Experience-Dependent Structural Plasticity of Adult-Born Neurons in the Aging Hippocampus

TRINCHERO, MARIELA F.; HERRERO, MAGALÍ; MONZÓN-SALINAS, M. CRISTINA; SCHINDER, ALEJANDRO F.

Frontiers in Neuroscience

Frontiers

Año: 2019 vol. 13

Synaptic modification in cortical structures underlies the acquisition of novel informationthat results in learning and memory formation. In the adult dentate gyrus, circuitremodeling is boosted by the generation of new granule cells (GCs) that contributeto specific aspects of memory encoding. These forms of plasticity decrease in theaging brain, where both the rate of adult neurogenesis and the speed of morphologicalmaturation of newly generated neurons decline. In the young-adult brain, a briefnovel experience accelerates the integration of new neurons. The extent to whichsuch degree of plasticity is preserved in the aging hippocampus remains unclear. Inthis work, we characterized the time course of functional integration of adult-bornGCs in middle-aged mice. We performed whole-cell recordings in developing GCsfrom Ascl1CreERT2;CAGfloxStopTom mice and found a late onset of functional excitatorysynaptogenesis, which occurred at 4 weeks (vs. 2 weeks in young-adult mice). Overallmature excitability and maximal glutamatergic connectivity were achieved at 10 weeks.In contrast, large mossy fiber boutons (MFBs) in CA3 displayed mature morphologicalfeatures including filopodial extensions at 4 weeks, suggesting that efferent connectivitydevelops faster than afference. Notably, new GCs from middle-aged mice exposed toenriched environment for 7 days showed an advanced degree of maturity at 3 weeks,revealed by the high frequency of excitatory postsynaptic responses, complex dendritictrees, and large size of MFBs with filopodial extensions. These findings demonstrate thatadult-born neurons act as sensors that transduce behavioral stimuli into major networkremodeling in the aging brain.