Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning

Banerjee, Sunayana B.; Gutzeit, Vanessa A.; Baman, Justin; Aoued, Hadj; Doshi, Nandini; Liu, Robert C.; Ressler, Kerry J.

doi:10.1016/j.neuron.2017.06.007

Cited by 128 publications

(115 citation statements)

References 71 publications

(90 reference statements)

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“…We present, to our knowledge for the first time, evidence that WFA+ PNN vary according to diurnal rhythms in the human brain and to diurnal and circadian rhythms in the rodent brain. Our data adds to a growing number of studies demonstrating that PNNs are dynamic structures, responding to the environment and potentially contributing to memory consolidation during sleep (Balmer et al, 2009;Brown et al, 2009;Banerjee et al, 2017;Dingess et al, 2018;Slaker et al, 2018), We show that numbers of WFA+ PNN follow diurnal rhythms in several brain regions in mouse and in human. Importantly, we show that WFA+PNN rhythmicity occurs in mice kept in constant darkness, supporting the claim that these changes reflect circadian rhythms rather than a response to light-dark cycles (Fig.6).…”

Section: Discussionsupporting

confidence: 60%

“…PNNs are well represented in neural circuits involved in emotion processing and critically involved in the regulation of fear and reward memories (Gogolla et al, 2009;Slaker et al, 2015;Banerjee et al, 2017;Lasek et al, 2018). Consistent with these observations, PNNs have been implicated in several brain disorders involving these regions, including schizophrenia, bipolar disorder, Alzheimer's disease and addiction (Baig et al, 2005;Morawski et al, 2010;Pantazopoulos et al, 2010a;Mauney et al, 2013;Xue et al, 2014;Pantazopoulos et al, 2015;Slaker et al, 2015;Steullet et al, 2017;Blacktop and Sorg, 2018).…”

Section: Introductionmentioning

confidence: 83%

“…Our findings may also be relevant to the pathophysiology of PTSD. PNNs are strongly involved in fear memory processing, which is enhanced in this disorder (for review see/ (Parsons and Ressler, 2013) (Gogolla et al, 2009;Banerjee et al, 2017). Sleep deprivation has been proposed as an early therapeutic approach for PTSD following a traumatic experience (Kuriyama et al, 2010;Cohen et al, 2012;Cohen et al, 2017).…”

Section: Implications For Psychiatric Disordersmentioning

confidence: 99%

“…PNNs form during the end of critical periods of plasticity, marking their closure by conferring an adult form of restricted plasticity (Pizzorusso et al, 2002;Gogolla et al, 2009;Mauney et al, 2013). Although PNNs have been historically considered stable structures, recent studies suggest they are modified during learning to allow for formation of synapses (Nagy et al, 2007;Brown et al, 2009;Ganguly et al, 2013;Banerjee et al, 2017;Slaker et al, 2018). An important line of evidence comes from studies on matrix metalloproteases, which cleave ECM components including chondroitin sulfate proteoglycans (CSPGs), key components of PNNs, and contribute to regulation of synaptic plasticity (Muir et al, 2002;Porter et al, 2005;Bajor and Kaczmarek, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Circadian Rhythms of Perineuronal Net Composition

Pantazopoulos

Gisabella

Rexrode

et al. 2020

Preprint

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Perineuronal Nets (PNNs) are extracellular matrix (ECM) structures that envelop neurons and regulate synaptic functions. Long thought to be stable structures, PNNs have been recently shown to respond dynamically during learning, potentially regulating the formation of new synapses. We postulated that PNNs may vary during sleep, a period of active synaptic modification. Notably, PNN components are cleaved by matrix proteases such as the protease cathepsin-S, synthesized by microglia. Cathepsin-S is expressed in a diurnal manner in the mouse cortex, coinciding with dendritic spine density rhythms. Thus, cathepsin-S may induce PNN remodeling during sleep, mediating synaptic reorganization. These studies were designed to test the hypothesis that PNN numbers vary in a diurnal manner in the rodent and human brain, and in a circadian manner in the rodent brain, in association with cathepsin-S expression rhythms coinciding with reported rhythms in synaptic plasticity. In mice, we observed diurnal and circadian rhythms of PNNs labeled with the lectin wisteria floribunda agglutinin (WFA+PNNs) in several brain regions involved in emotional memory processing. Sleep deprivation prevented the daytime decrease of WFA+ PNNs. Diurnal rhythms of cathepsin-S expression in microglia were observed in the same brain regions, opposite to PNN rhythms. Finally, incubation of mouse sections with cathepsin-S eliminated PNN labeling. In humans, WFA+PNNs showed a diurnal rhythm in the amygdala and thalamic reticular nucleus (TRN). Our results demonstrate that PNNs vary in a circadian manner that coincides with expression rhythms of cathepsin-S in the mouse hippocampus. We suggest that rhythmic modification of PNNs may contribute to memory consolidation during sleep.

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Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 83%

Section: Implications For Psychiatric Disordersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circadian Rhythms of Perineuronal Net Composition

Pantazopoulos

Gisabella

Rexrode

et al. 2020

Preprint

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“…Sorg et al, 2016;Ueno et al, 2019). Experiments involving the enzymatic removal of PNN by chondroitinase ABC (ChABC) or hyaluronidase injections in amygdala, hippocampus, piriform and auditory cortices have shown that synaptic plasticity can be reactivated (Banerjee et al, 2017;Gogolla et al, 2009;Kochlamazashvili et al, 2010;Krishnan, Lau et al, 2017;Pizzorusso et al, 2002;Thompson et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Lateralized expression of cortical perineuronal nets during maternal experience is dependent on MECP2

Lau

Layo

Emery

et al. 2019

Preprint

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Cortical neuronal circuits along the sensorimotor pathways are shaped by experience during critical periods of heightened plasticity in early postnatal development. After closure of critical periods, measured histologically by the formation and maintenance of extracellular matrix structures called perineuronal nets (PNNs), the adult mouse brain exhibits restricted plasticity and maturity. Mature PNNs are typically considered to be stable structures that restrict synaptic plasticity on cortical parvalbumin+ GABAergic neurons. Changes in environment (i.e. novel behavioral training) or social contexts (i.e. motherhood) are known to elicit synaptic plasticity in relevant neural circuitry. However, little is known about concomitant changes in the PNNs surrounding the cortical parvalbumin+ GABAergic neurons. Here, we show novel changes in PNN density in the primary somatosensory cortex (SS1) of adult female mice after maternal experience, using systematic microscopy analysis of a whole brain region. On average, PNNs were increased in the right barrel field and decreased in the left forelimb regions. Individual mice had left hemisphere dominance in PNN density. Using adult female mice deficient in methyl-CpG-binding protein 2 (MECP2), an epigenetic regulator involved in regulating experience-dependent plasticity, we found that MECP2 is critical for this precise and dynamic expression of PNN. Adult naïve Mecp2-heterozygous females (Het) had increased PNN density in specific subregions in both hemispheres before maternal experience. The laterality in PNN expression seen in naïve Het was lost after maternal experience, suggesting possible intact mechanisms for plasticity. Together, our results identify subregion and hemisphere-specific alterations in PNN expression in adult females, suggesting extracellular matrix plasticity as a possible neurobiological mechanism for adult behaviors in rodents.

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Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury

Shi

Cui

et al. 2022

Advanced Science

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Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD). Augmented fear is a defining characteristic of PTSD, and the amygdala is considered the main brain region to process fear. The mechanism by which the amygdala is involved in fear conditioning after TBI is still unclear. Using single‐nucleus RNA sequencing (snRNA‐seq), transcriptional changes in cells in the amygdala after TBI are investigated. In total, 72 328 nuclei are obtained from the sham and TBI groups. 7 cell types, and analysis of differentially expressed genes (DEGs) reveals widespread transcriptional changes in each cell type after TBI are identified. In in vivo experiments, it is demonstrated that Decorin (Dcn) expression in the excitatory neurons of the amygdala significantly increased after TBI, and Dcn knockout in the amygdala mitigates TBI‐associated fear conditioning. Of note, this effect is caused by a Dcn‐mediated decrease in the expression of perineuronal nets (PNNs), which affect the glutamate‐γ‐aminobutyric acid balance in the amygdala. Finally, the results suggest that Dcn functions by interacting with collagen VI α3 (Col6a3). Consequently, the findings reveal transcriptional changes in different cell types of the amygdala after TBI and provide direct evidence that Dcn relieves fear conditioning by regulating PNNs.

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Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning

Cited by 128 publications

References 71 publications

Circadian Rhythms of Perineuronal Net Composition

Circadian Rhythms of Perineuronal Net Composition

Lateralized expression of cortical perineuronal nets during maternal experience is dependent on MECP2

Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury

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