Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican

Favuzzi, Emilia; Marques-Smith, André; Deogracias, Rubén; Winterflood, Christian M.; Sánchez-Aguilera, Alberto; Mantoan, Laura; Maeso, Patricia; Fernandes, Cathy; Ewers, Helge; Rico, Beatriz

doi:10.1016/j.neuron.2017.06.028

Cited by 313 publications

(339 citation statements)

References 53 publications

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“…In this study, we observe that the frequency of SWR events is increased in hippocampal slices that are pretreated with proteases known to disrupt integrity of the PNN (Bikbaev et al, ). This suggests that PNN disruption is sufficient not only to reduce glutamatergic input to individual PV cells as previously described (Favuzzi et al, ), but to affect the dynamics of large‐scale population events initiated by hippocampal PCs. Since PV FSIs represent the predominant cell type known to be ensheathed by a PNN (Pantazopoulos and Berretta, ), PNN digestion likely affects PC excitability through modulation of inhibitory input from the PV population.…”

Section: Discussionsupporting

confidence: 70%

“…Glutamate receptors on PV interneurons are localized to soma and proximal dendrites, both of which are typically ensheathed by PNN (Favuzzi et al, ). Of interest, the subpopulation of PV cells that is rich in PNN, as determined by staining with the CSPG brevican, receives relatively robust glutamatergic input (Favuzzi et al, ). With PNN disruption released glutamate may more easily diffuse.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Similarly, genetic deletion of the PNN component brevican has been associated with altered intrinsic properties and reduced synaptic input to PV interneurons through changes in potassium channel localization and levels of GluAs (Favuzzi et al . ). Of interest, antidepressants including venlafaxine have been linked to an increased risk of seizures and disinhibition could contribute to the same.…”

Section: Discussionmentioning

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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“…In addition, TnR ablation impairs spatial and motor learning 58 . Similarly, loss of brevican disrupts long-term potentiation 59 , and results in memory deficits 60 . Together, the downregulation in the expression of several synaptic ECM proteins shortly after social defeat may result in ECM composition-dependent aberrant synaptic transmission that could contribute to the observed memory deficits.…”

Section: Figure 5 Schematic Of the Main Conclusion: Ecm Imbalance Comentioning

confidence: 99%

“…Although the precise mechanisms by which PNNs regulate the activity of PV +interneurons remains elusive, PNNs have been shown to modulate the excitability and highfrequency firing of PV + -interneurons 61,62 . Recently, it was shown that mainly Brevican that is expressed by PV + -interneurons controls PV-excitability via the modulation of excitatory inputs these neurons receive, and controls molecular components of synaptic and intrinsic plasticity 60 . Conversely, hippocampus-dependent learning, and intrinsic plasticity affect activity of PV +interneurons and Brevican levels 63,60 .…”

Section: Figure 5 Schematic Of the Main Conclusion: Ecm Imbalance Comentioning

confidence: 99%

From stress to depression: Development of extracellular matrix-dependent cognitive impairment following social stress

Koskinen

Mourik

Smit

et al. 2019

Preprint

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Stress can predispose to depressive episodes, yet the molecular mechanisms regulating the transition from the initial stress response to a persistent pathological depressive state remain poorly understood. To shed light on this stress-to-depression transition process, we profiled the development of an enduring depressive-like state in rat by assessing affective behavior and hippocampal function during the 2 months following social defeat stress. In addition, we measured remodeling of hippocampal extracellular matrix (ECM) during this period, as we recently identified ECM changes to mediate cognitive impairment during a sustained depressivelike state. We found affective disturbance and cognitive impairment to develop disparately after social stress. While affective deficits emerged gradually, spatial memory impairment was present both early after stress and during the late-emerging chronic depressive-like state. Surprisingly, these phases were separated by a period of normalized hippocampal function. Similarly, the SDPS paradigm induced a biphasic regulation of the hippocampal ECM coinciding with hippocampus-dependent memory deficits. Early after stress, synaptic ECM proteins and the number of perineuronal nets enwrapping parvalbumin-expressing interneurons were decreased. This was followed by a recovery period without ECM dysregulation, before subsequent decreased metalloproteinase activity and ECM build-up, previously shown to impair memory. This suggests that intact hippocampal function requires unaltered ECM levels. Together our data 1) reveal a dichotomy between affective and cognitive impairments similar to that observed in patients, 2) indicate different molecular processes taking place during early stress and the chronic depressive-like state, and 3) support a role of the ECM in mediating long-lasting memoryeffects of social stress.

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Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican

Cited by 313 publications

References 53 publications

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

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

From stress to depression: Development of extracellular matrix-dependent cognitive impairment following social stress

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