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.

Keywords: memory; oscillations; parvalbumin; perineuronal nets (PNNs); plasticity.

Figure 1

(A) List of perineuronal net (PNN) removal-mediated changes in parvalbumin (PV) interneuron intrinsic properties that one-third or more of the experiments agreed upon (see Supplementary Table 1 for a complete list of studies). (B) Graphical representation from table shown in (A) of changes in PV interneuron intrinsic properties following PNN removal. (C) Experimentally agreed upon firing rate changes to PV interneurons following PNN removal, indicating deficits in firing rate at high stimulation levels. Created with BioRender.com.

Figure 2

Hippocampal long-term potentiation (LTP) in the CA1 following Schaffer collateral stimulation was altered in six of the seven studies following PNN removal [see Supplementary Table 3 for a complete list of LTP/long-term depression (LTD) and paired-pulse ratio (PPR) studies]. (A) With PNNs intact, Schaffer collateral stimulation induces LTP. (B) With PNNs removed, Schaffer collateral stimulation-induced LTP is impaired. Created with BioRender.com.

Figure 3

Circuit state following PV interneuron dysfunction after PNN removal. Neural assemblies originally representing a stimulus or memory may overlap when exposed to a similar stimulus or memory if PNNs are removed between the first and second exposure. Summary is based on PV interneuron specific manipulations and circuit functions (see “Role of PV Interneurons in Pattern Separation and Sparse Encoding” section). Created with BioRender.com.