OPTO-LOCO

Unraveling the circuits of locomotion with opto-genetic manipulation of neuronal activity in awake behaving animals

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 Obiettivo del progetto (Objective)

'Locomotion relies on neural networks called central pattern generators (CPGs) that generate periodic motor commands for rhythmic movements. The manipulation of electrical activity and cell signaling in specific neuron type using light gated receptors enables us today to dissect the specific neuronal circuits forming the CPGs, and understand the dynamic role of sensory inputs in awake behaving animals. During my work in UC Berkeley, I developed the use of light gated receptors in vivo (Szobota 2007, Pautot 2008 and Wyart 2009). This novel approach enables us to test directly the role of specific pattern of activity in genetically identified neurons for shaping the complex locomotor behaviors. Using a combination of targeted gene expression and optical tools for monitoring and manipulating neuronal activity (“optogenetics”) in awake behaving animals, we have revealed the role of mysterious cells present at the interface between the spinal cord and the central canal: the cerebrospinal fluid (CSF) contacting neurons. I demonstrated that during early development in low vertebrates these cells provide the positive drive to the spinal central pattern generators for spontaneous locomotion (Wyart et al 2009). My future plan focuses on investigating further the circuits of locomotion in the healthy and severed spinal cord. My project consists in three distinct aims: Aim 1. To examine the chemo- and mechano-sensory functions of spinal CSF-contacting neurons Aim 2. To elucidate the role of dynamic sensory feedback for triggering transitions during locomotion Aim 3. To improve recovery of function after spinal cord injury using optogenetics'

Introduzione (Teaser)

Any movement, however simple, is due to a highly complex coordination of nerve cell firing. EU research is delving into the details that specify the role of genetically identified neurons in locomotion.

Descrizione progetto (Article)

Mobility relies on networks of nerve cells or neurons, central pattern generators. These generate periodic motor commands to induce muscle contraction for rhythmic movement. By intermittently alternating muscle excitation and inhibition, muscle oscillation gives rise to the slow forward swim in zebra fish larvae.

Based on their previous research, the OPTO-LOCO project is using light-gated receptors in real-time. This helped test the function of genetically identified nerve cells that contribute to a specific pattern of activity. The scientists looked at cells at the interface between the spinal cord and the central canal, so-called cerebrospinal fluid contacting neurons (CSFns).

Using optogenetics, the combination of targeted gene expression and optical tools, the scientists are constructing the picture of movement in awake behaving animals. Remote manipulation and recording of nerve cell activity enabled the turning on and off of selected subsets of neurons over time. Through this, the team could determine which neuron must be fired to generate a particular movement. The method uses specific wavelengths of light on engineered proteins; muscle response is monitored with fluorescent proteins.

Using these ingenious techniques, OPTO-LOCO investigated how influences from chemo-, mechano- and thermo-sensory sources can determine the type of movement.

The scientists discovered that CSFn activity could modulate movement and in particular, slow forward swim. Movement would not be coordinated without the presence of proprioceptors, sensors that give critical information on muscle length and tension. Proprioceptors react to the contraction and tension or the relaxation and stretching of muscle.

In the last two years, the team has developed a new method for automatically tracking and phenotyping zebrafish larvae behaviour. The work has been published in 'Frontiers in Neural Circuits'.

Extending the research into higher animals, the team have identified a receptor as a marker of CSFns in vertebrates. Exciting news as there is now evidence that these neurons are present in vertebrates right up to primates. The results of OPTO-LOCO may open up new territory into the study of proprioceptors and movement in humans.