Differential Expression and Cell-Type Specificity of Perineuronal Nets in Hippocampus, Medial Entorhinal Cortex, and Visual Cortex Examined in the Rat and Mouse

Lensjø, Kristian Kinden; Christensen, Ane Charlotte; Tennøe, Simen; Fyhn, Marianne; Hafting, Torkel

doi:10.1523/eneuro.0379-16.2017

Cited by 95 publications

(100 citation statements)

References 88 publications

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“…The Ca2+/calmodulin‐dependent protein kinase II (CAMKII) antibody recognized a band of approximately 50 kDa (predicted molecular weight: 56 kDa) on Western blots of mouse brain tissue lysate (manufacturer's datasheet), and stained a pattern of cellular morphology (somata of pyramidal neurons) and distribution in the mouse cerebral cortex that was identical with previous reports (Castillo‐Gómez et al, ; Lensjø, Christensen, Tennøe, Fyhn, & Hafting, ).…”

Section: Methodssupporting

confidence: 84%

Dark exposure affects plasticity‐related molecules and interneurons throughout the visual system during adulthood

Carceller

Guirado

Nácher

2019

J of Comparative Neurology

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Several experimental manipulations, including visual deprivation, are able to induce critical period‐like plasticity in the visual cortex of adult animals. In this regard, many studies have analyzed the effects of dark exposure in adult animals, but still little is known about the role of interneurons and plasticity‐related molecules on such mechanisms. In this study, we analyzed the effects of 10 days of dark exposure on the connectivity and structure of interneurons, both in the primary visual cortex and in the rest of cerebral regions implicated in the transmission of visual stimulus. We found that this environmental manipulation induces changes in the expression of synaptic molecules throughout the visual pathway and in the structure of interneurons in the primary visual cortex. Moreover, we found altered expression in the polysialylated form of the neural cell adhesion molecule and in perineuronal nets surrounding parvalbumin expressing interneurons, suggesting that these plasticity‐related molecules may be involved in the changes produced by dark exposure. Together, our findings indicate that dark exposure produces an important alteration of inhibitory circuits and molecules related to their plasticity, not only in the visual cortex but throughout the visual pathway.

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Section: Methodssupporting

confidence: 84%

Dark exposure affects plasticity‐related molecules and interneurons throughout the visual system during adulthood

Carceller

Guirado

Nácher

2019

J of Comparative Neurology

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“…This suggests that PNN disruption is sufficient not only to reduce glutamatergic (Slaker et al, 2015). A recent study also suggests loss of the PNN can decrease inhibition in the visual cortex (Lensjo, Lepperod, Dick, Hafting, & Fyhn, 2017b), an area with an abundance of PNN enwrapped PV expressing neurons (Lensjo, Christensen, Tennoe, Fyhn, & Hafting, 2017a). Of particular interest, this was associated with an increase in gamma frequency activity FIG URE 2 Horizontal slice preparation and staining.…”

Section: Discussionmentioning

confidence: 94%

“…This possibility is supported by studies showing reduced excitability of PV cells, and a reduction in the frequency of inhibitory currents in PCs, following enzyme‐mediated cleavage of PNNs (Slaker et al, ). A recent study also suggests loss of the PNN can decrease inhibition in the visual cortex (Lensjo, Lepperod, Dick, Hafting, & Fyhn, ), an area with an abundance of PNN enwrapped PV expressing neurons (Lensjo, Christensen, Tennoe, Fyhn, & Hafting, ). Of particular interest, this was associated with an increase in gamma frequency activity (Lensjo et al, ).…”

Section: Discussionmentioning

confidence: 96%

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

et al. 2017

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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. K E Y W O R D Schondrotinase, hippocampus, hyaluronidase, protease, PV interneuron

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“…At approximately 4 weeks of age, a time at which PNN and/or PNN component deposition is complete in varied brain regions including hippocampus (Lensjo et al . ; Noguchi et al . ), mice were treated for 2 weeks with saline or saline containing 30 mg/kg venlafaxine.…”

Section: Methodsmentioning

confidence: 99%

“…; Lensjo et al . ). The PNN facilitates properly localized glutamatergic input to PV cells (Frischknecht et al .…”

mentioning

confidence: 97%

Venlafaxine stimulates PNN proteolysis and MMP‐9‐dependent enhancement of gamma power; relevance to antidepressant efficacy

Alaiyed

Bozzelli

Caccavano

et al. 2019

Journal of Neurochemistry

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Drugs that target monoaminergic transmission represent a first‐line treatment for major depression. Though a full understanding of the mechanisms that underlie antidepressant efficacy is lacking, evidence supports a role for enhanced excitatory transmission. This can occur through two non‐mutually exclusive mechanisms. The first involves increased function of excitatory neurons through relatively direct mechanisms such as enhanced dendritic arborization. Another mechanism involves reduced inhibitory function, which occurs with the rapid antidepressant ketamine. Consistent with this, GABAergic interneuron‐mediated cortical inhibition is linked to reduced gamma oscillatory power, a rhythm also diminished in depression. Remission of depressive symptoms correlates with restoration of gamma power. As a result of strong excitatory input, reliable GABA release, and fast firing, PV‐expressing neurons (PV neurons) represent critical pacemakers for synchronous oscillations. PV neurons also represent the predominant GABAergic population enveloped by perineuronal nets (PNNs), lattice‐like structures that localize glutamatergic input. Disruption of PNNs reduces PV excitability and enhances gamma activity. Studies suggest that monoamine reuptake inhibitors reduce integrity of the PNN. Mechanisms by which these inhibitors reduce PNN integrity, however, remain largely unexplored. A better understanding of these issues might encourage development of therapeutics that best up‐regulate PNN‐modulating proteases. We observe that the serotonin/norepinephrine reuptake inhibitor venlafaxine increases hippocampal matrix metalloproteinase (MMP)‐9 levels as determined by ELISA and concomitantly reduces PNN integrity in murine hippocampus as determined by analysis of sections following their staining with a fluorescent PNN‐binding lectin. Moreover, venlafaxine‐treated mice (30 mg/kg/day) show an increase in carbachol‐induced gamma power in ex vivo hippocampal slices as determined by local field potential recording and Matlab analyses. Studies with mice deficient in matrix metalloproteinase 9 (MMP‐9), a protease linked to PNN disruption in other settings, suggest that MMP‐9 contributes to venlafaxine‐enhanced gamma power. In conclusion, our results support the possibility that MMP‐9 activity contributes to antidepressant efficacy through effects on the PNN that may in turn enhance neuronal population dynamics involved in mood and/or memory. Cover Image for this issue: doi: .

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Differential Expression and Cell-Type Specificity of Perineuronal Nets in Hippocampus, Medial Entorhinal Cortex, and Visual Cortex Examined in the Rat and Mouse

Abstract: Visual Abstract

Cited by 95 publications

References 88 publications

Dark exposure affects plasticity‐related molecules and interneurons throughout the visual system during adulthood

Dark exposure affects plasticity‐related molecules and interneurons throughout the visual system during adulthood

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

Venlafaxine stimulates PNN proteolysis and MMP‐9‐dependent enhancement of gamma power; relevance to antidepressant efficacy

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