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Hippocampus. 2018 Jan;28(1):42-52. doi: 10.1002/hipo.22804. Epub 2017 Sep 26.

Disruption of perineuronal nets increases the frequency of sharp wave ripple events.

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Jilin Women and Children's Health Hospital, Changchun, Jilin, China.
Department of Neuroscience, Georgetown University School of Medicine, Washington, District of Columbia.
Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, District of Columbia.
Department of Pharmacology, Georgetown University School of Medicine, Washington, District of Columbia.
Applied Physics Laboratory, Johns Hopkins University, Baltimore, Maryland.


Hippocampal sharp wave ripples (SWRs) represent irregularly occurring synchronous neuronal population events that are observed during phases of rest and slow wave sleep. SWR activity that follows learning involves sequential replay of training-associated neuronal assemblies and is critical for systems level memory consolidation. SWRs are initiated by CA2 or CA3 pyramidal cells (PCs) and require initial excitation of CA1 PCs as well as participation of parvalbumin (PV) expressing fast spiking (FS) inhibitory interneurons. These interneurons are relatively unique in that they represent the major neuronal cell type known to be surrounded by perineuronal nets (PNNs), lattice like structures composed of a hyaluronin backbone that surround the cell soma and proximal dendrites. Though the function of the PNN is not completely understood, previous studies suggest it may serve to localize glutamatergic input to synaptic contacts and thus influence the activity of ensheathed cells. Noting that FS PV interneurons impact the activity of PCs thought to initiate SWRs, and that their activity is critical to ripple expression, we examine the effects of PNN integrity on SWR activity in the hippocampus. Extracellular recordings from the stratum radiatum of horizontal murine hippocampal hemisections demonstrate SWRs that occur spontaneously in CA1. As compared with vehicle, pre-treatment (120 min) of paired hemislices with hyaluronidase, which cleaves the hyaluronin backbone of the PNN, decreases PNN integrity and increases SWR frequency. Pre-treatment with chondroitinase, which cleaves PNN side chains, also increases SWR frequency. Together, these data contribute to an emerging appreciation of extracellular matrix as a regulator of neuronal plasticity and suggest that one function of mature perineuronal nets could be to modulate the frequency of SWR events.


PV interneuron; chondrotinase; hippocampus; hyaluronidase; protease

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