Target-specific vulnerability of excitatory synapses leads to deficits in associative memory in a model of intellectual disorder
The Journal of Neuroscience - August 2013
Xander Houbaert1*, Chun-Lei Zhang1*, Frédéric Gambino2, Marilyn Lepleux1, Melissa Deshors1,3, Elisabeth Normand3, Florian Levet4, Mariana Ramos5, Pierre Billuart5, Jamel Chelly5, Etienne Herzog1, and Yann Humeau1
1. Team Synapse in cognition, Institut interdisciplinaire de neurosciences, CNRS & Université de Bordeaux UMR5297, 33077 Bordeaux, France
2. Institut des neurosciences cellulaires et intégratives, CNRS UPR3212 & Université de Strasbourg, 67000 France
3. Pôle in vivo, Institut interdisciplinaire de neurosciences, CNRS & Université de Bordeaux, UMR5297, 33077 Bordeaux, France
4. Team Imaging the cell, Institut interdisciplinaire de neurosciences, CNRS & Université de Bordeaux UMR5297, 33077 Bordeaux, France
5. CNRS, Université Paris Descartes, INSERM, UMR8104, Institut Cochin, 75014 Paris, France
Intellectual disorders (IDs) have been regularly associated with morphological and functional deficits at glutamatergic synapses in both humans and rodents. How these synaptic deficits may lead to the variety of learning and memory deficits defining ID is still unknown.
Here we studied the functional and behavioral consequences of the ID gene il1rapl1 deficiency in mice and reported that il1rapl1 constitutive deletion alters cued fear memory formation. Combined in vivo and in vitro approaches allowed us to unveil a causal relationship between a marked inhibitory/excitatory (I/E) imbalance in dedicated amygdala neuronal subcircuits and behavioral deficits.
Cell-targeted recordings further demonstrated a morpho-functional impact of the mutation at thalamic projections contacting principal cells, whereas the same afferents on interneurons are unaffected by the lack of Il1rapl1. We thus propose that excitatory synapses have a heterogeneous vulnerability to il1rapl1 gene constitutive mutation and that alteration of a subset of excitatory synapses in neuronal circuits is sufficient to generate permanent cognitive deficits.
Yann Humeau, tel. 05 57 57 56 87
, tel. 05 57 57 57 48