Romain Goutagny’s home-page
I’m a neuroscientist with a specialization in in-vivo electrophysiology. I am fascinated by brain oscillations, their dynamic and their role in cognitive functions (and dysfunctions). I’m carrying out interdisciplinary research combining behavioral testing, large scale electrophysiological recording and circuit manipulation using optogenetic and/or DREADD. My research try to elucidate how complex brain oscillatory dynamic (from hippocampal recordings to large scale EEG recordings) shape information processing in brain networks in normal and pathological conditions (Alzheimer’s disease…).
A few research ideas
Hippocampal theta rhythm is crucial for spatial memory and is thought to be generated by extrinsic inputs. In contrast, we found that CA1 theta rhythm can emerge from the coupling of multiple autonomous hippocampal theta oscillators.
Alzheimer’s disease (AD) is a neurodegenerative pathology commonly characterized by a progressive and irreversible deterioration of cognitive functions, especially memory. Even though the etiology of AD remains unknown, a consensus has emerged on the amyloid hypothesis which posits that increased production of soluble amyloid beta peptide (Aβ) induces neuronal network dysfunctions and cognitive deficits. However, the relative failures of Aβ-centric therapeutics suggest that the amyloid hypothesis is incomplete and/or that the treatment were given too late in the course of AD, when neuronal damages were already too extensive. Using an animal model of AD, we showed that some of the early memory deficits are Aβ independent. Our results could partly explain the limited efficacy of Aβ-directed treatments and favor multi-therapy approaches for early symptomatic treatment for AD.
Currently, curative treatment trials for Alzheimer Disease have failed. The endogenous ability of the brain to cope with neuronal loss probably represents one of the most promising therapeutic targets, but underlying mechanisms are still undetermined. Here we show that the mammalian brain is able to manage the deleterious consequences of the loss of entorhinal neurons on both hippocampal activity and cognitive performance, first through a fast cholinergic sprouting followed by a slower glutamatergic reinnervation. The cholinergic sprouting is gender-dependent and highly sensitive to the genetic risk factor APOE4. Our findings highlight the specific impact of early loss of entorhinal input on hippocampal hyperactivity and cognitive deficits characterizing early stages of Alzheimer’s disease, especially in APOE4 carriers.
Brain oscillatory activity is critical for cognitive function and is altered in AD patients. Recent evidence suggests that accumulation of soluble amyloid-beta (Aβ) induces reorganization of hippocampal networks. However, whether fine changes in network activity might be present at very early stages, before Aβ overproduction, remains to be determined. We were able to show that initial alterations in hippocampal network activity (theta-gamma coupling) arise before Aβ accumulation and may represent an early biomarker for AD.
2015 HDR in Neuroscience (Strasbourg, France)
2006 PhD in Neuroscience (Lyon, France; with Pierre-Hervé Luppi & Patrice Fort)
2002 Master in Neuroscience (Lyon, France)
Since 2011 CNRS Research faculty at the Laboratory for Cognitive and Adaptive Neuroscience (LNCA UMR 7364; Strasbourg University)
2006–2011 Postdoc in Sylvain Williams lab, McGill University, Montréal, Québec, Canada
2017 Prix scientifique « Les espoirs de l’Université de Strasbourg 2017 ».
2011 NARSAD young investigator award.
2010 McGill Medstar award, McGill faculty of medicine, Montréal, QC, Canada.
2009 «aide au retour» award from the French society for neuroscience, Bordeaux, France.
Five selected publications
- Hamm V, Héraud C, Bott JB, Herbeaux K, Strittmatter C, Mathis C, Goutagny R (2017). Differential contribution of APP metabolites to early cognitive deficits in TgCRND8 mouse model of Alzheimer’s disease. Sci Adv. 2017 Feb 24;3(2):e1601068. doi: 10.1126/sciadv.1601068. This study was the first showing that other APP metabolites than amyloid-beta peptide can have deleterious effect on memory performances in a young mouse model of AD
- Bott JB, Héraud C, Cosquer B, Herbeaux K, Aubert J, Sartori M, Goutagny R*, Mathis C* (2016). APOE-Sensitive Cholinergic Sprouting Compensates for Hippocampal Dysfunctions Due to Reduced Entorhinal Input. J Neurosci.36(40):10472-10486. *: Equal contributors. doi: 10.1523/JNEUROSCI.1174-16.2016. This study showed for the first time that the APOE-4 genotype is a risk factor for AD by preventing cholinergic sprouting and associated memory improvement following partial entorhinal lesion
- Bott JB, Muller MA, Jackson J, Aubert J, Cassel JC, Mathis C, Goutagny R (2016). Spatial Reference Memory is Associated with Modulation of Theta-Gamma Coupling in the Dentate Gyrus. Cereb Cortex. 26(9):3744-53. doi: 10.1093/cercor/bhv177. This study was the first one showing the dynamic of theta-gamma coupling in dentate gyrus network during the learning of a spatial task
- Jackson J, Amilhon B, Goutagny R, Bott JB, Manseau F, Kortleven C, Bressler SL, Williams S (2014). Reversal of theta rhythm flow through intact hippocampal circuits. Nat Neurosci. 17(10):1362-70. doi: 10.1038/nn.3803. In this study, we showed for the first time that, within hippocampal networks, information can flow backward, from the subiculum to CA3 (and not necessarily following the classical tri-synaptic loop)
- Goutagny R*, Jackson J*, Williams S (2009). Self-generated theta oscillations in the hippocampus. Nat Neurosci. 2009 Dec;12(12):1491-3. *: Equal contributors. doi: 10.1038/nn.2440. Here we showed for the firsts time that the hippocampus possesses the whole network sufficient and necessary to generate theta oscillations on its own (without the need of an external pacemaker like the medial septum).
Romain’s news and science
In our newest preprint on BioRxiv, in collaboration with Alessandro Torcini and Matteo di Volo, we revisit a classic theory about the existence of two different gamma rhythms in the hippocampus CA1. We first deconstruct this theory, showing its insufficiency to account for the haphazard diversity of hippocampal gamma. We however reconstruct and rescue the…
Alzheimer’s disease (AD) is a neurodegenerative pathology commonly characterized by a progressive and irreversible deterioration of cognitive functions, especially memory. Although the etiology of AD remains unknown, a consensus has emerged on the amyloid hypothesis, which posits that increased production of soluble amyloid b (Ab) peptide induces neuronal network dysfunctions and cognitive deficits. In our…
Spatial reference memory in rodents represents a unique opportunity to study brain mechanisms responsible for encoding, storage and retrieval of a memory. Even though its reliance on hippocampal networks has long been established, the precise computations performed by different hippocampal subfields during spatial learning are still not clear. In our Cerebral Cortex paper, to study…
Hippocampal theta rhythm is crucial for spatial memory and is thought to be generated by extrinsic inputs. In our Nature Neuroscience paper, though, we show that, using a complete rat hippocampus in vitro, several intrinsic, atropine-resistant theta generators can be found directly in CA1. These oscillators were organized along the septotemporal axis and arose independently…
How to find us
We are located within the building of the Faculty of Psychology, at the ground floor (LNCA wing, to the right, end of the corridor, entering from Rue Goethe side).
LNCA – 12 rue Goethe, F-67000 STRASBOURG
Tramway lines C/E/F – stop « Université » – Bus line 2 (~15 min from central station) – Strasbourg Entzheim airport at ~40 min, high speed train to Paris CDG and Frankfurt / Main international hubs.