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Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates, and in the lateral line organ of fishes. Through mechanotransduction, hair cells detect movement in their environment. In mammals, the auditory hair cells are located within the spiral organ of Corti on the thin basilar membrane in the cochlea of the inner ear. They derive their name from the tufts of stereocilia called hair bundles that protrude from the apical surface of the cell into the fluid-filled cochlear duct. The stereocilia number from fifty to a hundred in each cell while being tightly packed together and decrease in size the further away they are located from the kinocilium. The hair bundles are arranged as stiff columns that move at their base in response to stimuli applied to the tips. Mammalian cochlear hair cells are of two anatomically and functionally distinct types, known as outer, and inner hair cells. Damage to these hair cells results in

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Cochlea

The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the co

Auditory system

The auditory system is the sensory system for the sense of hearing. It includes both the sensory organs (the ears) and the auditory parts of the sensory system. Syst

Sensory neuron

Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded receptor potential

PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation

Sylvain Frédéric Bessonnard, Daniel Constam

The first cell differentiation in mammalian embryos segregates polarized trophectoderm cells from an apolar inner cell mass (ICM). This lineage decision is specified in compacted morulae by cell polarization and adhesion acting on the Yes-associated protein in the Hippo signaling pathway, but the regulatory mechanisms are unclear. We show that morula compaction and ICM formation depend on PC7 and the related proprotein convertases (PCs) Furin and Pace4 and that these proteases jointly regulate cell-cell adhesion mediated by E-cadherin processing. We also mapped the spatiotemporal activity profiles of these proteases by live imaging of a transgenic reporter substrate in wild-type and PC mutant embryos. Differential inhibition by a common inhibitor revealed that all three PCs are active in inner and outer cells, but in partially nonoverlapping compartments. E-cadherin processing by multiple PCs emerges as a novel mechanism to modulate cell-cell adhesion and fate allocation.

Rockefeller Univ Press2015

Control of Exocytosis by Synaptotagmins and Otoferlin in Auditory Hair Cells

Ralf Schneggenburger

In pre-hearing mice, vesicle exocytosis at cochlear inner hair cell (IHC) ribbon synapses is triggered by spontaneous Ca2+ spikes. At the onset of hearing, IHC exocytosis is then exclusively driven by graded potentials, and is characterized by higher Ca2+ efficiency and improved synchronization of vesicular release. The molecular players involved in this transition are still unknown. Here we addressed the involvement of synaptotagmins and otoferlin as putative Ca2+ sensors in IHC exocytosis during postnatal maturation of the cochlea. Using cell capacitance measurements, we showed that Ca2+-evoked exocytosis in mouse IHCs switches from an otoferlin-independent to an otoferlin-dependent mechanism at postnatal day 4. During this early exocytotic period, several synaptotagmins (Syts), including Syt1, Syt2 and Syt7, were detected in IHCs. The exocytotic response as well as the release of the readily releasable vesicle pool (RRP) was, however, unchanged in newborn mutant mice lacking Syt1, Syt2 or Syt7 (Syt1(-/-), Syt2(-/-) and Syt7(-/-) mice). We only found a defect in RRP recovery in Syt1(-/-) mice which was apparent as a strongly reduced response to repetitive stimulations. In post-hearing Syt2(-/-) and Syt7(-/-) mutant mice, IHC synaptic exocytosis was unaffected. The transient expression of Syt1 and Syt2, which were no longer detected in IHCs after the onset of hearing, indicates that these two most common Ca2+-sensors in CNS synapses are not involved in mature IHCs. We suggest that otoferlin underlies highly efficient Ca2+-dependent membrane-membrane fusion, a process likely essential to increase the probability and synchrony of vesicle fusion events at the mature IHC ribbon synapse.

Society for Neuroscience2010

Stiffness tomography exploration of living and fixed macrophages

Giovanni Dietler, Sandor Kasas, Giovanni Longo, Charles Roduit, Bhaskar Saha, Andrea Volterra

Stiffness tomography is a new atomic force microscopy imaging technique that allows highlighting structures located underneath the surface of the sample. In this imaging mode, such structures are identified by investigating their mechanical properties. We present here, for the first time, a description of the use of this technique to acquire detailed stiffness maps of fixed and living macrophages. Indeed, the mechanical properties of several macrophages were studied through stiffness tomography imaging, allowing some insight of the structures lying below the cell's surface. Through these investigations, we were able to evidence the presence and properties of stiff column-like features located underneath the cell membrane. To our knowledge, this is the first evidence of the presence, underneath the cell membrane, of such stiff features, which are in dimension and form compatible with phagosomes. Moreover, by exposing the cells to cytochalasin, we were able to study the induced modifications, obtaining an indication of the location and mechanical properties of the actin cytoskeleton. Copyright (C) 2012 John Wiley & Sons, Ltd.

Wiley-Blackwell2012

BIO-311: Neuroscience

The course starts with fundamentals of electrical - and chemical signaling in neurons. Students then learn how neurons in the brain receive and process sensory information, and how other neurons control the behavior of an animal. Furthermore, memory, learning, and brain disorders will be introduced.

BIOENG-448: Fundamentals of neuroengineering

Neuroengineering is at the frontier between neuroscience and engineering: understanding how the brain works allows developing engineering applications and therapies of high impact, while the design of new measurement and data analysis techniques contributes to advance our knowledge about the brain.

EE-348: Electroacoustics

Ce cours a pour objectif de former les étudiants de section Génie Electrique et Electronique à la conception de systèmes acoustiques, à l'aide d'un formalisme basé sur l'électrotechnique. A la fin du semestre, les étudiants seront capables de dimensionner, entre autres, des filtres acoustiques.