From Shortage to Surge: A Developmental Switch in Hippocampal-Prefrontal Coupling in a Gene-Environment Model of Neuropsychiatric Disorders.
Cognitive deficits represent a major burden of neuropsychiatric disorders and result in part from abnormal communication within hippocampal-prefrontal circuits. While it has been hypothesized that this network dysfunction arises during development, long before the first clinical symptoms, experimental evidence is still missing. Here, we show that pre-juvenile mice mimicking genetic and environmental risk factors of disease (dual-hit GE mice) have poorer recognition memory that correlates with augmented coupling by synchrony and stronger directed interactions between prefrontal cortex and hippocampus. The network dysfunction emerges already during neonatal development, yet it initially consists in a diminished hippocampal theta drive and consequently, a weaker and disorganized entrainment of local prefrontal circuits in discontinuous oscillatory activity in dual-hit GE mice when compared with controls. Thus, impaired maturation of functional communication within hippocampal-prefrontal networks switching from hypo- to hyper-coupling may represent a mechanism underlying the pathophysiology of cognitive deficits in neuropsychiatric disorders.
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.|Laboratory of Neurobiology, Department of Biosciences, University of Helsinki, 00014 Helsinki, Finland.
Henrike
H
Hartung
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Nicole
N
Cichon
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.|Laboratory of Neural Computation, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, 38068 Rovereto, Italy.
Vito
V
De Feo
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.|Current address: German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.
Stephanie
S
Riemann
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Sandra
S
Schildt
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Christoph
C
Lindemann
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Christoph
C
Mulert
Department of Neuroscience, Columbia University, New York, NY 10032, USA.|Department of Physiology, Columbia University, New York, NY 10032, USA.
Joseph A
JA
Gogos
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Ileana L
IL
Hanganu-Opatz
D000818:Animals; D000831:Animals, Newborn; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002658:Developmental Disabilities / Q000139:chemically induced / Q000150:complications / Q000235:genetics; D004195:Disease Models, Animal; D005071:Evoked Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007369:Interferon Inducers / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D011070:Poly I-C / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology
C498794:Disc1 protein, mouse; D007369:Interferon Inducers; D009419:Nerve Tissue Proteins; D011070:Poly I-C
development; network oscillations; prefrontal cortex; schizophrenia; synchrony