Team Koukouli

Cholinergic modulation of cortical inhibitory circuits in health and disease


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. 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.

 

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5 Main Publications:

Koukouli F, Montmerle M, Aguirre A, De Brito Van Velze M, Peixoto J, Choudhary V, Varilh M, Julio-Kalajzic F, Allene C, Mendéz P, Zerlaut Y, Marsicano G, Schlüter OM, 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 Rep. 2022 Aug 23;40(8):111202. doi: 10.1016/j.celrep.2022.111202. 

 

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 Rep. 2021 Nov 23;37(8):110035. doi: 10.1016/j.celrep.2021.110035. 

 

Koukouli F, Changeux JP. Do Nicotinic Receptors Modulate High-Order Cognitive Processing?. Trends Neurosci. 2020 Aug;43(8):550-564. doi: 10.1016/j.tins.2020.06.001. Epub 2020 Jun 23. Review. 

 

Koukouli F, Rooy M, Tziotis D, Sailor KA, O'Neill HC, Levenga J, Witte M, Nilges M, Changeux JP, Hoeffer CA, Stitzel JA, Gutkin BS, DiGregorio DA, Maskos U. Nicotine reverses hypofrontality in animal models of addiction and schizophrenia. Nat Med. 2017 Mar;23(3):347-354. doi: 10.1038/nm.4274. Epub 2017 Jan 23. 

 

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 U S A. 2016 Dec 20;113(51):14823-14828. doi: 10.1073/pnas.1614417113. Epub 2016 Dec 2.