Sebastian H. Bitzenhofer,1,2,3,∗ Jastyn A. Pöpplau,1,2 Mattia Chini,1 Annette Marquardt,1 and Ileana L. Hanganu-Opatz1,4,∗∗
1Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Sebastian H. Bitzenhofer: ude.dscu@refohneztibs; Ileana L. Hanganu-Opatz: ed.grubmah-inu.hnmz@pognah
∗Corresponding author ude.dscu@refohneztibs
∗∗Corresponding author ed.grubmah-inu.hnmz@pognah
2These authors contributed equally
3Present address: Center for Neural Circuits and Behavior, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
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.
Square light stimuli of 473 nm or 585 nm wavelength and 10 ms or 1 s duration were delivered with the pE-2 LED system (CoolLED, Andover, UK).
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CoolLED LED Illumination Systems are ideal for optogenetic stimulation with the ability to perform precise pulsing at different durations.
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