Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
- University Medical Center Hamburg-Eppendorf
Published 22 Oct. 2021 | License Creative Commons CC0 1.0 Public Domain Dedication
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.
Keywords| Neuroscience | LEC | DISC1 |
- Xiaxia Xu, Lingzhen Song, Rebecca Kringel et al. Developmental decrease of entorhinal gate disrupts prefrontal-hippocampal communication in immune-challenged DISC1 knockdown mice, 10 March 2021, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-290304/v1]
- DFG SFB 936 B5 and Ha4466/11-1 to I.L.H.-O
- EU ERC-2015-CoG 681577 to I.L.H.-O.