Impact of Perineuronal Nets on Electrophysiology of Parvalbumin Interneurons, Principal Neurons, and Brain Oscillations: A Review

Abstract

Perineuronal nets (PNNs) are specialized extracellular matrix structures that surround specific neurons in the brain and spinal cord, appear during critical periods of development, and restrict plasticity during adulthood. Removal of PNNs can reinstate juvenile-like plasticity or, in cases of PNN removal during early developmental stages, PNN removal extends the critical plasticity period. PNNs surround mainly parvalbumin (PV)-containing, fast-spiking GABAergic interneurons in several brain regions. These inhibitory interneurons profoundly inhibit the network of surrounding neurons via their elaborate contacts with local pyramidal neurons, and they are key contributors to gamma oscillations generated across several brain regions. Among other functions, these gamma oscillations regulate plasticity associated with learning, decision making, attention, cognitive flexibility, and working memory. The detailed mechanisms by which PNN removal increases plasticity are only beginning to be understood. Here, we review the impact of PNN removal on several electrophysiological features of their underlying PV interneurons and nearby pyramidal neurons, including changes in intrinsic and synaptic membrane properties, brain oscillations, and how these changes may alter the integration of memory-related information. Additionally, we review how PNN removal affects plasticity-associated phenomena such as long-term potentiation (LTP), long-term depression (LTD), and paired-pulse ratio (PPR). The results are discussed in the context of the role of PV interneurons in circuit function and how PNN removal alters this function.

Gabaergic Interneurons in Early Brain Development: Conducting and Orchestrated by Cortical Network Activity

“…The PNN can control synaptic plasticity by preventing spine formation (Vo et al, 2013 ). In support of this, degradation of PNNs leads to reduced gamma activity in juvenile mice (Carceller et al, 2020 ), which is in line with recent discovery linking PV to gamma activity (Bitzenhofer et al, 2020 ) and the finding that altered PNNs lead to abnormal activity (Wingert and Sorg, 2021 ). In addition to the role of PNNs, other molecular mechanisms can influence PV development, such as tonic activation of NMDA receptor (Hanson et al, 2019 ), BDNF (Lau et al, 2021 ), or retinoic acid (Larsen et al, 2019 ), whose receptor expression is also dependent on activity.…”

Parvalbumin Interneurons and Perineuronal Nets in the Hippocampus and Retrosplenial Cortex of Adult Male Mice After Early Social Isolation Stress and Perinatal NMDA Receptor Antagonist Treatment

“…Because of the crucial role of PV+ interneurons have in regulating the activity of pyramidal neurons and the excitation/inhibition balance (Ferguson and Gao, 2018 ), and the influence of PNNs on their connectivity and plasticity (Testa et al, 2019 ; Wingert and Sorg, 2021 ); the alterations in PV+ and PNNs in both the RSC and the hippocampus and their impact on the connectivity of these regions deserve further studies in schizophrenic patients and animal models of the disease.…”

“…They can also interact with ion channels on the cell membrane and control synaptic plasticity by stabilizing recently formed synapses and preventing synaptogenesis (Faissner et al, 2010 ; Hayani et al, 2018 ). PNNs also regulate the inhibitory input on PV+ cells and gamma oscillations, which are dependent on these inhibitory neurons (Carceller et al, 2020 ; Wingert and Sorg, 2021 ). Interestingly PNNs are remarkably altered in the amygdala, as well as in the entorhinal and PFC of subjects diagnosed with schizophrenia (Pantazopoulos et al, 2010 ; Mauney et al, 2013 ; Markota et al, 2014 ).…”

Surfactant protein C, a modulator of paravascular brain waste clearance, is associated with perineuronal nets and shows age-dependent changes of brain content and characteristic deposits in wildtype and 3xTg mice

“…4d). While in the neocortex and numerous further brain regions WFA-binding sites surround predominantly fast-ring, parvalbumin-containing GABAergic neurons [54,55], a considerable portion of nets enwraps neurons containing other neurotransmitters [56]. Notably, net-bearing cholinergic neurons were detected in the human nucleus abducens [57] and in the rat spinal cord [58].…”