The Dehorter Group aims to determine how interneurons shape neuronal networks activity and contribute to circuits balance in health and disease. While early genetic specification seems to drive the cardinal properties of the interneurons, it is increasingly recognized that their final features are subject to regulation by experience. We seek to identify genetic programs triggered by neuronal activity that lead to the remarkable diversity of neuronal subclasses.
We want to address fundamental questions:
- How do interneurons adapt their activity to environment and transmit appropriate information to the rest of the neuronal circuit?
- How these adaptive processes shape emergent networks and modulate inhibitory circuits in normal condition and in pathology?
- Can we detect early signs of interneuron dysfunction in pathologies such as Parkinson’s disease, schizophrenia or autism and restore normal activity to alleviate or block consequent deleterious symptoms?
To achieve our goals, we will take advantage of a multi-disciplinary approach, employing state of the art molecular biology, genetics, in vitro/ in vivo imaging and electrophysiological techniques.
Key words: Interneurons, transcription factors, activity-dependent plasticity, development, neurological disorders.
THE DEHORTER GROUP IS CURRENTLY ACCEPTING APPLICATIONS FOR HONOURS AND PHD PROJECTS.
To express interest of enquire please contact firstname.lastname@example.org
Research projects available for Honours Students:
These projects include histological characterization (immunohistochemistry and western blot), in vitro patch-clamp recordings and behavioural studies during development in control and mutant mice.
(1) Role of a transcription factor involved in cell identity and function.
(2) Developmental expression and role of a receptor involved in schizophrenia.
(3) Early signs of impaired neuronal activity in a mouse model of striatum-related pathology.
Research projects for PhD students:
These projects will study fundamental scientific concepts and will require the use of state-of-the-art multidisciplinary techniques.
(1) To understand the function of a receptor in interneuron identity and plasticity.
Electrophysiology (in vitro patch-clamp recordings), viral infections, opto-genetics, 2-photon calcium imaging and behaviour.
(2) To study the consequences of an impaired neuronal activity during development in a mouse model of autism.
Viral infections, opto- and pharmaco-genetic approaches and Electrophysiology (in vitro and in vivo recordings).
Tuning neural circuits by turning the interneuron knob. Dehorter N, Marichal N, Marín O, Berninger B. Curr Opin Neurobiol. 2017 Jan 11;42:144-151. doi: 10.1016/j.conb.2016.12.009
Tuning of Fast Spiking Interneuron properties by an Activity-Dependent Transcriptional Switch. Dehorter N, Ciceri G, Bartolini G, Lim L, Del Pino I, Marin O. Science. 2015 Sep 11;349(6253):1216-20.
Giant GABAA receptor mediated currents in the striatum, a common signature of Parkinson's disease in pharmacological and genetic rodent models. Dehorter N, Hammond C. Basal Ganglia Journal , 2014 April;3(4) :197–20
Organization of interneurons lineages in the cerebral cortex. Ciceri G*, Dehorter N*. Med Sci (Paris). 2014 Feb;30(2):144-6. (*co-authors)
Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes. Del Pino I*, García-Frigola C*, Dehorter N^, Brotons-Mas JR^, Alvarez-Salvado E, Martínez de Lagrán M, Ciceri G, Gabaldón MV, Moratal D, Dierssen M, Canals S, Marín O, Rico B. Neuron. 2013 Sep 18;79(6):1152-68. (*first co-authors; ^ second co-authors)
Lineage-specific laminar organization of cortical GABAergic interneurons. Ciceri G, Dehorter N, Sols I, Huang ZJ, Maravall M, Marín O. Nat Neurosci. 2013 Sep;16(9):1199-210.
Subthalamic lesion or levodopa treatment rescues giant GABAergic currents of PINK1-deficient striatum. Dehorter N, Lozovaya N, Mdzomba BJ, Michel FJ, Lopez C, Tsintsadze V, Tsintsadze T, Klinkenberg M, Gispert S, Auburger G, Hammond C. J Neurosci. 2012 Dec 12;32(50):18047-53.
Timing of developmental sequences in different brain structures: physiological and pathological implications. Dehorter N, Vinay L, Hammond C, Ben-Ari Y. Eur J Neurosci. 2012 Jun;35(12):1846-56.
Midbrain dopaminergic neurons generate calcium and sodium currents and release dopamine in the striatum of pups. Ferrari DC, Mdzomba BJ, Dehorter N, Lopez C, Michel FJ, Libersat F, Hammond C. Front Cell Neurosci. 2012 Mar 8;6:7.
Onset of Pup Locomotion Coincides with Loss of NR2C/D-Mediated Cortico-Striatal EPSCs and Dampening of Striatal Network Immature Activity. Dehorter N, Michel FJ, Marissal T, Rotrou Y, Matrot B, Lopez C, Humphries MD, Hammond C. Front Cell Neurosci. 2011 Nov 21
A wide diversity of cortical GABAergic interneurons derives from the embryonic preoptic area. Gelman D*, Griveau A*, Dehorter N*, Teissier A, Varela C, Pla R, Pierani A, Marín O. J Neurosci. 2011 Nov 16; 31(46):16570-80. (*first co-authors)
Dopamine-deprived striatal GABAergic interneurons burst and generate repetitive gigantic IPSCs in medium spiny neurons. Dehorter N, Guigoni C, Lopez C, Hirsch J, Eusebio A, Ben-Ari Y, Hammond C. J Neurosci. 2009 Jun 17;29(24):7776-87.
Brain-derived neurotrophic factor enhances fetal respiratory rhythm frequency in the mouse preBötzinger complex in vitro. Bouvier J, Autran S, Dehorter N, Katz DM, Champagnat J, Fortin G, Thoby-Brisson M. Eur J Neurosci. 2008 Aug;28(3):510-20.