A Comprehensive Atlas of Perineuronal Net Distribution and Colocalization with Parvalbumin in the Adult Mouse Brain

Abstract

Perineuronal nets (PNNs) surround specific neurons in the brain and are involved in various forms of plasticity and clinical conditions. However, our understanding of the PNN role in these phenomena is limited by the lack of highly quantitative maps of PNN distribution and association with specific cell types. Here, we present the first comprehensive atlas of PNN distribution (in Allen Brain Atlas coordinates) and colocalization with parvalbumin (PV) cells for over 600 regions of the adult mouse brain. Data analysis showed that PV expression is a good predictor of PNN aggregation. In the cortex, PNNs are dramatically enriched in layer 4 of all primary sensory areas in correlation with thalamocortical input density, and their distribution mirrors intracortical connectivity patterns. Gene expression analysis identified many PNN correlated genes. Strikingly, PNN anticorrelated transcripts were enriched in synaptic plasticity genes, generalizing PNN role as circuit stability factors. Overall, this atlas offers novel resources for understanding the organizational principles of the brain extracellular matrix.

Perineuronal nets as regulators of parvalbumin interneuron function: Factors implicated in their formation and degradation

“…Using brain-wide analysis of the colocalization between PNNs and PV-positive cells, a recent study indicated that around 60% of WFA-labelled PNNs in the entire mouse brain are located around PV-positive cells. 6 PV interneurons are classified as fast-spiking interneurons due to their rapid repolarization and depolarization compared to other neurons. Upon Ca 2+ influx preceding a depolarization, PV quickly binds to Ca 2+ , resulting in reduced K + current and a shortened refractory period.…”

“…3 In addition, as PV expression enhances, the PNNs aggregation around these interneurons also increases. 6 The condensate and maturity composition of PNNs acts as a "molecular brake" that closes various critical periods of plasticity. 30 While aging decreases the expression of PV protein and impairs the fast-spiking properties of PV interneurons, 31 age-related changes in the density and thickness of PNNs remain controversial in the current literature.…”

“…5 The unique PNN lattice-like structures are tightly wrapped with synaptic contacts on the soma and proximal dendrites of neurons distributed in different brain regions, such as the neocortex, hippocampus, amygdala and hypothalamus. 4,6 Additionally, PNNs surround many neurons in the ventral and intermediate horns of the spinal cord, including motor neurons. 7 In the prefrontal cortex (PFC) and hippocampus, PNNs are mostly associated with inhibitory interneurons, preferentially surrounding fastspiking GABAergic interneurons containing the calcium (Ca 2+ ) binding protein parvalbumin (PV).…”

“…8 In fact, PV expression has been suggested as a good predictor of PNN aggregation. 6 However, in some brain regions, including the CA2 subregion of the hippocampus, PNNs are also found ensheathing excitatory pyramidal neurons. 9 PV interneurons are crucial for maintaining and regulating the excitatory/inhibitory (E/I) balance.…”

“…The ECM comprises approximately 20% of the brain's volume and is critical to neuron–neuron and neuron–glia interactions 5 . The unique PNN lattice‐like structures are tightly wrapped with synaptic contacts on the soma and proximal dendrites of neurons distributed in different brain regions, such as the neocortex, hippocampus, amygdala and hypothalamus 4,6 . Additionally, PNNs surround many neurons in the ventral and intermediate horns of the spinal cord, including motor neurons 7 .…”