RT Journal Article
SR Electronic
T1 Aggrecan Directs Extracellular Matrix-Mediated Neuronal Plasticity
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10102
OP 10113
DO 10.1523/JNEUROSCI.1122-18.2018
VO 38
IS 47
A1 Daire Rowlands
A1 Kristian K. Lensjø
A1 Tovy Dinh
A1 Sujeong Yang
A1 Melissa R. Andrews
A1 Torkel Hafting
A1 Marianne Fyhn
A1 James W. Fawcett
A1 Gunnar Dick
YR 2018
UL http://www.jneurosci.org/content/38/47/10102.abstract
AB In the adult brain, the extracellular matrix (ECM) influences recovery after injury, susceptibility to mental disorders, and is in general a strong regulator of neuronal plasticity. The proteoglycan aggrecan is a core component of the condensed ECM structures termed perineuronal nets (PNNs), and the specific role of PNNs on neural plasticity remains elusive. Here, we genetically targeted the Acan gene encoding for aggrecan using a novel animal model. This allowed for conditional and targeted loss of aggrecan in vivo, which ablated the PNN structure and caused a shift in the population of parvalbumin-expressing inhibitory interneurons toward a high plasticity state. Selective deletion of the Acan gene in the visual cortex of male adult mice reinstated juvenile ocular dominance plasticity, which was mechanistically identical to critical period plasticity. Brain-wide targeting improved object recognition memory.SIGNIFICANCE STATEMENT The study provides the first direct evidence of aggrecan as the main functional constituent and orchestrator of perineuronal nets (PNNs), and that loss of PNNs by aggrecan removal induces a permanent state of critical period-like plasticity. Loss of aggrecan ablates the PNN structure, resulting in invoked juvenile plasticity in the visual cortex and enhanced object recognition memory.