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Published on: May 12, 2015
Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
Xiaxia Xu1, Lingzhen Song2, Rebecca Kringel2
1Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany. xiaxia.xu@zmnh.uni-hamburg.de.
Insights
Early-life psychiatric risk impairs recognition memory and brain network communication in mice. This dysfunction stems from underdeveloped connections between the lateral entorhinal cortex and hippocampus during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Psychiatry
Background:
- Cognitive deficits in mental disorders are linked to prefrontal-hippocampal dysfunction.
- The lateral entorhinal cortex (LEC) connects the prefrontal cortex (PFC) and hippocampus (HP), but its role in early developmental dysfunction is unclear.
Purpose of the Study:
- To investigate the contribution of the lateral entorhinal cortex to early-life cognitive deficits in a mouse model of psychiatric risk.
Main Methods:
- Utilized a mouse model (GE mice) mimicking dual genetic and environmental etiology of psychiatric risk.
- Assessed recognition memory and neural network communication at pre-juvenile stages.
- Examined projections and synaptic function between LEC, HP, and PFC.
Main Results:
- GE mice exhibited poor LEC-dependent recognition memory and abnormal LEC-HP-PFC network communication.
- Neonatal GE mice showed sparser LEC to CA1 projections and reduced axonal terminal efficiency.
- Direct LEC to PFC connections were unaffected, but PFC was indirectly compromised via the HP.
Conclusions:
- The entorhinal-hippocampal circuit is impaired from neonatal stages in mice with psychiatric risk factors.
- Early-life dysfunction in the LEC-HP-PFC network contributes to cognitive deficits.
- This highlights the critical role of early development in shaping neural circuits relevant to mental disorders.
Abstract:
The prefrontal-hippocampal dysfunction that underlies cognitive deficits in mental disorders emerges during early development. The lateral entorhinal cortex (LEC) is tightly interconnected with both prefrontal cortex (PFC) and hippocampus (HP), yet its contribution to the early dysfunction is fully unknown. Here we show that mice that mimic the dual genetic (G) -environmental (E) etiology (GE mice) of psychiatric risk have poor LEC-dependent recognition memory at pre-juvenile age and abnormal communication within LEC-HP-PFC networks throughout development. These functional and behavioral deficits relate to sparser projections from LEC to CA1 and decreased efficiency of axonal terminals to activate the hippocampal circuits in neonatal GE mice. In contrast, the direct entorhinal drive to PFC is not affected, yet the PFC is indirectly compromised, as target of the under-activated HP. Thus, the entorhinal-hippocampal circuit is already impaired from neonatal age on in GE mice.
