GABA-A receptor-dependent mechanisms prevent excessive spine elimination during postnatal maturation of the mouse cortex in vivo

Dendritic spine dynamics are implicated in the structural plasticity of cognition-related neuroconnectivity. This study utilized the transcranial in vivo imaging approach to investigate spine dynamics in intact brains of living yellow fluorescent protein-expressing mice. A developmental switch in the net spine loss rate occurred at ∼4 months of age. The initially rapid rate slowed down ∼6-fold due to substantially reduced spine elimination with minor changes in formation. Furthermore, pharmacological blockade of γ-aminobutyric acid type A (GABA-A) receptors resulted in significantly increased elimination of pre-existing spines without affecting new spine formation. Spine elimination returned to normal levels following treatment cessation. Thus, GABA-A receptor-dependent mechanisms act as “brakes” – keeping spine elimination in check to prevent over-pruning, thereby preserving the integrity of cognition-related cortical circuits.     

Changes in lamina propria dendritic cells on the oral administration of exogenous protein antigens during weaning

Two critical periods of maximum exposure to antigens occur in young mammals, immediately after birth and at weaning, as a result of colonization by commensal bacteria and the ingestion of new diets. At weaning, active immune responses of antibody production against dietary proteins are known to occur, but simultaneously, oral tolerance is acquired for harmless food proteins. However, regulated mechanisms of the immune system at weaning remain to be elucidated although its immune responses may be somewhat similar to those in adulthood. Considering that tolerogenic antigen-presenting cells (APCs) are likely to be a key factor in the acquisition of oral tolerance, in the present study, we examined the changes of dendritic cells (DCs) in the lamina propria (LP) on exposure to food proteins at weaning. C57BL/6 female mice were weaned at the age of 3 weeks and orally administered 10 mg of ovalbumin (OVA) for ten consecutive days after weaning. The administration led to a decrease in the plasma level of immunoglobulin specific for OVA, suggesting the acquisition of oral tolerance. The uptake of fluorescence-labeled OVA was significantly observed for CD11c⁺LPDCs. When we analyzed the changes of two types of LPDCs, PDCA-1⁺ MHC II⁺ DCs and CD103⁺ MHC II⁺ DCs, ten consecutive gavages of OVA marginally, but not significantly, augmented only the frequency of PDCA-1⁺ MHC II⁺ DCs. Considering that the change of APCs likely appears immediately on the response to antigen intake, we found the statistically significant increase in the frequency of PDCA-1⁺ DCs, but not in that of CD103⁺ DCs, even after two treatments, indicating PDCA-1⁺ DCs to be recruited in the LP within 2 days of exposure to food proteins. These results suggest that the behavior of tolerogenic PDCA-1⁺ DCs may change at weaning with the removal of the immunoprotective components of maternal milk.