Background and Purpose: The locus coeruleus (LC) produces the majority of brain noradrenaline (NA). Among its many roles, NA has a protective role for cells in the central nervous system. Loss of LC integrity is, therefore, thought to cause alterations to brain volume and microstructure, possibly driving the development of neurodegenerative diseases. Experimental Approach: Ablation effect is ascertained by behaviour analysis prior to ex vivo investigations. We use high-field magnetic resonance imaging (MRI) to investigate brain volumetrics and microstructure in control (CON) mice and mice with LC ablation (LCA) at two ages. Our study employs whole-brain methods known to be capable of detecting subtle morphological changes and brain microstructural remodelling. Key Results: Mice show behaviour consistent with histologically confirmed LC ablation. However, MRI shows no difference between CON and LCA groups with regard to brain size, relative regional volumes, or regional microstructural indices. Conclusion and Implications: Our study suggests that LC-NA is not needed for postnatal brain maturation and growth in mice. Nor is it required for maintenance in the normal, adult mouse brain. This adds clarity to the often-encountered notion that LC-NA is important for brain ”trophic support” as it shows that such effects are likely most relevant to mechanisms related to brain plasticity and neuroprotection.

Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here we investigated the role of postnatal immune activation on hippocampal synaptopathology by targeting Reelin+ cells in mice with ASD-like behavior. C57/Bl6 mouse pups of both sexes received lipopolysaccharide (LPS, 1mg/kg) on postnatal day (P) 5. At P45, animal behavior was examined by marble burying and sociability test, followed by ex-vivo brain MRI diffusion kurtosis imaging (DKI). Hippocampal synaptogenesis, number and morphology of Reelin+ cells, and mRNA expression of trans-synaptic genes, including neurexin-3, neuroligin-1, and cell-adhesion molecule nectin-1 were analyzed at P12 and P45. Social withdrawal and increased stereotypic activities in males were related to increased mean diffusivity on MRI-DKI and overgrowth in hippocampus together with retention of long-thin immature synapses on apical dendrites, decreased volume and number of Reelin+ cells as well as reduced expression of trans-synaptic and cell-adhesion molecules. The study provides new insights into sex-dependent mechanisms that may underlie ASD-like behavior in males following PIA. We identify GABAergic interneurons as core components of dysmaturation of excitatory synapses in the hippocampus following postnatal infection and provide cellular and molecular substrates for the MRI findings with translational value.