Layer-specific impairment in the developing lateral entorhinal cortex of immune-challenged Disc1+/- mice.

Cognitive deficits in mental disorders result from dysfunctional activity in large-scale brain networks centred around the hippocampus and the prefrontal cortex. Dysfunctional activity emerges early during development and precedes the cognitive disabilities. The prefrontal-hippocampal network is driven by a prominent input from the lateral entorhinal cortex. We have previously shown that during early development, the entorhinal drive of the prefrontal-hippocampal network is impaired in a mouse model of mental disorders, yet the cellular substrate of this impairment is still poorly understood. Here, we address this question by a detailed characterization of projection neurons across the layers of the lateral entorhinal cortex in immune-challenged Disc1+/- mice at the beginning of the second postnatal week. We found that the activity and morphology of neurons in layers 2b and 3, which project to the hippocampus, are impaired. Neurons in layer 2b show increased spike-frequency adaptation, whereas neurons in layer 3 have reduced dendritic complexity but increased spike density. These findings identify the developmental alterations of entorhinal-hippocampal communication that underlie network dysfunction in immune-challenged Disc1+/- mice. KEY POINTS: Neonatal immune-challenged Disc1+/- mice show layer-specific changes in the lateral entorhinal cortex. Entorhinal layer 2b pyramidal neurons have increased spike-frequency adaptation. Reduced dendritic complexity but increased spine density characterize layer 3 pyramidal neurons.