Abstract
The juvenile brain presents plasticity. Oligodendrocytes are the myelinating cells of the central nervous system and myelination can be adaptive. Plasticity decreases from juvenile to adulthood. The mechanisms involving oligodendrocytes underlying plasticity are unclear. Here, we show Na+-K+-Cl– co-transporter 1 (NKCC1), highly expressed in the juvenile mouse brain, regulates the oligodendrocyte activity from juvenile to adulthood in mice, as shown by optogenetic manipulation of oligodendrocytes. The reduced neuronal activity in adults was restored by Nkcc1 overexpression in oligodendrocytes. Moreover, in adult mice overexpressing Nkcc1, long-term potentiation and learning were facilitated compared to age-matched controls. These findings demonstrate that NKCC1 plays a regulatory role in the age-dependent activity of oligodendrocytes, furthermore inducing activation of NKCC1 in oligodendrocytes can restore neuronal plasticity in the adult mouse brain.
Highlights
IntroductionIn adult mice overexpressing Nkcc[1], long-term potentiation and learning were facilitated compared to agematched controls
Immunohistochemistry with the myelin marker proteolipid protein (PLP) demonstrated that myelination was initiated at approximately postnatal day (PND) 10 and reached a peak at PND 21 in the white matter of the mouse hippocampus (Fig. 1b)
DM20 was expressed by LncOL1-positive cells (Supplementary Fig. 2a), indicating that newly formed OLs are equivalent to premyelinating OLs
Summary
In adult mice overexpressing Nkcc[1], long-term potentiation and learning were facilitated compared to agematched controls These findings demonstrate that NKCC1 plays a regulatory role in the agedependent activity of oligodendrocytes, inducing activation of NKCC1 in oligodendrocytes can restore neuronal plasticity in the adult mouse brain. We find that the magnitude of axonal plastic changes induced by optogeneticmediated OL depolarization is larger in juvenile than adult mice and is related to Nkcc[1] expression and its activity in OLs. Nkcc[1] overexpression in adult mice or its knockdown in juvenile mice facilitates or suppresses the induction of myelinated fiber plasticity-related long-term potentiation (LTP), respectively. Hippocampal-dependent learning is enhanced in Nkcc1-overexpressing compared to age-matched control mice These results demonstrate that NKCC1 activity accounts for agedependent myelinated fiber plasticity and that the rejuvenation of OLs mediated by NKCC1 facilitates neural function in the adult brain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
