The Dehorter Group - Neuronal Development

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 the 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.

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Ahmed NY, Knowles R, Liu L, Yan Y, Li X, Schumann U, Wang Y, Sontani Y, Reynolds N, Natoli R, Wen J, Del Pino I, Mi D, Dehorter N. Developmental deficits of MGE-derived interneurons in the Cntnap2 knockout mouse model of autism spectrum disorder. Front Cell Dev Biol. 2023 Feb 1;11:1112062. doi: 10.3389/fcell.2023.1112062. PMID: 36819097; PMCID: PMC9930104.

Al Abed SA, Reynolds NJ, Dehorter N. A Second Wave for the Neurokinin Tac2 Pathway in Brain Research.  Biological Psychiatry 2021 Feb doi:10.1016/j.biopsych.2021.02.016

Al Abed SA, Sellami A, Marighetto A, Desmedt A, Dehorter N. Autism Spectrum Disorder is a Risk Factor for PTSD-like Memory Formation BioRxiv. 2021 Jan. doi: 10.1101/2021.01.18.427217

Dehorter N & Del Pino I. Shifting Developmental Trajectories During Critical Periods of Brain Formation.  Front Cell Neurosci. 2020 Sep 10;14:283. doi: 10.3389/fncel.2020.00283. eCollection 2020. PMID: 33132842 Free PMC article. Review.

Ranjbar-Slamloo Y, Ahmed NY, Al Abed SA, Gao L, Sontani Y, R’Com-H Cheo A, Arabzadeh A, Dehorter N. Loss of the Er81 Transcription Factor in Cholinergic Cells Alters Striatal Activity and Habit Formation BioRxiv. 2020 Jan. doi:10.1101/2020.01.14.905497

Ahmed NY, Knowles R, Dehorter N. New Insights Into Cholinergic Neuron Diversity.  Front Mol Neurosci. 2019 Aug 27;12:204. doi: 10.3389/fnmol.2019.00204. eCollection 2019. PMID: 31551706 Free PMC article. Review.

Scott R, Sánchez-Aguilera A, van Elst K, Lim L, Dehorter N, Bae SE, Bartolini G, Peles E, Kas MJH, Bruining H, Marín O. Loss of Cntnap2 Causes Axonal Excitability Deficits, Developmental Delay in Cortical Myelination, and Abnormal Stereotyped Motor Behavior. Cereb Cortex. 2019 Feb 1;29(2):586-597. doi: 10.1093/cercor/bhx341. PMID: 29300891

Dehorter N, Marichal N, Marín O, Berninger B. Tuning neural circuits by turning the interneuron knob.  Curr Opin Neurobiol. 2017 Feb;42:144-151. doi: 10.1016/j.conb.2016.12.009. Epub 2017 Jan 11. PMID: 28088067 Review.

Dehorter N, Ciceri G, Bartolini G, Lim L, del Pino I, Marín O. Tuning of fast-spiking interneuron properties by an activity-dependent transcriptional switch.  Science. 2015 Sep 11;349(6253):1216-20. doi: 10.1126/science.aab3415. PMID: 26359400

Ciceri G, Dehorter N. [Organization of interneurons lineages in the cerebral cortex].  Med Sci (Paris). 2014 Feb;30(2):144-6. doi: 10.1051/medsci/20143002010. Epub 2014 Feb 24. PMID: 24572111 Free article. French. No abstract available.

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. Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes.  Neuron. 2013 Sep 18;79(6):1152-68. doi: 10.1016/j.neuron.2013.07.010. PMID: 24050403

Ciceri G, Dehorter N, Sols I, Huang ZJ, Maravall M, Marín O. Lineage-specific laminar organization of cortical GABAergic interneurons.  Nat Neurosci. 2013 Sep;16(9):1199-210. doi: 10.1038/nn.3485. Epub 2013 Aug 11. PMID: 23933753

Dehorter N, Lozovaya N, Mdzomba BJ, Michel FJ, Lopez C, Tsintsadze V, Tsintsadze T, Klinkenberg M, Gispert S, Auburger G, Hammond C.Subthalamic lesion or levodopa treatment rescues giant GABAergic currents of PINK1-deficient striatum. J Neurosci. 2012 Dec 12;32(50):18047-53. doi: 10.1523/JNEUROSCI.2474-12.2012. PMID: 23238720

Dehorter N, Vinay L, Hammond C, Ben-Ari Y. Timing of developmental sequences in different brain structures: physiological and pathological implications.  Eur J Neurosci. 2012 Jun;35(12):1846-56. doi: 10.1111/j.1460-9568.2012.08152.x. PMID: 22708595 Review.

Ferrari DC, Mdzomba BJ, Dehorter N, Lopez C, Michel FJ, Libersat F, Hammond C. Midbrain dopaminergic neurons generate calcium and sodium currents and release dopamine in the striatum of pups.  Front Cell Neurosci. 2012 Mar 8;6:7. doi: 10.3389/fncel.2012.00007. eCollection 2012. PMID: 22408606

Dehorter N, Michel FJ, Marissal T, Rotrou Y, Matrot B, Lopez C, Humphries MD, Hammond C. Onset of Pup Locomotion Coincides with Loss of NR2C/D-Mediated Cortico-Striatal EPSCs and Dampening of Striatal Network Immature Activity.  Front Cell Neurosci. 2011 Nov 21;5:24. doi: 10.3389/fncel.2011.00024. eCollection 2011. PMID: 22125512

Gelman D, Griveau A, Dehorter N, Teissier A, Varela C, Pla R, Pierani A, Marín O. J A wide diversity of cortical GABAergic interneurons derives from the embryonic preoptic area. Neurosci. 2011 Nov 16;31(46):16570-80. doi: 10.1523/JNEUROSCI.4068-11.2011. PMID: 22090484

Dehorter N, Guigoni C, Lopez C, Hirsch J, Eusebio A, Ben-Ari Y, Hammond C. Dopamine-deprived striatal GABAergic interneurons burst and generate repetitive gigantic IPSCs in medium spiny neurons.  J Neurosci. 2009 Jun 17;29(24):7776-87. doi: 10.1523/JNEUROSCI.1527-09.2009. PMID: 19535589

Bouvier J, Autran S, Dehorter N, Katz DM, Champagnat J, Fortin G, Thoby-Brisson M. Brain-derived neurotrophic factor enhances fetal respiratory rhythm frequency in the mouse preBötzinger complex in vitro. Eur J Neurosci. 2008 Aug;28(3):510-20. doi: 10.1111/j.1460-9568.2008.06345.x. PMID: 18702723