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Guillaume Dugué

I am a newly recruited CNRS Research Scientist (Chargé de Recherches) in Biology at IBENS, specialized in Neurosciences

I studied as an undergraduate at the ENS and University Pierre et Marie Curie between 2000 and 2002. At the time, the big questions that aroused my curiosity were how do neural circuits assemble themselves, and how do they work to make an animal move, feel and think ? Neurophysiology was just beginning to make a strong comeback after the revolution of molecular neurobiology, but I felt that starting my research work at the cellular level sounded like a reasonable choice before moving toward more integrated questions (the so-called “bottom-up” approach).

Between 2003 and 2007, I did my PhD with Stéphane Dieudonné, studying the properties of Golgi cells, a special type of inhibitory interneuron in the cerebellar cortex. I was working on acute brain slices using the patch clamp technique, and being able to tickle neurons electrically while directly looking at them was almost like a game. We found that Golgi cells load up and release two inhibitory neurotransmitters, GABA and glycine, but that these transmitters are used differentially at Golgi cells’ synapses with its two types of target neurons [1]. This was among the first examples of a target-specific communication between one presynaptic and two postsynaptic neurons using coreleased transmitters. We then found that Golgi cell firing can be shaped by mutual electrical interactions through gap junctions ; but unlike what had been shown and argued previously in other systems, Golgi cells tend to inhibit each other through the electrical transmission of their large after-hyperpolarization. With collaborators at the LPS (laboratoire de physique statistique), we showed that this “inhibitory” electrical effect could contribute to the emergence of synchronized rhythmic firing in the Golgi cell population [2] ; this property could allow Golgi cells to operate in phase with episodes of oscillating activity that are observed throughout the motor system.

For my first postdoc (between 2008 and 2011), I joined the lab of Zachary Mainen in Lisbon at the newly created Champalimaud Foundation. This was both a totally rejuvenating experience, with lots of new things to learn, and a tough confrontation with the unfairness of some types of experiments. Like many others at the time, I had embraced optogenetics and I was exploring how this just-emerging field could help us understand high-level functions using highly-specific manipulations. My work was to leverage the power of optogenetic photostimulation to find new evidence of the influence of serotonin-releasing (serotonergic) neurons on various aspects of behavior. Working with tools that were still unknown 3 years earlier was absolutely thrilling ; we were opening new trails in a virgin land. After several unsuccessful attempts, I finally established paradigms that allowed me to produce transient increases of serotonergic activity or to remotely monitor the activity of serotonergic neurons in awake mice. I showed in particular that during enhanced serotonergic activity, mice exhibit a decreased sensitivity to unpleasant tactile stimulations [3], an observation that might be linked to the existence of behavioral situations that can induce analgesia (for example frightening situations).

For my second postdoc, I decided to work on more tractable neuronal systems, whose influence on behavior can be more easily read out. This brought me back to the cerebellum, but this time at the systems level. I did my second postdoc in the team of Clément Léna and Daniela Popa at the IBENS, between 2012 and 2017. While continuing to exploit my new skills in optogenetics through a number of collaborations, I started studying how vestibulo-cerebellar Purkinje cells (the output neurons of the vestibulo-cerebellum) encode head movements, with a talented PhD student called Matthieu Tihy. Believe it or not, no one (to our knowledge) had recorded previously the activity of vestibular neurons in animals that were totally free to move, although self-motion is the situation that activates vestibular organs in 99% of our life. To track the parameters of head movements in these animals, we equipped them with small inertial sensors such as the ones found in smartphones ; these sensors measure exactly the same parameters as vestibular organs, namely head’s acceleration and angular velocity. This paradigm allowed us to show that the output of the vestibulo-cerebellum contains a fused representation of gravitational acceleration and angular velocity ; in some cases, this representation is tuned in such a way that it encodes how the head rotates about an “external” axis (defined in the Earth reference frame) [4] ; this computation might be essential for the function of downstream neuronal structures, such as the ones that encode head direction (the so-called “head direction” neurons).

I was appointed Chargé de recherche at the CNRS on October 2017, in the team of Clément Léna and Daniela Popa. My work will be focused on the cerebellar computations that transform self-generated inputs, in particular vestibular inputs, into signals that can be used for spatial orientation and navigation. I will also study vestibulo-postural functions in a mouse line exhibiting a point mutation that causes idiopathic scoliosis (IS) in humans. In parallel, I will continue to work on the development of miniature inertial sensing devices for rodents [5] ; I believe that these devices can bring behavioral studies to a new level of precision by enabling the automatic detection and scoring of a great number of behaviors in rodents. I’m convinced that knowledge is only great when it is shared, so I will remain an advocate for open science and collaboration.

Selected publications
  • Dugué GP, Dumoulin A, Triller A and Dieudonné S. Target-dependent use of co-released inhibitory transmitters at central synapses. J Neurosci. 2005 Jul 13 ;25(28):6490-8.
  • Dugué GP, Brunel N, Hakim V, Schwartz E, Chat M, Lévesque M, Courtemanche R, Léna C and Dieudonné S. Electrical coupling mediates tunable low-frequency oscillations and resonance in the cerebellar Golgi cell network. Neuron. 2009 Jan 15 ;61(1):126-39.
  • Dugué GP, Lörincz ML, Lottem E, Audero E, Matias S, Correia PA, Léna C and Mainen ZF. Optogenetic recruitment of dorsal raphe serotonergic neurons acutely decreases mechanosensory responsivity in behaving mice. PLoS One. 2014 Aug 22 ;9(8):e105941.
  • Dugué GP, Tihy M, Gourévitch B and Léna C. Cerebellar re-encoding of self-generated head movements. Elife. 2017 Jun 13 ;6. pii : e26179.
  • Pasquet MO, Tihy M, Gourgeon A, Pompili MN, Godsil BP, Léna C and Dugué GP. Wireless inertial measurement of head kinematics in freely-moving rats. Sci Rep. 2016 Oct 21 ;6:35689.