A critical period for experience-dependent plasticity in neurons born in the aged hippocampus

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

Congreso; Congreso anual de la Sociedad Argentina de Investigación en Neurociencia; 2019

The aging brain displays a generalized decline in cognitive capacity and circuit plasticity, including a decline in the production of adult-born hippocampal neurons. Morphological development of new dentate granule cells (GCs) is also affected by age. However, their functional properties and integration to the circuit along maturation remains unclear. We performed whole-cell recordings in 8-month old (8M) Ascl1(CreERT2);CAG(floxStopTom) mice to assess intrinsic properties, firing behavior and afferent excitatory connectivity in adult-born GCs labeled with tdTomato. We found that functional properties and connectivity of these neurons develop very slowly. Despite the delayed maturation, new GCs in aging mice display a remarkable potential for structural plasticity. Retrovirally labeled 3-week-old GCs in middle-aged mice are small, underdeveloped and disconnected. Notably, we found that a 7-day exposure to an enriched environment (EE) induced substantial dendritic growth, spine formation and increase in the number of filopodia of mossy fiber boutons in CA3, indicating that experience boosts both input and output connectivity. EE was particularly effective in promoting integration during the second week of GCs development, but not earlier or later. Moreover, EE accelerated maturation of intrinsic membrane properties and functional integration of new GCs. This short period of increased responsiveness to hippocampal activity induced by experience unveils high levels of plasticity of newborn GCs in the aging hippocampus.