Powerful, Onset Inhibition in the Ventral Nucleus of the Lateral Lemniscus

2005 ◽  
Vol 94 (2) ◽  
pp. 1651-1654 ◽  
Author(s):  
David A. X. Nayagam ◽  
Janine C. Clarey ◽  
Antonio G. Paolini

The function of the ventral nucleus of the lateral lemniscus (VNLL), a secondary processing site within the auditory brain stem, is unclear. It is known to be a major source of inhibition to the inferior colliculus (IC). It is also thought to play a role in coding the temporal aspects of sound, such as onsets and the periodic components of complex stimuli. In vivo intracellular recordings from VNLL neurons ( n = 56) in urethane anesthetized rats revealed the presence of large-amplitude, short-duration, onset inhibition in a subset of neurons (14.3%). This inhibition occurred before the first action potential (AP) elicited by noise or tone bursts, was broadly tuned to tonal frequency and was shown to delay the first AP. Our data suggest it is a result of an intrinsic circuit activated by the octopus cell pathway originating in the contralateral cochlear nucleus; this pathway is known to convey exquisitely timed and broadly tuned onset information. This powerful inhibition within the VNLL appears to control the timing of this structure's inhibitory output to higher centers, which has important auditory processing outcomes. The circuit also provides a pathway for fast, broadly tuned, onset inhibition to the IC.

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Daniel P Stewart ◽  
Suresh Marada ◽  
William J Bodeen ◽  
Ashley Truong ◽  
Sadie Miki Sakurada ◽  
...  

Hedgehog ligands activate an evolutionarily conserved signaling pathway that provides instructional cues during tissue morphogenesis, and when corrupted, contributes to developmental disorders and cancer. The transmembrane protein Dispatched is an essential component of the machinery that deploys Hedgehog family ligands from producing cells, and is absolutely required for signaling to long-range targets. Despite this crucial role, regulatory mechanisms controlling Dispatched activity remain largely undefined. Herein, we reveal vertebrate Dispatched is activated by proprotein convertase-mediated cleavage at a conserved processing site in its first extracellular loop. Dispatched processing occurs at the cell surface to instruct its membrane re-localization in polarized epithelial cells. Cleavage site mutation alters Dispatched membrane trafficking and reduces ligand release, leading to compromised pathway activity in vivo. As such, convertase-mediated cleavage is required for Dispatched maturation and functional competency in Hedgehog ligand-producing cells.


2006 ◽  
Vol 498 (2) ◽  
pp. 295-315 ◽  
Author(s):  
David A.X. Nayagam ◽  
Janine C. Clarey ◽  
Antonio G. Paolini
Keyword(s):  

Author(s):  
Ana Cláudia Mondini Ribeiro Bez ◽  
Cyntia Barbosa Laureano Luiz ◽  
Sabrina Mazzer Paes ◽  
Renata Rangel Azevedo ◽  
Daniela Gil

Abstract Introduction Dysphonia is an oral communication disorder. The voice and hearing are interrelated aspects. Hearing is an important sensory input for monitoring the vocal pattern. The relation between hearing abilities and dysphonia represents a contribution both in scientific and in clinical terms, especially in cases in which satisfactory results are not achieved in the therapeutic process. Objective To characterize long-latency auditory evoked potential (P300) with tonal and complex stimuli, and to make a behavioral evaluation of auditory processing in adults with behavioral dysphonia. Method The sample used for the present study consisted of 20 subjects from both genders with ages ranging from 18 and 58, who were diagnosed with behavioral dysphonia. The evaluations occurred in a single 2-hour session, in which the procedures of clinical history, pure tone and speech audiometries, acoustic immittance measures, and behavioral and electrophysiological evaluations of auditory processing were performed. Results The descriptive measures of P3 latency elicited by tonal and complex stimuli showed similar results for the right and left ears, without statistically significant differences. In the qualitative analysis, the results observed were within the normality patterns for the P3 component for both tonal and complex stimuli. As for the behavioral evaluation of auditory processing, abnormal results were observed in 100% of the sample. Abnormalities were found in the auditory skills of ordering and temporal resolution and figure-background obtained from the duration pattern, random gap detection, and dichotic tests (syllables and words), respectively. Conclusion The evaluated patients presented central auditory processing disorder, evidenced by behavioral assessment.


1995 ◽  
Vol 104 (3) ◽  
pp. 231-236 ◽  
Author(s):  
Tetsuya Ganbo ◽  
Tsukasa Nakajima ◽  
Ken-Ichi Hisamaisu ◽  
Hajime Inoue ◽  
Shin-Ichi Shimomura ◽  
...  

The effect of leukotrienes C4 (LTC4) and D4 (LTD4) and prostaglandin E2 (PGE2) on mucociliary clearance of the eustachian tube was investigated in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated separately with LTC4, LTD4, and PGE2 at concentrations of 10−8 mol/L and 10−6 mol/L. Ciliary activity was measured photoelectrically. Leukotriene D4 progressively inhibited ciliary activity, while PGE2 promoted it. Leukotriene C4 also induced ciliary inhibition. One milliliter each of 10−5 mol/L LTC4, LTD4, and PGE2 was directly injected into the tympanic bullae of chinchillas under anesthesia. The middle ears were examined by otomicroscopy, tympanometry, and auditory brain stem response over time. Clearance of middle ear effusion was delayed by LTC4 and LTD4, as compared with PGE2 and the control. These findings indicate that LTC4 and LTD4 inhibit mucociliary clearance of the eusiachian tube.


2007 ◽  
Vol 97 (2) ◽  
pp. 1775-1785 ◽  
Author(s):  
Keith N. Darrow ◽  
Stéphane F. Maison ◽  
M. Charles Liberman

Cochlear sensory cells and neurons receive efferent feedback from the olivocochlear (OC) system. The myelinated medial component of the OC system and its effects on outer hair cells (OHCs) have been implicated in protection from acoustic injury. The unmyelinated lateral (L)OC fibers target ipsilateral cochlear nerve dendrites and pharmacological studies suggest the LOC's dopaminergic component may protect these dendrites from excitotoxic effects of acoustic overexposure. Here, we explore LOC function in vivo by selective stereotaxic destruction of LOC cell bodies in mouse. Lesion success in removing the LOC, and sparing the medial (M)OC, was assessed by histological analysis of brain stem sections and cochlear whole mounts. Auditory brain stem responses (ABRs), a neural-based metric, and distortion product otoacoustic emissions (DPOAEs), an OHC-based metric, were measured in control and surgical mice. In cases where the LOC was at least partially destroyed, there were increases in suprathreshold neural responses that were frequency- and level-independent and not attributable to OHC-based effects. These interaural response asymmetries were not found in controls or in cases where the lesion missed the LOC. In LOC-lesion cases, after exposure to a traumatic stimulus, temporary threshold shifts were greater in the ipsilateral ear, but only when measured in the neural response; OHC-based measurements were always bilaterally symmetric, suggesting OHC vulnerability was unaffected. Interaural asymmetries in threshold shift were not found in either unlesioned controls or in cases that missed the LOC. These findings suggest that the LOC modulates cochlear nerve excitability and protects the cochlea from neural damage in acute acoustic injury.


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