Vagal nerve stimulation therapy: what is being stimulated?

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity

Connections of the corpus cerebelli in the green sunfish and the common goldfish

Examination of the connections of the corpus cerebelli in one perciform (Lepomis cyanellus) and one cypriniform teleost (Carassius auratus) reveal that ipsilateral afferent connections in both species arise from an anterior group of nuclei in the diencephalon and mesencephalon, and a posterior group of nuclei in the rhombencephalon. Some nuclei of the anterior group and all those of the posterior group have in addition a weaker, and the medial octavolateralis nucleus a stronger, contralateral component. The inferior olivary nucleus in both species projects solely contralaterally. Nucleus paracommissuralis, the ventral accessory optic nucleus and nucleus isthmi are minute in Carassius compared to Lepomis. The latter species has in addition a bilateral corpopetal projection (ipsilaterally stronger) from the lateral cuneate nucleus. Efferent fibers in both species reach the contralateral nucleus ruber, oculomotor nucleus, nucleus of the medial longitudinal fasciculus, torus semicircularis, ventromedial and ventrolateral thalamic nuclei, optic tectum and superior and inferior reticular formation. An additional weaker ipsilateral terminal field could be observed in all nuclei except in the ventrolateral and ventromedial thalamic nuclei, the dorsal periventricular pretectal nucleus and the optic tectum. Lepomis in addition has a bilateral terminal field in the ventral accessory optic nucleus (contralaterally stronger). In both species, stronger ipsilateral and weaker contralateral terminal fields were present in the torus Iongitudinalis and the valvula cerebelli. The two patterns of corpopetal connections in Lepomis and Carassius were used as models for perciforms and cypriniforms in the analysis of the existing information in the literature on teleosts. While most discrepancies in the literature on percomorphs and ostariophysines could be interpreted consistently, the available information on mormyrids revealed a very different pattern of corpopetal organization: presence of additional connections (from a division of the nucleus preglomerulosus) and absence of otherwise well-established corpopetal connections in teleosts. In a second step, a phyletic analysis of teleostean corpopetal organization revealed that while teleosts share with all other vertebrates a group of corpopetal connections from the rhombencephalon, they evolved many new, more anteriorly located afferent inputs to the corpus cerebelli. Furthermore, electroreceptive mormyrids in addition evolved newly at least one corpopetal connection and lost many others

Increased bradykinesia in Parkinson’s disease with increased movement complexity: elbow flexion-extension movements

The present research investigates factors contributing to bradykinesia in the control of simple and complex voluntary limb movement in Parkinson’s disease (PD) patients. The functional scheme of the basal ganglia (BG)–thalamocortical circuit was described by a mathematical model based on the mean firing rates of BG nuclei. PD was simulated as a reduction in dopamine levels, and a loss of functional segregation between two competing motor modules. In order to compare model simulations with performed movements, flexion and extension at the elbow joint is taken as a test case. Results indicated that loss of segregation contributed to bradykinesia due to interference between competing modules and a reduced ability to suppress unwanted movements. Additionally, excessive neurotransmitter depletion is predicted as a possible mechanism for the increased difficulty in performing complex movements. The simulation results showed that the model is in qualitative agreement with the results from movement experiments on PD patients and healthy subjects. Furthermore, based on changes in the firing rate of BG nuclei, the model demonstrated that the effective mechanism of Deep Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of STN, partial synaptic failure of efferent projections, or excitation of inhibitory afferent axons even though the underlying methods of action may be quite different for the different mechanisms

A frequency-selective feedback model of auditory efferent suppression and its implications for the recognition of speech in noise

The potential contribution of the peripheral auditory efferent system to our understanding of speech in a background of competing noise was studied using a computer model of the auditory periphery and assessed using an automatic speech recognition system. A previous study had shown that a fixed efferent attenuation applied to all channels of a multi-channel model could improve the recognition of connected digit triplets in noise [G. J. Brown, R. T. Ferry, and R. Meddis, J. Acoust. Soc. Am. 127, 943?954 (2010)]. In the current study an anatomically justified feedback loop was used to automatically regulate separate attenuation values for each auditory channel. This arrangement resulted in a further enhancement of speech recognition over fixed-attenuation conditions. Comparisons between multi-talker babble and pink noise interference conditions suggest that the benefit originates from the model?s ability to modify the amount of suppression in each channel separately according to the spectral shape of the interfering sounds

Visual and Electrosensory Circuits of the Diencephalon in Mormyrids

Mormyrids are one of two groups of teleost fishes known to have evolved electroreception, and the concomitant neuroanatomical changes have confounded the interpretation of many of their brain areas in a comparative context, e.g., the diencephalon, where different sensory systems are processed and relayed. Recently, cerebellar and retinal connections of the diencephalon in mormyrids were reported. The present study reports on the telencephalic and tectal connections, specifically in Gnathonemus petersii, as these data are critical for an accurate interpretation of diencephalic nuclei in teleosts. Injections of horseradish peroxidase into the telencephalon retrogradely labeled neurons ipsilaterally in various thalamic, preglomerular, and tuberal nuclei, the nucleus of the locus coeruleus (also contralaterally), the superior raphe, and portions of the nucleus lateralis valvulae. Telencephalic injections anterogradely labeled the dorsal preglomerular and the dorsal tegmental nuclei bilaterally. Injections into the optic tectum retrogradely labeled neurons bilaterally in the central zone of area dorsalis telencephali and ipsilaterally in the torus longitudinalis, various thalamic, pretectal, and tegmental nuclei, some nuclei in the torus semicircularis, the nucleus of the locus coeruleus, the nucleus isthmi and the superior reticular formation, basal cells in the ipsilateral valvula cerebelli, and eurydendroid cells in the contralateral lobe C4 of the corpus cerebelli. Weaker contralateral projections were also observed to arise from the ventromedial thalamus and various pretectal and tegmental nuclei, and from the locus coeruleus and superior reticular formation. Tectal injections anterogradely labeled various pretectal nuclei bilaterally, as well as ipsilaterally the dorsal preglomerular and dorsal posterior thalamic nuclei, some nuclei in the torus semicircularis, the dorsal tegmental nucleus, nucleus isthmi, and, again bilaterally, the superior reticular formation. A comparison of retinal, cerebellar, tectal, and telencephalic connections in Gnathonemus with those in nonelectrosensory teleosts reveals several points: (1 the visual area of the diencephalon is highly reduced in Gnathonemus, (2) the interconnections between the preglomerular area and telencephalon in Gnathonemus are unusually well developed compared to those in other teleosts, and (3) two of the three corpopetal diencephalic nuclei are homologues of the central and dorsal periventricular pretectum in other teleosts. The third is a subdivision of the preglomerular area, rather than an accessory optic or pretectal nucleus, and is related to electroreception. The preglomerulo-cerebellar connections in Gnathonemus are therefore interpreted as uniquely derived characters for mormyrids

Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier.

The dynamic adjustment of hearing sensitivity and frequency selectivity is mediated by the medial olivocochlear efferent reflex, which suppresses the gain of the 'cochlear amplifier' in each ear. Such efferent feedback is important for promoting discrimination of sounds in background noise, sound localization and protecting the cochleae from acoustic overstimulation. However, the sensory driver for the olivocochlear reflex is unknown. Here, we resolve this longstanding question using a mouse model null for the gene encoding the type III intermediate filament peripherin (Prph). Prph((-/-)) mice lacked type II spiral ganglion neuron innervation of the outer hair cells, whereas innervation of the inner hair cells by type I spiral ganglion neurons was normal. Compared with Prph((+/+)) controls, both contralateral and ipsilateral olivocochlear efferent-mediated suppression of the cochlear amplifier were absent in Prph((-/-)) mice, demonstrating that outer hair cells and their type II afferents constitute the sensory drive for the olivocochlear efferent reflex

Activity of nAChRs containing α9 subunits modulates synapse stabilization via bidirectional signaling programs

Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) α9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR α9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in α9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the α9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult α9 null mice. Finally, by using mice expressing the nondesensitizing α9 L90T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation. © 2009 Wiley Periodicals, Inc.Fil: Murthy, Vidya. Tufts University School of Medicine; EslovaquiaFil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University School of Medicine; EslovaquiaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: Vetter, Douglas E.. Tufts University School of Medicine; Eslovaqui

Phaseolus vulgaris leuco-agglutinin immunohistochemistry. A comparison between autoradiographic and lectin tracing of neuronal efferents

The autoradiographic pattern of anterograde labeling as a result from injections with tritiated amino acids is compared to the labeling of efferents with Phaseolus vulgaris leuco-agglutinin after lectin injections in the same nucleus visualized by immunohistochemical methods. This comparison is made for efferents from the ventromedial hypothalamic nucleus to the amygdaloid body.