High plasticity of new granule cells in the aging hippocampus

TRINCHERO MF; HERRERO M; SULKES CUEVAS, JN; TEMPRANA SG; FONTANET P; MONZÓN-SALINAS, M. CRISTINA; LEDDA MF; PARATCHA, GUSTAVO; SCHINDER AF

Dresden

Congreso; Adult Neurogenesis Conference; 2018

Abcam

The aging brain displays a generalized decline in cognitive capacity and circuit plasticity, including a marked decrease in production of adult-born hippocampal neurons. It is unclear whether development and integration of those new neurons are also affected by age. In this work we show that adult-born granule cells (GCs) in aging mice are scarce and exhibit slow development, but they display a remarkable potential for structural plasticity. Retrovirally labeled three-week-old GCs in middle-aged mice were small, underdeveloped and disconnected. Voluntary exercise induced substantial dendritic growth and the formation of functional glutamatergic inputs. The effects of aging were also attenuated byknockdown of Lrig1, an endogenous negative modulator of neurotrophin receptor signaling. Moreover the acceleration of neuronal development exerted by running was blocked by overexpression of Lrig1 highlighting neurotrophin signaling as a key player in the mechanism of neuronal plasticity in the aging brain.