Abstract
The prefrontal-hippocampal dysfunction that underlies cognitive deficits in mental disorders emerges during early development. The contribution of the lateral entorhinal cortex (LEC), a gatekeeper of prefrontal cortex (PFC) and hippocampus (HP), to the early dysfunction is fully unknown. Here we show that the poorer LEC-dependent associative recognition memory detectable at pre-juvenile age is preceded by abnormal communication within LEC-HP-PFC networks of neonatal mice mimicking the combined genetic and environmental etiology (GE) of disease. The prominent entorhinal drive to HP is weaker in GE mice as a result of sparser projections from LEC to CA1 and decreased efficiency of axonal terminals to activate the hippocampal circuits. In contrast, the direct entorhinal drive to PFC is not affected in GE mice, yet the PFC is indirectly compromised, as target of the under-activated HP. Thus, already at neonatal age, the entorhinal function gating prefrontal-hippocampal circuits is impaired in a mouse model of disease.
Faculty Opinions recommendation of Imaging patients with psychosis and a mouse model establishes a spreading pattern of hippocampal dysfunction and implicates glutamate as a driver.