[en] Disturbed neuronal activity in neuropsychiatric pathologies emerges during development and might cause multifold neuronal dysfunction by interfering with apoptosis, dendritic growth, and synapse formation. However, how altered electrical activity early in life affects neuronal function and behavior in adults is unknown. Here, we address this question by transiently increasing the coordinated activity of layer 2/3 pyramidal neurons in the medial prefrontal cortex of neonatal mice and monitoring long-term functional and behavioral consequences. We show that increased activity during early development causes premature maturation of pyramidal neurons and affects interneuronal density. Consequently, altered inhibitory feedback by fast-spiking interneurons and excitation/inhibition imbalance in prefrontal circuits of young adults result in weaker evoked synchronization of gamma frequency. These structural and functional changes ultimately lead to poorer mnemonic and social abilities. Thus, prefrontal activity during early development actively controls the cognitive performance of adults and might be critical for cognitive symptoms in neuropsychiatric diseases.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Bitzenhofer, Sebastian H ; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. Electronic address: sbitzenhofer@ucsd.edu
Pöpplau, Jastyn A; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Chini, Mattia ; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Marquardt, Annette; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Hanganu-Opatz, Ileana L; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. Electronic address: hangop@zmnh.uni-hamburg.de
Language :
English
Title :
A transient developmental increase in prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice.
DFG - German Research Foundation EGU - European Geosciences Union
Funding text :
We thank Drs. T. Oertner and S. Wiegert for providing optogenetic tools; Dr. X. Xu for help with hippocampal injections; M. Hnida for help with early stimulation; and P. Putthoff, A. Dahlmann, and K. Titze for excellent technical assistance. This work was funded by grants from the European Research Council (ERC-2015-CoG 681577 to I.L.H.-O.) and the German Research Foundation (Ha 4466/10-1, Ha4466/11-1, Ha4466/12-1, SPP 1665, and SFB 936 B5 to I.L.H.-O.). S.H.B. J.A.P. and I.L.H.-O. designed the experiments. S.H.B. J.A.P. M.C. and A.M. carried out the experiments. S.H.B. J.A.P. and M.C. analyzed the data. S.H.B. J.A.P. M.C. and I.L.H.-O. interpreted the data and wrote the manuscript. All authors discussed and commented on the manuscript. The authors declare no competing interests.We thank Drs. T. Oertner and S. Wiegert for providing optogenetic tools; Dr. X. Xu for help with hippocampal injections; M. Hnida for help with early stimulation; and P. Putthoff, A. Dahlmann, and K. Titze for excellent technical assistance. This work was funded by grants from the European Research Council ( ERC-2015-CoG 681577 to I.L.H.-O.) and the German Research Foundation ( Ha 4466/10-1 , Ha4466/11-1 , Ha4466/12-1 , SPP 1665 , and SFB 936 B5 to I.L.H.-O.).
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