la génétique, l'imagerie calcique à deux photons chez des souris éveillées, le comportement, l'électrophysiologie et l'optogénétique.

The neocortex plays a crucial role in all cognitive functions. This is accomplished through connections between neuronal networks which emerge from synaptic interactions of many neuron types. Inhibitory interneurons constitute a sparse but crucial neuronal class which coordinate cortical activity. One of their most remarkable features is their spectacular diversity, however, a definitive classification of interneurons is still being defined. Inhibitory circuits are controlled by different neuromodulators. Among them, the neurotransmitter acetylcholine (ACh) highly controls cortical activity by signaling through two classes of ACh receptors: the ionotropic nicotinic receptors and the metabotropic muscarinic receptors. Cortical ACh signaling shapes neuronal circuit dynamics and underlies specific aspects of cognitive functions and behaviors including attention, learning, memory, perception and motivation. Thus, it is not surprising that ACh receptor gene variants are strongly linked to psychiatric disorders such as schizophrenia and neurodegenerative disorders such as Alzheimer’s disease. Evidence identified that cortical inhibitory circuits and cholinergic neurotransmission are affected in psychiatric disorders, however, the actual interplay between these two systems is unknown.

Our team uses multiscale experimental approaches, combining genetics, two-photon calcium imaging in awake mice, behavior, electrophysiology and optogenetics.

5 publications majeures au cours des 5 dernières années, incluant le Pubmed ID

Koukouli F*, Montmerle M*, Aguirre A, De Brito Van Velze M, Peixoto J, Choudhary V, Varilh M, Julio-Kalajzic F, Allene C, Mendéz P, Yann Zerlaut, Marsicano G, Schlüter O, Rebola N, Bacci A, Lourenço J. Visual-area-specific tonic modulation of GABA release by endocannabinoids sets the activity and coordination of neocortical principal neurons. Cell Reports. 2022 Aug 23;40(8):111202. PMID: 36001978. *equal contribution.

Zhang CL, Koukouli F, Allegra M, Ortiz C, Kao HL, Maskos U, Changeux JP, Schmidt-Hieber C. Inhibitory control of synaptic signals preceding locomotion in mouse frontal cortex. Cell Reports. 2021 Nov 23;37(8):10035. PMID: 34818555.

Koukouli F# and Changeux JP#. Do nicotinic receptors modulate high-order cognitive processing? Trends in Neurosciences. 2020 Aug;43(8):550-564. PMID: 32591156. # corresponding authors.

Koukouli F, Rooy M, Tziotis D, Sailor K.A, O’Neill H, Levenga J, Witte M, Nilges M, Changeux JP, Hoeffer C, Stitzel J.A, Gutkin B, DiGregorio D.A, Maskos U. Nicotine reverses hypofrontality in animal models of addiction and schizophrenia. Nature Medicine. 2017 Mar;23(3):347-354. PMID: 28112735. Koukouli F#, Rooy M, Changeux JP#, Maskos U#. Nicotinic receptors in mouse prefrontal cortex modulate ultraslow fluctuations related to conscious processing. Proc Natl Acad Sci USA (PNAS). 2016 Dec 20;113(51):14823-14828. # corresponding authors

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INSERM U1266, 102-108 rue de la santé, 75014, Paris

Team leader :
Fani Koukouli
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Key words : #Cortex #préfrontal #interneurones #récepteurs #acétylcholine #troubles #psychiatriques #cognition #Prefrontal #cortex #interneurons #acetylcholine #receptors #psychiatric #disorders