Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex.
Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown. Since hypomyelination due to isolation is prominent in deep-layer of medial PFC (mPFC), we focused on 2 types of Layer-5 pyramidal cells in the mPFC: prominent h-current (PH) cells and nonprominent h-current (non-PH) cells. We found that a 2-week social isolation after weaning leads to a specific deterioration in action potential properties and reduction in excitatory synaptic inputs in PH cells. The effects of social isolation on PH cells, which involve reduction in functional glutamatergic synapses and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate charge ratio, are specific to the 2 weeks after weaning and to the mPFC. We conclude that juvenile social experience plays crucial roles in the functional development in a subtype of Layer-5 pyramidal cells in the mPFC. Since these neurons project to subcortical structures, a deficit in social experience during the critical period may result in immature neural circuitry between mPFC and subcortical targets.
Department of Psychiatry, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Kazuhiko
K
Yamamuro
Department of Psychiatry, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Hiroki
H
Yoshino
Department of Physiology I, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Yoichi
Y
Ogawa
Department of Psychiatry, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Manabu
M
Makinodan
Department of Psychiatry, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Michihiro
M
Toritsuka
Center for Medical Science, International University of Health and Welfare, Ohtawara, Tochigi 324-8501, Japan.
Masayuki
M
Yamashita
Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Gabriel
G
Corfas
Department of Psychiatry, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Toshifumi
T
Kishimoto
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D003423:Critical Period, Psychological; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology*; D017966:Pyramidal Cells / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D012934:Social Isolation; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione
development; excitatory circuit; juvenile; social experience