scholarly journals Intrinsic mechanical sensitivity of auditory neurons as a contributor to sound-driven neural activity

2021 ◽  
Author(s):  
Ebenezer N Yamoah ◽  
Maria C Perez Flores ◽  
Eric Verschooten ◽  
Jeong Han Lee ◽  
Hyo Jeong Kim ◽  
...  

Mechanosensation – by which mechanical stimuli are converted into a neuronal signal – is the basis for the sensory systems of hearing, balance, and touch. Mechanosensation is unmatched in speed and its diverse range of sensitivities, reaching its highest temporal limits with the sense of hearing; however, hair cells (HCs) and the auditory nerve (AN) serve as obligatory bottlenecks for sounds to engage the brain. Like other sensory neurons, auditory neurons use the canonical pathway for neurotransmission and millisecond-duration action potentials (APs). How the auditory system utilizes the relatively slow transmission mechanisms to achieve ultrafast speed and high audio-frequency hearing remains an enigma. Here, we address this paradox and report that the AN is mechanically sensitive, and minute mechanical displacement profoundly affects its response properties. Sound-mimicking sinusoidal mechanical and electrical current stimuli affect phase-locked responses. In a phase-dependent manner, the two stimuli can also evoke suppressive responses. We propose that mechanical sensitivity interacts with synaptic responses to shape responses in the AN, including frequency tuning and temporal phase-locking. The combination of neurotransmission and mechanical sensation to control spike patterns gives the AN a secondary receptor role, an emerging theme in primary neuronal functions.

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 384 ◽  
Author(s):  
Utku M. Sonmez ◽  
Adam Wood ◽  
Kyle Justus ◽  
Weijian Jiang ◽  
Fatima Syed-Picard ◽  
...  

Gradients of soluble molecules coordinate cellular communication in a diverse range of multicellular systems. Chemokine-driven chemotaxis is a key orchestrator of cell movement during organ development, immune response and cancer progression. Chemotaxis assays capable of examining cell responses to different chemokines in the context of various extracellular matrices will be crucial to characterize directed cell motion in conditions which mimic whole tissue conditions. Here, a microfluidic device which can generate different chemokine patterns in flow-free gradient chambers while controlling surface extracellular matrix (ECM) to study chemotaxis either at the population level or at the single cell level with high resolution imaging is presented. The device is produced by combining additive manufacturing (AM) and soft lithography. Generation of concentration gradients in the device were simulated and experimentally validated. Then, stable gradients were applied to modulate chemotaxis and chemokinetic response of Jurkat cells as a model for T lymphocyte motility. Live imaging of the gradient chambers allowed to track and quantify Jurkat cell migration patterns. Using this system, it has been found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. The chemotaxis of the Jurkat cells was also found to be governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Distinct migratory behaviors in response to chemokine gradients in different contexts may be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Our approach demonstrates the feasibility of using a flow-free gradient chamber for evaluating cross-regulation of cell motility by multiple factors in different biologic processes.


2021 ◽  
pp. 2000417
Author(s):  
Luigi Consolino ◽  
Annamaria Campa ◽  
Michele De Regis ◽  
Francesco Cappelli ◽  
Giacomo Scalari ◽  
...  

1992 ◽  
Vol 67 (2) ◽  
pp. 411-429 ◽  
Author(s):  
A. B. Turman ◽  
D. G. Ferrington ◽  
S. Ghosh ◽  
J. W. Morley ◽  
M. J. Rowe

1. Localized cortical cooling was employed in anesthetized cats for the rapid reversible inactivation of the distal forelimb region within the primary somatosensory cortex (SI). The aim was to examine the responsiveness of individual neurons in the second somatosensory area (SII) in association with SI inactivation to evaluate the relative importance for tactile processing of the direct thalamocortical projection to SII and the indirect projection from the thalamus to SII via an intracortical path through SI. 2. Response features were examined quantitatively before, during, and after SI inactivation for 29 SII neurons, the tactile receptive fields of which were on the glabrous or hairy skin of the distal forelimb. Controlled mechanical stimuli that consisted of l-s trains of either sinusoidal vibration or rectangular pulses were delivered to the skin by means of small circular probes (4- to 8-mm diam). 3. Twenty-three of the 29 SII neurons (80%) showed no change in response level (in impulses per second) as a result of SI inactivation. These included seven neurons activated exclusively or predominantly by Pacinian corpuscle (PC) receptors, six that received hair follicle input, four activated by convergent input from hairy and glabrous skin, and six driven by dynamically sensitive but non-PC inputs from the glabrous skin. 4. Six SII neurons (20%), also made up of different functional classes, displayed a reduction in response to cutaneous stimuli when SI was inactivated. 5. Stimulus-response relations, constructed by plotting response level in impulses per second against the amplitude of the mechanical stimulus, showed that the effect of SI inactivation on individual neurons was consistent over the whole response range. 6. The reduced response level seen in 20% of SII neurons in association with SI inactivation cannot be attributed to direct spread of cooling from SI to the forelimb area of SII, as there was no evidence for a cooling-induced prolongation in SII spike waveforms, an effect that is known to precede any cooling-induced reduction in responsiveness. 7. As SI inactivation produced a fall in spontaneous activity in the affected SII neurons, we suggest that the inactivation removes a source of background facilitatory influence that arises in SI and affects a small proportion of SII neurons. 8. Phase-locking and therefore the precision of impulse patterning were unchanged in the responses of SII neurons to vibration during SI inactivation. This was the case whether response levels of neurons were reduced or unchanged by SI inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mathiang G. Chot ◽  
Sarah Tran ◽  
Huiming Zhang

Abstract The perception of a sound can be influenced by another sound in a space-dependent manner. An understanding of this perceptual phenomenon depends on knowledge about how the spatial relationship between two sounds affects neural responses to the sounds. We used the rat as a model system and equal-probability two-tone sequences as stimuli to evaluate how spatial separation between two asynchronously recurring sounds affected responses to the sounds in midbrain auditory neurons. We found that responses elicited by two tone bursts when they were colocalized at the ear contralateral to the neuron were different from the responses elicited by the same sounds when they were separated with one at the contralateral ear while the other at another location. For neurons with transient sound-driven firing and not responsive to stimulation presented at the ipsilateral ear, the response to a sound with a fixed location at the contralateral ear was enhanced when the second sound was separated. These neurons were likely important for detecting a sound in the presence of a spatially separated competing sound. Our results suggest that mechanisms underlying effects of spatial separation on neural responses to sounds may include adaptation and long-lasting binaural excitatory/inhibitory interaction.


2008 ◽  
Vol 100 (3) ◽  
pp. 1384-1396 ◽  
Author(s):  
Weiqing Ji ◽  
Nobuo Suga

Experience-dependent plastic changes in the central sensory systems are due to activation of both the sensory and neuromodulatory systems. Nonspecific changes of cortical auditory neurons elicited by pseudoconditioning are quite different from tone-specific changes of the neurons elicited by auditory fear conditioning. Therefore the neural circuit evoking the nonspecific changes must also be different from that evoking the tone-specific changes. We first examined changes in the response properties of cortical auditory neurons of the big brown bat elicited by pseudoconditioning with unpaired tonal (CSu) and electric leg (USu) stimuli and found that it elicited nonspecific changes to CSu (a heart-rate decrease, an auditory response increase, a broadening of frequency tuning, and a decrease in threshold) and, in addition, a small tone-specific change to CSu (a small short-lasting best-frequency shift) only when CSu frequency was 5 kHz lower than the best frequency of a recorded neuron. We then examined the effects of drugs on the cortical changes elicited by the pseudoconditioning. The development of the nonspecific changes was scarcely affected by atropine (a muscarinic cholinergic receptor antagonist) and mecamylamine (a nicotinic cholinergic receptor antagonist) applied to the auditory cortex and by muscimol (a GABAA-receptor agonist) applied to the somatosensory cortex. However, these drugs abolished the small short-lasting tone-specific change as they abolished the large long-lasting tone-specific change elicited by auditory fear conditioning. Our current results indicate that, different from the tone-specific change, the nonspecific changes depend on neither the cholinergic neuromodulator nor the somatosensory cortex.


2011 ◽  
Vol 5 ◽  
pp. JEN.S6833
Author(s):  
Kenjiro Seki ◽  
Troy Templeton ◽  
Liisa A. Tremere ◽  
Raphael Pinaud

The balance between excitation and inhibition is critical in shaping receptive field tuning properties in sensory neurons and, ultimately, in determining how sensory cues are extracted, transformed and interpreted by brain circuits. New findings suggest that developmentally-regulated, experience-dependent changes in intracortical inhibitory networks are key to defning receptive field tuning properties of auditory cortical neurons.


2008 ◽  
Vol 295 (6) ◽  
pp. C1579-C1589 ◽  
Author(s):  
Wei-Chun Wei ◽  
Hsi-Hui Lin ◽  
Meng-Ru Shen ◽  
Ming-Jer Tang

Mechanical stimuli are essential during development and tumorigenesis. However, how cells sense their physical environment under low rigidity is still unknown. Here we show that low rigidity of collagen gel downregulates β1-integrin activation, clustering, and focal adhesion kinase (FAK) Y397 phosphorylation, which is mediated by delayed raft formation. Moreover, overexpression of autoclustered β1-integrin (V737N), but not constitutively active β1-integrin (G429N), rescues FAKY397 phosphorylation level suppressed by low substratum rigidity. Using fluorescence resonance energy transfer to assess β1-integrin clustering, we have found that substratum rigidity between 58 and 386 Pa triggers β1-integrin clustering in a dose-dependent manner, which is highly dependent on actin filaments but not microtubules. Furthermore, augmentation of β1-integrin clustering enhances the interaction between β1-integrin, FAK, and talin. Our results indicate that contact with collagen fibrils is not sufficient for integrin activation. However, substratum rigidity is required for integrin clustering and activation. Together, our findings provide new insight into the mechanosensing machinery and the mode of action for epithelial cells in response to their physical environment under low rigidity.


2001 ◽  
Vol 86 (2) ◽  
pp. 1062-1066 ◽  
Author(s):  
Bernhard H. Gaese ◽  
Joachim Ostwald

The vast majority of investigations on central auditory processing so far were conducted under the influence of an anesthetic agent. It remains unclear, however, to what extend even basic response properties of central auditory neurons are influenced by this experimental manipulation. We used a combination of chronic recording in unrestrained animals, computer-controlled randomized acoustic stimulation, and statistical evaluation of responses to directly compare the response characteristics of single neurons in the awake and anesthetized state. Thereby we were able to quantify the effects of pentobarbital/chloral hydrate anesthesia (Equithesin) on rat auditory cortical neurons. During Equithesin anesthesia, only a portion of central neurons were active and some of their basic response properties were changed. Only 29% of the neurons still had a frequency response area. Their tuning sharpness was increased under anesthesia. Most changes are consistent with an enhancement of inhibitory influences during Equithesin anesthesia. Thus when describing response properties of central auditory neurons, the animal's anesthetic state has to be taken into account.


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