These findings rectify long-standing models that misattribute closure of the critical period to PNNs and identify that aggrecan expressed by excitatory neurons resident in the surrounding neuropil limits visual plasticity.
Abstract
Perineuronal nets (PNNs) are widely reported to close developmental critical periods and restrict experience-dependent plasticity. Here we tested this model by selectively eliminating gene expression for aggrecan (Acan), an essential component of PNNs. In visual cortex, PNNs predominantly ensheath parvalbumin-positive (PV+) interneurons. Deletion of Acan in inhibitory neurons eliminated PNNs but did not prevent closure of the critical period. By comparison, deletion of Acan in all neurons, or only in excitatory forebrain neurons, sustained critical-period plasticity in adult mice. Visual plasticity in adults was associated with reduced cortical excitatory synaptic inputs onto layer 2/3 PV+ interneurons and increased expression of some immediate early genes in visual cortex but normal response strength and tuning properties of layer 2/3 excitatory neurons. These findings rectify long-standing models that misattribute closure of the critical period to PNNs and identify that aggrecan expressed by excitatory neurons resident in the surrounding neuropil limits visual plasticity.
These findings identify Dlx5/6 as regulators of adult PV interneuron stability, linking extracellular matrix homeostasis to synaptic organization and cortical network dynamics, and provides a new mechanistic framework connecting Dlx5/6 function to PV-related pathological phenotypes, including neuropsychiatric disorders...
It is indicated that PV interneurons are most likely to have PNNs in layers 5/6 of the prelimbic cortex, but species differences suggest caution in designing and interpreting experiments that manipulate PNNs, particularly when generalizing between rat and mouse models.
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In the mature brain, the extracellular matrix (ECM) molecules derived from neurons and glia accumulate in spatially distinct extracellular compartments, including a diffuse interstitial matrix and condensed perineuronal nets (PNNs), where they regulate receptor mobility, ion homeostasis, cell-surface signaling, structu...
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S. Murase, Daniel Severin, Andrew Pranger et al.· bioRxiv· 0 citations
Early-life adversity alters inhibitory circuit maturation across developing brain systems, but most studies have focused on corticolimbic regions involved in emotional and cognitive regulation. Whether early adversity also reshapes inhibitory extracellular matrix architecture in primary sensory cortex remains less clea...
Xiao-Yi Zhan, Jing-Yu Miao, Philip Chu et al.· Neuroscience Letters· 0 citations
An input-specific translatome screen is designed to identify regulators of experience-dependent PV IN plasticity genes (XPGs) in the CA3/CA2 subregion of adult hippocampus and shows that experience-dependent PV IN plasticity is a convergent mechanism for NDD risk genes that can be re-instated in adulthood to reverse de...
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