Limbic Npy1r affects perineuronal net structure in the limbic system

Brain plasticity is a key feature that allows the CNS to adapt to environmental stimuli, resulting in the modulation of brain circuits. Early life environment, including maternal care received, has a long-lasting impact for anxiety and stress response in adulthood. However, little is known about the effects of maternal environment on plasticity related structures in the brain regions involved in central drive of hypothalamus-pituitary-adrenal (HPA) axis activity and stress susceptibility. We have recently demonstrated that limbic Y1 receptors (Y1Rs) for Neuropeptide Y (NPY) are key targets of maternal care-induced programming of anxiety and energy homeostasis. Early life intense maternal care, such as high arched-back nursing (ABN), upregulates limbic Npy1r, whereby inducing long lasting consequences on NPY/Y1R mediated behavioral and metabolic functions. As a result, conditional inactivation of Npy1r gene in limbic excitatory neurons in Npy1rrfb mice led to increased anxiety level and HPA axis activity and lower body weight gain which become apparent only in male mice having experienced high ABN. Here we used the same conditional system to investigate the role of Y1Rs in maternal care-induced changes of brain plasticity in the limbic system. Plasticity related markers were analysed in the hippocampus and in the prefrontal cortex of Npy1rrfb conditional mutants and their control littermates (Npy1r2lox ) fostered to dams exhibiting high (FVB/6J) or low levels (C57BL6/J) of maternal care. Conditional inactivation of limbic Npy1r failed to affect the expression of BDNF, a neurotrophin with neuroproliferative and neuroprotective properties. Conversely, the intensity of perineuronal nets (PNN), aggregates of extracellular matrix molecules formed around neurons that are thought to stabilize neuronal functions at the closure of critical periods, were strongly decreased in the prelimbic cortex and in the CA1 of FVB/J-reared Npy1rrfb mice as compared to their control littermates. No differences in intensity were observed between Npy1r2lox and Npy1rrfb mice fostered to C57BL/6J dams. Significantly, control mice reared by C57BL/6J dams showed lower PNN intensity than FVB/J-fostered controls. These data suggest that conditional inactivation of the Npy1r gene in excitatory neurons led to decreased levels of plasticity in the adult limbic system which depend on early maternal conditions.