Activation of the neuronal-glial network in the spinal cord dorsal horn (SCDH) mediates various chronic painful conditions. We studied spinal neuronal-astrocyte signaling interactions involved in the maintenance of painful diabetic neuropathy (PDN) in type 2 diabetes. We used the db/db mouse, an animal model for PDN of type 2 diabetes, ...

OBJECTIVES: To evaluate whether augmenting neuronal protective mechanisms might slow or arrest experimental diabetic peripheral neuropathy (DPN). DPN is one of the most common neurodegenerative disorders and is rising in prevalence. How it targets sensory neurons is uncertain; the disorder is irreversible and untreatable. We explored the intrinsic protective properties ...

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in which hyperglycemia-induced mitochondrial dysfunction and enhanced oxidative stress contribute to sensory neuron pathology. KU-32 is a novobiocin-based, C-terminal inhibitor of the molecular chaperone, heat shock protein 90 (Hsp90). KU-32 ameliorates multiple sensory deficits associated with the progression of DPN ...

Brief contact of the duodenal mucosa with luminal acid elicits a long-lasting bicarbonate (HCO(3)(-)) secretory response, which is believed to be the primary protective mechanism against mucosal damage. Here, we show that cGMP-dependent protein kinase type I-knockout (cGKI(-/-)) mice are unable to respond to a physiological H(+) stimulus with a ...

Glycinergic neurons are the major inhibitory neurons in the vertebrate central nervous system. In teleosts, they play an important role in the escape response by regulating the activity of the Mauthner (M-) cells. Here we studied the contact between glycinergic axons and M-cells in early zebrafish embryos by double immunostaining ...

Dendrites, axons, and synapses are dynamic during circuit development; however, changes in microcircuit connections as branches stabilize have not been directly demonstrated. By combining in vivo time-lapse imaging of Xenopus tectal neurons with electron microscope reconstructions of imaged neurons, we report the distribution and ultrastructure of synapses on individual vertebrate neurons ...

The pathways by which painful stimuli are signaled within the human medial temporal lobe are unknown. Rodent studies have shown that nociceptive inputs are transmitted from the brainstem or thalamus through one of two pathways to the central nucleus of the amygdala. The indirect pathway projects from the basal and ...

Crickets use their long antennae as tactile sensors. Confronted with obstacles, conspecifics or predators, antennal contacts trigger short-latency motor responses. To reveal the neuronal pathway underlying these antennal-guided locomotory reactions we identified descending interneurons that rapidly transmit antennal-tactile information from the head to the thorax in the cricket Gryllus bimaculatus. ...

Motor and emotion processing depend on different fronto-basal ganglia circuits. Distinct sub-regions of the subthalamic nucleus (STN) may modulate these circuits. We evaluated whether stimulation targeted at separate territories in the STN region would differentially affect motor and emotion function. In a double-blind design, we studied twenty Parkinson's disease patients ...

We reported pharmacological data suggesting that stimulation of a vago-vagal reflex activates GABAergic neurons in the hindbrain that inhibit dorsal motor nucleus of the vagus (DMV) neurons projecting to the antrum, but not to the fundus (Ferreira et al., 2002). The purpose of this study was to use an ultrastructural ...

Cochlea removal results in the death of approximately 20-30% of neurons in the chick nucleus magnocellularis (NM). One early event in NM neuronal degradation is the disruption of their ribosomes. This can be visualized in the first few hours following cochlea removal using Y10B, an antibody that recognizes ribosomal RNA. ...

Acoustic information is brought to the brain by auditory nerve fibers, all of which terminate in the cochlear nuclei, and is passed up the auditory pathway through the principal cells of the cochlear nuclei. A population of neurons variously known as T stellate, type I multipolar, planar multipolar, or chopper ...

A 3-D application-specific microelectrode array has been developed for physiological studies in guinea pig cochlear nucleus (CN). The batch-fabricated silicon probes contain integrated parylene cables and use a boron etch-stop to define 15μm-thick shanks and limit tissue displacement. Targeting the ventral (three probes) and dorsal (two probes) subnuclei, the custom ...

A major limitation of the present auditory brainstem implant (ABI) is its inability to access the tonotopic organization of the ventral cochlear nucleus (VCN). A previous study by our group indicated that stimulation of single sites within a given VCN frequency region did not always elicit frequency-specific responses within the ...

OBJECTIVES/HYPOTHESIS: One limitation with cochlear implants is the difficulty stimulating spatially discrete spiral ganglion cell groups because of electrode interactions. Multipolar electrodes have improved on this some, but also at the cost of much higher device power consumption. Recently, it has been shown that spatially selective stimulation of the auditory ...

Neurons of the cochlear nuclei are anatomically and physiologically specialized to optimally encode temporal and spectral information about sound stimuli, in part for binaural auditory processing. The avian cochlear nucleus magnocellularis (NM) integrates excitatory eighth nerve inputs and depolarizing GABAergic inhibition such that temporal fidelity is enhanced across the synapse. ...

Elimination of the Kv1.3 voltage-dependent potassium channel gene produces striking changes in the function of the olfactory bulb, raising the possibility that this channel also influences other sensory systems. We have examined the cellular and subcellular localization of Kv1.3 in the medial nucleus of the trapezoid body (MNTB) in the ...

Animal models have demonstrated that mild hearing loss caused by acoustic trauma results in spontaneous hyperactivity in the central auditory pathways. This hyperactivity has been hypothesized to be involved in the generation of tinnitus, a phantom auditory sensation. We have recently shown that such hyperactivity, recorded in the inferior colliculus, ...

The developing sensory neurons of the mammalian ear require two sequentially activated bHLH genes, Neurog1 and Neurod1, for their development. Neurons never develop in Neurog1 null mice, and most neurons die in Neurod1 null mutants, a gene upregulated by Neurog1. The surviving neurons of Neurod1 null mice are incompletely characterized ...

We examined the response characteristics of primary auditory cortex (A1) neurons in adult cats partially but extensively deafened by ototoxic drugs 2-8 days after birth. The damage evoked extensive A1 topographic map reorganization as also found by others, but a novel finding was that in the majority of cats with ...

We have investigated the generation of the compound action potential (CAP) from the auditory nerve of guinea pigs. Responses to acoustic tone-bursts were recorded from the round window (RW), throughout the cochlear fluids, from the surface of the cochlear nucleus, from the central end of the auditory nerve after removal ...

Kv7.5/KCNQ5, a voltage-dependent potassium channel that generates a subthreshold K+ current (also called M-current), is localized in excitatory endings of auditory brainstem nuclei in the adult rat. Here, we focus on how specific targeting develops from birth to adulthood in the rat. We first analyzed by immunocytochemistry the distribution of ...

The effects of deafness on brain structure and function have been studied using animal models of congenital deafness that include surgical ablation of the organ of Corti, acoustic trauma, ototoxic drugs, and hereditary deafness. This report describes the morphologic plasticity of auditory nerve synapses in response to ototoxic deafening and ...

Lesion-induced neuroplasticity, including fiber degeneration, axonal growth, and synaptogenesis, involves dynamical changes of the extracellular matrix. We discovered that the matrix metalloprotease-2 (MMP-2), a major actor in extracellular matrix recomposition, is changed in distribution and increased in amount in the ventral cochlear nucleus after unilateral cochlear ablation. There was a ...

After a cochlear lesion or auditory nerve damage, afferent connections from auditory ganglia can be highly altered. This results in a clear reduction of auditory input and an alteration of connectivity of terminals on cochlear nuclei neurons. Such a process could stimulate the reorganization of the neural circuits and neuroplasticity. ...

Deaf people who use cochlear implants show surprisingly poor sensitivity to the temporal fine structure of sounds. One possible reason is that conventional cochlear implants cannot activate selectively the auditory-nerve fibers having low characteristic frequencies (CFs), which, in normal hearing, phase lock to stimulus fine structure. Recently, we tested in ...

Vertebrate inner-ear hair cells use mechanical feedback to amplify sound-induced vibrations. The gain of this 'cochlear amplifier' is centrally controlled via efferent fibres that, making synaptic contacts with the hair cells, modulate the feedback gain. The sensory neurons of the Drosophila ear likewise employ mechanical feedback to assist sound-evoked vibrations, ...

In the developing nervous system, neurotrophin 3 (NT3) and brain-derived neurotrophic factor (BDNF) have been shown to interact with each other and with different parts of a neuron or glia and over considerable distances in time and space. The auditory system provides a useful model for analyzing these events, insofar ...

Auditory brainstem implants (ABIs) restore hearing by electrical stimulation of the cochlear nucleus (CN). Depending on the physiological condition, duration of the pre-existing deafness, extent of damage to the CN, and the number of channels accessible to the tonotopic frequency gradients of the CN, ABIs improve speech understanding to varying ...

The mammalian cochlea is innervated by two classes of sensory neurons. Type I neurons make up 90-95% of the cochlear nerve and contact single inner hair cells to provide acoustic analysis as we know it. In contrast, the far less numerous type II neurons arborize extensively among outer hair cells ...

Neural recognition molecule NB-2/contactin 5 is expressed transiently during the first postnatal week in glutamatergic neurons of the central auditory system. Here, we investigated the effect of NB-2 deficiency on the auditory brainstem in mouse. While almost all principal neurons are wrapped with the calyces of Held in the medial ...

Autosomal dominant optic atrophy (DOA) is a retinal neuronal degenerative disease characterized by a progressive bilateral visual loss. We report on two affected members of a family with dominantly inherited neuropathy of both optic and auditory nerves expressed by impaired visual acuity, moderate pure tone hearing loss, and marked loss ...

Plasticity in the adult mammalian brain can occur after damage to peripheral nerves and has also been described in the auditory system. Acoustic trauma, resulting in a loss of cochlear sensitivity, can lead to elevated levels of spontaneous activity, that is hyperactivity, in central nuclei such as the inferior colliculus. ...

The cochlear nucleus (CN) is the first sound processing center in the central auditory system that receives the almost unprocessed auditory information from the auditory periphery. The functional organization of the CN has been studied to a great extent in many mammals, including the cat, rat and bat. Yet, despite ...

Conclusion. Unilateral congenital deafness with a volume reduction in cochlear nucleus (CN) induced changes in the calcium-binding proteins (CaBPs) in the contralateral superior olivary complex (SOC) in the rat. With the loss of neurons and a volume reduction in the CN, a decrease in the input to the contralateral SOC ...

CONCLUSION: The gentamicin-induced pathological alteration in the cochlear nucleus is not exclusively a secondary consequence of the damage in the cochlea. Instead, the toxic effect of gentamicin on the cochlear nucleus may occur simultaneously or even earlier than that on the cochlea. OBJECTIVES: To investigate the pathological alteration of cochlear ...

Complexins (CPXs I-IV) presumably act as regulators of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, but their function in the intact mammalian nervous system is not well established. Here, we explored the role of CPXs in the mouse auditory system. Hearing was impaired in CPX I knock-out mice ...

Much of what is known about how the cochlear nuclei participate in mammalian hearing comes from studies of non-primate mammalian species. To determine to what extent the cochlear nuclei of primates resemble those of other mammalian orders, we have recorded responses to sound in three primate species: marmosets, cynomolgus macaques, ...

In the normal guinea pig, contralateral sound inhibits more than a third of ventral cochlear nucleus (VCN) neurons but excites <4% of these neurons. However, unilateral conductive hearing loss (CHL) and cochlear ablation (CA) result in a major enhancement of contralateral excitation. The response properties of the contralateral excitation produced ...

Auditory brainstem implants (ABI) have been used in neurofibromatosis type 2 (NF2) patients in an attempt to restore hearing sensation, with limited clinical success. Factors associated with poor clinical outcomes for NF2 ABI patients include larger tumour size, longer duration of hearing loss, and brainstem distortion and/or deformation caused by ...

Nucleotides and nucleosides are known to function as neurotransmitters and neuromodulators but have recently been shown to have a trophic effect on neurons. It has previously been shown, in an animal model for cochlear implants, that local infusion of neurotrophic factors intervenes with the degenerative processes occurring after deafening and ...

The cochlear nucleus (CN), which consists of dorsal and ventral cochlear nuclei (DCN and VCN), plays pivotal roles in processing and relaying auditory information to the brain. Although it contains various types of neurons, the origins of the distinct subtypes and their developmental molecular machinery are still elusive. Here we ...

It is well established that the cochlear nucleus (CN) of developing species is susceptible to loss of synaptic connections from the auditory periphery. Less information is known about how de-afferentation affects the adult auditory system. We investigated the effects of de-afferentation to the adult CN by mechanical compression. This experimental ...

The nuclei of the auditory brainstem harbor a diversity of neuronal cell types and are interconnected by excitatory as well as inhibitory ascending, descending, and commissural pathways. Classically, neurons have been characterized by size and shape of their cell body and by the geometry of their dendrites. Our study is ...

Integration of multimodal information is essential for understanding complex environments. In the auditory system, multisensory integration first occurs in the cochlear nucleus (CN), where auditory nerve and somatosensory pathways converge (Shore, 2005). A unique feature of multisensory neurons is their propensity to receive cross-modal compensation after deafening. Based on our ...

While many factors contribute to aging, changes in calcium homeostasis and calcium related neuronal processes are likely to be important. High intracellular calcium is toxic to cells and alterations in calcium homeostasis are associated with changes in calcium-binding proteins, which confine free Ca(2+). We therefore assayed the expression of the ...

NB-2 is a neuronal cell recognition molecule that is preferentially expressed in auditory pathways. Mice deficient in the NB-2 gene exhibit aberrant responses to acoustic stimuli. Here we examined the expression and localization of NB-2 in the auditory brainstem during development in the rat. NB-2 was strongly expressed in the ...

Of the three major subdivisions of the auditory thalamus, the medial subdivision is the only one that receives a direct projection from the dorsal cochlear nucleus. Those cells in the medial auditory thalamus that receive the projection from the dorsal cochlear nucleus continue to the auditory cortex. A combination of ...

Spontaneous neural hyperactivity in the central auditory pathway is often associated with deafness, the most common form of which is partial hearing loss. We quantified both peripheral hearing loss and spontaneous activity in single neurons of the contralateral inferior colliculus in a guinea-pig model 1 week after a unilateral partial ...

Commissural neurons connect the cochlear nucleus complexes of both ears. Previous studies have suggested that the neurons may be separated into two anatomical subtypes on the basis of percent apposition (PA); that is, the percentage of the soma apposed by synaptic terminals. The present study combined tract tracing with synaptic ...