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Cereb Cortex. 2016 Oct 17;26(11):4265-4281. doi: 10.1093/cercor/bhw274.

From Shortage to Surge: A Developmental Switch in Hippocampal-Prefrontal Coupling in a Gene-Environment Model of Neuropsychiatric Disorders.

Author information

1
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
2
Laboratory of Neurobiology, Department of Biosciences, University of Helsinki, 00014 Helsinki, Finland.
3
Laboratory of Neural Computation, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, 38068 Rovereto, Italy.
4
Current address: German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.
5
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
6
Department of Neuroscience, Columbia University, New York, NY 10032, USA.
7
Department of Physiology, Columbia University, New York, NY 10032, USA.

Abstract

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.

KEYWORDS:

development; network oscillations; prefrontal cortex; schizophrenia; synchrony

PMID:
27613435
PMCID:
PMC5066837
DOI:
10.1093/cercor/bhw274
[Indexed for MEDLINE]
Free PMC Article

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