Jérémie
      Barral
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The sensory world is a fascinating system. Far from being immobile, we constantly actuate our perception of the external world. Detection, perception, transformation or treatment of sensory or cognitive information involve the activity of complex dynamical systems.

Neuronal networks

Over the past decade, there have been a number of seminal theories on the conditions for propagating information faithfully while maintaining stability in neuronal networks. However, to maintain mathematical tractability, these studies relied heavily on principles borrowed from physics. While the concepts are universally applicable to all neural networks (sensory, motor, higher cognitive areas), they are necessarily abstract and make simplifying assumptions that appear far from biological parameters. Testing these theories is very difficult as it requires accurate information about the network architecture and the precise control of the input to the network. For example, assessing function in the intact, in vivo preparation is challenging as it has too many variables that need to be controlled (e.g. whether the animal is anesthetized, alert, moving, head-fixed, etc.).

To overcome these limitations, we use the culture preparation in combination with microfabrication and stimulated our network using a novel optogenetic stimulation technique. This allowed us to vary systematically network density and architecture, measure synaptic connections, and drive the network with any specified input (see movie). We showed that in neuronal cultures, synaptic strengths scale with the network size to preserve balance between excitation and inhibition, maintain variable spiking statistics and reduce correlations in spiking as predicted by theory and observed in the intact brain (see Barral et al (2016)).




Schematic of the optogenetic setup (top) used to stimulate with high spatial and temporal resolution a predefined number of neurons with any specified input (bottom).
Hearing


View of a single hair cell extracted from the saccule of the bullfrog (Rana catesbeiana). The mechanical antenna (hair bundle) protrudes at the apical surface and is composed of about 50 stereocilia that are arranged in rows of increasing height.



Hearing relies on the ear’s ability to detect sound-evoked vibrations. My PhD focused on understanding how sensory hair cells act simultaneously as cellular microphones and as mechanical amplifiers. At the interface between physics and biology, my research project aimed at shedding light on the amplificatory process that shapes the sensation of sounds at the periphery of the auditory system.

The vertebrate ear benefits from nonlinear mechanical amplification to operate over a vast range of sound intensities. The amplificatory process is thought to emerge from active force production by sensory hair cells. The mechano-sensory hair bundle that protrudes from the apical surface of each hair cell can oscillate spontaneously (see movie) and function as a frequency-selective, nonlinear amplifier.


Most hair bundles are mechanically coupled by overlying gelatinous structures. By combining dynamic force clamp of a hair bundle with stochastic simulations of hair-bundle mechanics, we could mimic a virtual environment in which a real hair-bundle is elastically coupled to two neighbors that are simulated in real time by a computer. We found that coupling increased the coherence of spontaneous hair-bundle oscillations by effectively reducing noise. We argue that the auditory amplifier relies on hair-bundle cooperation to overcome intrinsic noise limitations and achieve high sensitivity and sharp frequency selectivity (see Barral et al (2010), comments in Physics Today and Journal of Experimental Biology).

Nonlinear amplification is the price to pay for high sensitivity. Two-tone stimulation of a single hair bundle generates distortion products and manifests masking phenomena. We showed that the effects of nonlinear mechano-transduction are amplified near the characteristic frequency of spontaneous hair-bundle oscillations. We thus argue that human psychophysical observations, cochlear mechanics and active hair-bundle oscillations rely on the generic behaviour of active nonlinear oscillators that shapes the sensation of sounds at the periphery of the auditory system
(see Barral et al (2012), comments in Nature Physics).