.46 +/- 2.36, but that of the CNT remained low (0.36 +/- 0.78 in control vs. 0.48 + 0.64 after ADH). These observations support the view that the CNT is functionally distinct from either the DT or the CCT.

Animals↗

Mixed H2/H infinity design for a decentralized discrete variable structure control with application to mobile robots.

In this paper, a decentralized discrete variable structure control via mixed H2/H infinity design was developed. In the beginning, the H2-norm of output error and weighted control input was minimized to obtain a control such that smaller energy consumption with bounded tracking error was assured. In addition, a suitable selection of this weighted function (connected with frequency) could reduce the effect of disturbance on the control input. However, an output disturbance caused by the interactions among subsystems, modeling error, and external load deteriorated system performance or even brought about instability. In this situation, the H infinity-norm of weighted sensitivity between output disturbance and output error was minimized to attenuate the effect of output disturbance. Moreover, an appropriate selection of this weighted function (related to frequency) could reject the corresponding output disturbance. No solution of Diophantine equation was required; the computational advantage was especially dominated for low-order system. For further improving system performance, a switching control for every subsystem was designed. The proposed control (mixed H2/H infinity DDVSC) was a three-step design method. The stability of the overall system was verified by Lyapunov stability criterion. The simulations and experiments of mobile robot were carried out to evaluate the usefulness of the proposed method.

Algorithms↗

[Spectral power and cortical interactions in the beta2 rhythm in normal subjects and schizophrenic patients].

Spectral and coherence characteristics of the beta 2 rhythm (20-40 Hz) were compared in patients with acute schizophrenia (the first episode), patients with chronic schizophrenia (disease duration more than two years), and healthy subjects (control group) during cognitive task performance. Examination showed the "excessive" spectral power of this rhythm in the prefrontal cortical areas in patients with acute schizophrenia and its "insufficient" spectral power in all derivations of the right hemisphere in patients with the chronic form as compared to the controls. The similarity of the beta 2 spectral power distribution in different cortical areas measured by covariance method decreased with increase in psychopathologic manifestations. Coherent analysis revealed a substantially lower number of cortico-cortical functional connections in schizophrenic patients than in healthy subjects, absence of interhemispheric connections in patients with acute schizophrenia, and a slight increase in their number if patients with the chronic disease. However, as distinct from the controls revealing many inter- and intrahemispheric connections in all cortical areas, in schizophrenics the interhemispheric connections were observed only in the posterior cortical regions. The results point to a disorder of interhemispheric interaction in schizophrenia.

Adolescent↗

Gut thoughts on the Golgi complex.

The new millennium coincides within 1 year of Camillo Golgi's centennial celebrations. It is quite remarkable that the structure and formation of this organelle is as controversial today as was its mere existence from Golgi's time to the 1950s, when EM approaches were introduced. Since the late 1950s, two opposing models of Golgi structure and function have split the Golgi scientific community, namely vesicular transport versus organelle maturation. Although a few years ago Golgi maturation seemed to be 'out for the count', it has recently seen an almost messianic revival. In this review, I argue that this large-scale desertion from the vesicle transport model to the maturation camp is premature. I propose an alternative, dynamic steady-state model, in which transient tubular connections function in parallel to vesicular transport and that the biosynthetic pathway is made up of three major distinct compartments: the ER, the Golgi and the TGN.

Animals↗

Tuning and playing a motor rhythm: how metabotropic glutamate receptors orchestrate generation of motor patterns in the mammalian central nervous system.

Repeated motor activities like locomotion, mastication and respiration need rhythmic discharges of functionally connected neurons termed central pattern generators (CPGs) that cyclically activate motoneurons even in the absence of descending commands from higher centres. For motor pattern generation, CPGs require integration of multiple processes including activation of ion channels and transmitter receptors at strategic locations within motor networks. One emerging mechanism is activation of glutamate metabotropic receptors (mGluRs) belonging to group I, while group II and III mGluRs appear to play an inhibitory function on sensory inputs. Group I mGluRs generate neuronal membrane depolarization with input resistance increase and rapid fluctuations in intracellular Ca(2+), leading to enhanced excitability and rhythmicity. While synchronicity is probably due to modulation of inhibitory synaptic transmission, these oscillations occurring in coincidence with strong afferent stimuli or application of excitatory agents can trigger locomotor-like patterns. Hence, mGluR-sensitive spinal oscillators play a role in accessory networks for locomotor CPG activation. In brainstem networks supplying tongue muscle motoneurons, group I receptors facilitate excitatory synaptic inputs and evoke synchronous oscillations which stabilize motoneuron firing at regular, low frequency necessary for rhythmic tongue contractions. In this case, synchronicity depends on the strong electrical coupling amongst motoneurons rather than inhibitory transmission, while cyclic activation of K(ATP) conductances sets its periodicity. Activation of mGluRs is therefore a powerful strategy to trigger and recruit patterned discharges of motoneurons.

Action Potentials↗

[Functional magnetic resonance in the evaluation of the activity of the anterior cingulate cortex using Stroop's paradigm].

INTRODUCTION: Stroop s paradigm has been used to evaluate the anterior attention system which regulates the inhibitory capacity of automatic responses. Functional neuroimaging techniques have shown a preponderant role for the anterior cingulate cortex in carrying out this paradigm. OBJECTIVE: To evaluate the activity of the anterior cingulate cortex in view of its clinical importance in the study of neurological and psychiatric disorders. PATIENTS AND METHODS: Eleven healthy volunteers took part in the study. The functional images were analyzed using the software SPM99 and by second order individual and group analysis. RESULTS: Initial local analysis showed activation in the right anterior cingulated cortex (Brodmann s area 32) and left central (areas 31 and 23); caudate nucleus (right body and left tail) and thalamus (bilateral). Overall there was significant activation of the left hemisphere, in areas 44 (Broca s area), 7, 40 (supra marginal gyrus and insular cortex, and in the right hemisphere in area 19. In spite of this there was great individual variation. CONCLUSIONS: The overall results are concordant with complex functional connections for attention and the control of automatic responses. In our study the anterior cingulated cortex was not selectively activated. The activation of the thalamus and caudate nucleus may be explained by their involvement in the frontostriatal circuits. The lack of individual consistency may be due to different personal cognitive styles of resolving conflicts. According to our results, Stroop s paradigm would not be clinically useful for showing good or bad functioning of the anterior cingulated cortex.

Adolescent↗

Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.

CONTEXT: Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. OBJECTIVE: To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Fifteen adolescents with generalized anxiety disorder and 20 controls. MAIN OUTCOME MEASURES: Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention. RESULTS: While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P<.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex. CONCLUSIONS: This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.

Adolescent↗

Postembryonic development of the dorsal ocellus of the American cockroach.

Postembryonic development of the dorsal ocellus of the cockroach Periplaneta americana was examined. Small ocelli (20 micron in diameter) with less than 100 cells in the newly hatched nymph become adult ocelli (more than 500 micron in diameter) with more than 10,000 retinular cells, through ten to 11 nymphal stages. Thus, sequential steps of morphogenesis of rhabdomeres from loose interdigitations of apposed cell membranes to regularly arranged microvilli can be seen in the nymphal ocelli. Some retinular axons appear to extend into the brain as a bundle in the first-instar nymph. Retinular axons differentiated later also extend toward the brain, but there is no evidence that they enter it. The ultrastructure of the ocellus and component analysis of the ocellar electroretinogram suggest that functional connections between retinular axons and ocellar interneurons do not occur in the ocellar capsule until mid (the fifth or sixth)-instar nymphs. The ocellar diameter increases linearly with increase in body length during the nymphal stages, but it increases by a factor of 1.5-2.0 during the final molting: the body length of the adult is almost the same as that of the last-instar nymph. These data suggest that the function of the dorsal ocelli may be closely related to specific adult behavior such as flight.

Animals↗

Development and maintenance of a simple reflex circuit in small-patch mosaics of Drosophila: effects of altered neuronal function and developmental arrest.

A combined genetic, anatomical, and behavioral approach has been undertaken to study the developmental and functional plasticity of identified bristle mechanosensory neurons in Drosophila. A stereotyped grooming reflex in decapitated flies enabled simple but reliable assessments of the functional output of individual bristle sensory cells to correlate with their axonal projections and terminal arbors revealed by the cobalt backfill technique. Construction of small-patch mosaics that contain only a single mutant bristle allowed functional perturbation of individual neurons within an otherwise normal environment. Mutations that affect nerve excitability and membrane recycling have been used to examine their effects on neuronal pathfinding, arborization, and the initiation and maintenance of functional connections. Previous studies (Burg and Wu, 1986, J. Neurosci. 6:2968-2976; 1989, Dev. Biol. 131:505-514) have demonstrated that para(ts)nap(ts) double-mutant sensory neurons, in which action potentials are unconditionally blocked by defects in sodium currents, and eag Sh double-mutant sensory cells, in which membrane excitability is increased by alterations in potassium currents, can establish and maintain central projections that are indistinguishable from their functionally normal counterparts. Mutations of the shi(ts) gene cause a temperature-sensitive, reversible block of the membrane recycling process, resulting in arrest of neuronal growth in culture (Kim and Wu, 1987, J. Neurosci. 7:3245-3255) and depletion of synaptic vesicles that leads to transmission blockade at established synapses (Ikeda, Ozawa, and Hagiwara, 1976, Nature 259:489-491; Koenig and Ikeda, 1983, J. Neurobiol. 14:411-419; 1989, J. Neurosci. 9:3844-3860). Prolonged heat treatments (up to 16% of total development time) of small-patch shi(ts) mosaics at different pupal stages did not prevent the establishment of central projections characteristic of the various sensory cell types. However, none of the shi(ts) sensory neurons heat-pulsed during the initial or the final 16% of pupal development were able to initiate the reflex behavior, although a proportion of those treated in other periods apparently established functional contacts with appropriate targets to support the characteristic cleaning reflex. The possibility exists that the membrane recycling process blocked in shi(ts) cells provides a crucial mechanism for cell-cell interactions taking place during initial differentiation and final synaptic stabilization, and possibly competition, in the developing sensory neuron. Heat treatments of adult shi(ts) mosaics blocked the reflex initiated by the mutant (but not the surrounding normal) bristles, as expected from the effect of synaptic block.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Absence of lutein, violaxanthin and neoxanthin affects the functional chlorophyll antenna size of photosystem-II but not that of photosystem-I in the green alga Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii double mutant npq2 lor1 lacks the beta, epsilon-carotenoids lutein and loroxanthin as well as all beta,beta-epoxycarotenoids derived from zeaxanthin (e.g. violaxanthin and neoxanthin). Thus, the only carotenoids present in the thylakoid membranes of the npq2 lor1 cells are beta-carotene and zeaxanthin. The effect of these mutations on the photochemical apparatus assembly and function was investigated. In cells of the mutant strain, the content of photosystem-II (PSII) and photosystem-I (PSI) was similar to that of the wild type, but npq2 lor1 had a significantly smaller PSII light-harvesting Chl antenna size. In contrast, the Chl antenna size of PSI was not truncated in the mutant. SDS-PAGE and Western blot analysis qualitatively revealed the presence of all LHCII and LHCI apoproteins in the thylakoid membrane of the mutant. The results showed that some of the LHCII and most of the LHCI were assembled and functionally connected with PSII and PSI, respectively. Photon conversion efficiency measurements, based on the initial slope of the light-saturation curve of photosynthesis and on the yield of Chl a fluorescence in vivo, showed similar efficiencies. However, a significantly greater light intensity was required for the saturation of photosynthesis in the mutant than in the wild type. It is concluded that zeaxanthin can successfully replace lutein and violaxanthin in most of the functional light-harvesting antenna of the npq2 lor1 mutant.

Animals↗

Developmental changes in the neurotransmitter regulation of correlated spontaneous retinal activity.

Synchronized spontaneous rhythmic activity is a feature common to many parts of the developing nervous system. In the early visual system, before vision, developing circuits in the retina generate synchronized patterns of bursting activity that contain information useful for patterning connections between retinal ganglion cells and their central targets. However, how developing retinal circuits generate and regulate these spontaneous activity patterns is still incompletely understood. Here we show that in developing retinal circuits, the nature of excitatory neurotransmission driving correlated bursting activity in ganglion cells is not fixed but undergoes a developmental shift from cholinergic to glutamatergic transmission. In addition, we show that this shift occurs as presynaptic glutamatergic bipolar cells form functional connections onto the ganglion cells, implicating the role of bipolar cells in providing endogenous drive to bursting activity later in development. This transition coincides with the period when subsets of ganglion cells (On and Off cells) develop distinct activity patterns that are thought to underlie the refinement of their connectivity with their central targets. Here, our results suggest that the differences in activity patterns of On and Off ganglion cells may be conferred by differential synaptic drive from On and Off bipolar cells, respectively. Taken together, our results suggest that the regulation of patterned spontaneous activity by neurotransmitters undergoes systematic change as new cellular elements are added to developing circuits and also that these new elements can help specify distinct activity patterns appropriate for shaping connectivity patterns at later ages.

2-Amino-5-phosphonovalerate↗

Influence of synaptic identity on single-Ia-afferent connectivity and EPSP amplitude in the adult cat: homonymous versus heteronymous connections.

1. This study makes use of the pattern of synaptic connections between motoneurons and Ia afferents of triceps surae muscles in the cat to test the relative importance of synaptic identity, neuronal size, and neuronal topography as determinants of Ia-afferent connectivity and excitatory postsynaptic potential (EPSP) amplitude. 2. The synaptic actions of single-Ia medial gastrocnemius (MG) afferents were measured by intracellular recording in MG and lateral gastrocnemius (LG) motoneurons. The spike-triggered averaging technique was used to measure EPSPs generated by homonymous or heteronymous Ia afferents and motoneurons, i.e., neurons supplying the same or different muscles, respectively. In agreement with earlier studies, the pooled sample showed that the number of functional connections and the size of EPSPs were both significantly greater for homonymous than for heteronymous neurons. 3. Afferent conduction velocity, motoneuron conduction velocity, rheobase current, and position of the motoneuron relative to the spinal cord afferent entry were all correlated with EPSP amplitude, but the amplitude difference between homonymous and heteronymous connections remained significant after the statistical removal analysis of covariance (ANCOVA) of the contribution of these variables. Stepwise multiple-regression analysis showed that synaptic identity explained the greatest fraction of the variance in EPSP amplitude (9%), with significant but smaller fractions accounted for by rheobase current or motoneuron conduction velocity. 4. In a separate experiment, the monosynaptic affects from both homonymous and heteronymous single-Ia afferents were examined in each of 88 MG or LG motoneurons. The single-Ia afferents used in this portion of the study were sampled from both MG and LG muscles and selected for similar conduction velocities and spinal cord entry points.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

[Investigation of the cerebral projection of the vestibular system using positron emission tomography].

The authors investigated the cerebral projection of the vestibular system, using positron emission tomography, in right-handed subjects. Both sided cold caloric stimulation was used in every volunteer (n = 6). A detailed map of activated and deactivated brain regions is included. This portrays changes caused by vestibular stimulation. The contralaterally activated regions according to the stimulation side were: postcentral gyrus, transvers temporal gyrus, superior temporal gyrus, posterior part of the insula, claustrum, putamen, inferior parietal lobule, precentral gyrus, premotor cortex, cingulate gyrus. The ipsilaterally activated regions were: transvers temporal gyrus, superior temporal gyrus, inferior parietal lobule, posterior part of the insula. There was no hemispherial dominance. The activated regions partially correspond with previous results in the literature. It would like to be pointed out the Brodmann 6 region as the cortical manifestation of involuntary isometric tightening of muscles. The contralaterally deactivated regions were: inferior, superior and medius temporal gyrus, medial and medius frontal gyrus, inferior occipital gyrus, parahippocampal gyrus and hippocampus. Ipsilaterally deactivated regions were: superior and medial frontal gyrus, inferior temporal gyrus, angular gyrus, parahippocampal gyrus and hippocampus, fusiform and inferior occipital gyrus. There was prominent hemispherial dominance in the stimulated, ipsilateral side. The deactivation based functional connection between the hippocampus and the vestibular system was pointed out in such a relation for the first time in this report.

Adult↗

Cadherin expression in the retina and retinofugal pathways of the chicken embryo.

The expression of two calcium-dependent adhesion molecules of the cadherin superfamily (cadherin-6B and cadherin-7) was mapped in the embryonic neural retina and retinofugal pathways of the chicken embryo and compared with the expression of R-cadherin, N-cadherin, and B-cadherin, studied previously. Whereas B-cadherin is only found in Miller glia, the other four cadherins are each expressed by specific subpopulations of retinal neurons. For example, different (but partly overlapping) populations of bipolar cells express R-cadherin, cadherin-6B, and cadherin-7. Cadherin-6B and cadherin-7 are also expressed by subsets of amacrine cells. In the inner plexiform layer, cadherin-6B and cadherin-7 immunoreactivities are restricted to specific sublaminae associated with synapsin-I-positive nerve terminals. In addition, cadherin-6B and cadherin-7 are expressed by a subset of ganglion cells that project to several retinorecipient nuclei forming part of the accessory optic system (e.g., nucleus of the basal optic root and external pretectal nucleus). Together with their connecting fiber tracts, these nuclei also express cadherin-6B and cadherin-7 in their neurons and neuropile. The expression patterns of the two cadherins overlap but show distinct differences. Some other visual nuclei express cadherin-7 but not cadherin-6B. The expression patterns differ from those previously described for N- and R-cadherin. Together, these results demonstrate that cadherins could provide a system of adhesive cues that specify developing retinal circuits and other functional connections and subsystems in the embryonic chicken visual system.

Animals↗

Postnatal development of the monkey's visual system.

The sudden increase of nervous activity after birth may influence the development of many parts of the brain. The visual system provides a particularly striking example of the crucial significance of birth itself in the maturation of the nervous system, for visual experience is obviously unlikely in utero. The role of the activity of afferent neurons in maintaining, even guiding, the formation of functional connections in the visual pathways has been extensively studied in a variety of species: such work in primates might give insight into the same process in man and into the aetiology of certain developmental disorders of vision. We have performed anatomical and physiological experiments on the monkey's lateral geniculate nucleus (LGN), which receives input from the optic nerves, and the primary visual cortex, to which the LGN sends its axons. In both structures there are enormous functional changes after birth, but those in the LGN seem not to depend on normal visual stimulation while those in the cortex seem crucially dependent on visual input.

Animals↗