Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.
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ABSTRACT:
SUBMITTER: Venturino A
PROVIDER: S-EPMC8284881 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The perineuronal net (PNN) region of the brain's extracellular matrix (ECM) surrounds the neural networks within the brain tissue. The PNN is a protective net-like structure regulating neuronal activity such as neurotransmission, charge balance, and action potential generation. Shock-induced damage of this essential component may lead to neuronal cell death and neurodegenerations. The shock generated during a vehicle accident, fall, or improvised device explosion may produce sufficient energy to damage the structure of the PNN. The goal is to investigate the mechanics of the PNN in reaction to shock loading and to understand the mechanical properties of different PNN components such as glycan, GAG, and protein. In this study, we evaluated the mechanical strength of PNN molecules and the interfacial strength between the PNN components. Afterward, we assessed the PNN molecules' damage efficiency under various conditions such as shock speed, preexisting bubble, and boundary conditions. The secondary structure altercation of the protein molecules of the PNN was analyzed to evaluate damage intensity under varying shock speeds. At a higher shock speed, damage intensity is more elevated, and hyaluronan (glycan molecule) is most likely to break at the rigid junction. The primary structure of the protein molecules is least likely to fail. Instead, the molecules' secondary bonds will be altered. Our study suggests that the number of hydrogen bonds during the shock wave propagation is reduced, which leads to the change in protein conformations and damage within the PNN structure. As such, we found a direct connection between shock wave intensity and PNN damage.
| S-EPMC8774183 | biostudies-literature
Project description:Grid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, in concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested that PNNs stabilize synaptic connections and long-term memories, but their role in the grid cell network remains elusive. We show that removal of PNNs leads to lower inhibitory spiking activity, and reduces grid cells' ability to create stable representations of a novel environment. Furthermore, in animals with disrupted PNNs, exposure to a novel arena corrupted the spatiotemporal relationships within grid cell modules, and the stored representations of a familiar arena. Finally, we show that PNN removal in entorhinal cortex distorted spatial representations in downstream hippocampal neurons. Together this work suggests that PNNs provide a key stabilizing element for the grid cell network.
| S-EPMC7801665 | biostudies-literature
Project description:A hallmark of schizophrenia pathophysiology is the dysfunction of cortical inhibitory GABA neurons expressing parvalbumin, which are essential for coordinating neuronal synchrony during various sensory and cognitive tasks. The high metabolic requirements of these fast-spiking cells may render them susceptible to redox dysregulation and oxidative stress. Using mice carrying a genetic redox imbalance, we demonstrate that extracellular perineuronal nets, which constitute a specialized polyanionic matrix enwrapping most of these interneurons as they mature, play a critical role in the protection against oxidative stress. These nets limit the effect of genetically impaired antioxidant systems and/or excessive reactive oxygen species produced by severe environmental insults. We observe an inverse relationship between the robustness of the perineuronal nets around parvalbumin cells and the degree of intracellular oxidative stress they display. Enzymatic degradation of the perineuronal nets renders mature parvalbumin cells and fast rhythmic neuronal synchrony more susceptible to oxidative stress. In parallel, parvalbumin cells enwrapped with mature perineuronal nets are better protected than immature parvalbumin cells surrounded by less-condensed perineuronal nets. Although the perineuronal nets act as a protective shield, they are also themselves sensitive to excess oxidative stress. The protection might therefore reflect a balance between the oxidative burden on perineuronal net degradation and the capacity of the system to maintain the nets. Abnormal perineuronal nets, as observed in the postmortem patient brain, may thus underlie the vulnerability and functional impairment of pivotal inhibitory circuits in schizophrenia.
| S-EPMC3670388 | biostudies-other
Project description:Perineuronal nets (PNNs) are specialized complexes of extracellular matrix molecules that surround the somata of fast-spiking neurons throughout the vertebrate brain. PNNs are particularly prevalent throughout the auditory brainstem, which transmits signals with high speed and precision. It is unknown whether PNNs contribute to the fast-spiking ability of the neurons they surround. Whole-cell recordings were made from medial nucleus of the trapezoid body (MNTB) principal neurons in acute brain slices from postnatal day 21 (P21) to P27 mice. PNNs were degraded by incubating slices in chondroitinase ABC (ChABC) and were compared to slices that were treated with a control enzyme (penicillinase). ChABC treatment did not affect the ability of MNTB neurons to fire at up to 1000 Hz when driven by current pulses. However, f-I (frequency-intensity) curves constructed by injecting Gaussian white noise currents superimposed on DC current steps showed that ChABC treatment reduced the gain of spike output. An increase in spike threshold may have contributed to this effect, which is consistent with the observation that spikes in ChABC-treated cells were delayed relative to control-treated cells. In addition, parvalbumin-expressing fast-spiking cortical neurons in >P70 slices that were treated with ChABC also had reduced excitability and gain. The development of PNNs around somata of fast-spiking neurons may be essential for fast and precise sensory transmission and synaptic inhibition in the brain.
| S-EPMC4987413 | biostudies-literature
Project description:Neural circuits and behavior are shaped during developmental phases of maximal plasticity known as sensitive or critical periods. Neural correlates of sensory critical periods have been identified, but their roles remain unclear. Factors that define critical periods in sensorimotor circuits and behavior are not known. Birdsong learning in the zebra finch occurs during a sensitive period similar to that for human speech. We now show that perineuronal nets, which correlate with sensory critical periods, surround parvalbumin-positive neurons in brain areas that are dedicated to singing. The percentage of both total and parvalbumin-positive neurons with perineuronal nets increased with development. In HVC (this acronym is the proper name), a song area important for sensorimotor integration, the percentage of parvalbumin neurons with perineuronal nets correlated with song maturity. Shifting the vocal critical period with tutor song deprivation decreased the percentage of neurons that were parvalbumin positive and the relative staining intensity of both parvalbumin and a component of perineuronal nets. Developmental song learning shares key characteristics with sensory critical periods, suggesting shared underlying mechanisms.
| S-EPMC2769505 | biostudies-literature
Project description:ObjectivePerineuronal nets (PN) form a specialized extracellular matrix around certain highly active neurons within the central nervous system and may help to stabilize synaptic contacts, promote local ion homeostasis, or play a protective role. Within the ocular motor system, excitatory burst neurons and omnipause neurons are highly active cells that generate rapid eye movements - saccades; both groups of neurons contain the calcium-binding protein parvalbumin and are ensheathed by PN. Experimental lesions of excitatory burst neurons and omnipause neurons cause slowing or complete loss of saccades. Selective palsy of saccades in humans is reported following cardiac surgery, but such cases have shown normal brainstem neuroimaging, with only one clinicopathological study that demonstrated paramedian pontine infarction. Our objective was to test the hypothesis that lesions of PN surrounding these brainstem saccade-related neurons may cause saccadic palsy.MethodsTogether with four controls we studied the brain of a patient who had developed a permanent selective saccadic palsy following cardiac surgery and died several years later. Sections of formalin-fixed paraffin-embedded brainstem blocks were applied to double-immunoperoxidase staining of parvalbumin and three different components of PN. Triple immunofluorescence labeling for all PN components served as internal controls. Combined immunostaining of parvalbumin and synaptophysin revealed the presence of synapses.ResultsExcitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.InterpretationOur findings support current models and experimental studies of the brainstem saccade-generating neurons and indicate that damage to PN may permanently impair the function of these neurons that the PN ensheathe. How a postulated hypoxic mechanism could selectively damage the PN remains unclear. We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.
| S-EPMC4489868 | biostudies-literature
Project description:Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN), but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the mouse DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity. When memories are fully acquired, PNNs are restored. Enzymatic digestion of PNNs in the DCN improves EBC learning, but intact PNNs are necessary for memory retention. At the structural level, PNN removal induces significant synaptic rearrangements in vivo, resulting in increased inhibition of DCN baseline activity in awake behaving mice. Together, these results demonstrate that PNNs are critical players in the regulation of cerebellar circuitry and function.
| S-EPMC7104182 | biostudies-literature
Project description:Songbirds learn their vocalizations during developmental sensitive periods of song memorization and sensorimotor learning. Some seasonal songbirds, called open-ended learners, recapitulate transitions from sensorimotor learning and song crystallization on a seasonal basis during adulthood. In adult male canaries, sensorimotor learning occurs each year in autumn and leads to modifications of the syllable repertoire during successive breeding seasons. We previously showed that perineuronal nets (PNN) expression in song control nuclei decreases during this sensorimotor learning period. Here we explored the causal link between PNN expression in adult canaries and song modification by enzymatically degrading PNN in HVC, a key song control system nucleus. Three independent experiments identified limited effects of the PNN degradation in HVC on the song structure of male canaries. They clearly establish that presence of PNN in HVC is not required to maintain general features of crystallized song. Some suggestion was collected that PNN are implicated in the stability of song repertoires but this evidence is too preliminary to draw firm conclusions and additional investigations should consider producing PNN degradations at specified time points of the seasonal cycle. It also remains possible that once song has been crystallized at the beginning of the first breeding season, PNN no longer play a key role in determining song structure; this could be tested by treatments with chondroitinase ABC at key steps in ontogeny. It would in this context be important to develop multiple stereotaxic procedures allowing the simultaneous bilateral degradation of PNN in several song control nuclei for extended periods.
| S-EPMC8396724 | biostudies-literature
Project description:One of the most pernicious characteristics of alcohol use disorder is the compulsion to drink despite negative consequences. The insular cortex controls decision making under conditions of risk or conflict. Cortical activity is tightly controlled by inhibitory interneurons that are often enclosed by specialized extracellular matrix structures known as perineuronal nets (PNNs), which regulate neuronal excitability and plasticity. The density of PNNs in the insula increases after repeated bouts of binge drinking, suggesting that they may play a role in the transition from social to compulsive, or aversion-resistant, drinking. Here, we investigated whether insular PNNs play a role in aversion-resistant alcohol drinking using a mouse model in which ethanol was adulterated with the bitter tastant quinine. Disrupting PNNs in the insula rendered mice more sensitive to quinine-adulterated ethanol but not ethanol alone. Activation of the insula, as measured by c-fos expression, occurred during aversion-resistant drinking and was further enhanced by elimination of PNNs. These results demonstrate that PNNs control the activation of the insula during aversion-resistant drinking and suggest that proper excitatory/inhibitory balance is important for decision making under conditions of conflict. Disrupting PNNs in the insula or optimizing insula activation may be a novel strategy to reduce aversion-resistant drinking.
| S-EPMC7032993 | biostudies-literature
Project description:Perineuronal nets (PNNs) are widely present in the hypothalamus, and are thought to provide physical protection and ion buffering for neurons and regulate their synaptic plasticity and intracellular signaling. Recent evidence indicates that PNNs in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated are not fully understood. In the present study, we examined whether PNNs in various hypothalamic regions in mice can be regulated by sex, gonadal hormones, dietary interventions, or their interactions. We demonstrated that gonadal hormones are required to maintain normal PNNs in the arcuate nucleus of hypothalamus in both male and female mice. In addition, PNNs in the terete hypothalamic nucleus display a sexual dimorphism with females higher than males, and high-fat diet feeding increases terete PNNs only in female mice but not in male mice. On the other hand, PNNs in other hypothalamic regions are not influenced by sex, gonadal hormones or dietary interventions. In summary, we demonstrated that hypothalamic PNNs are regulated in a region-specific manner and these results provide a framework to further investigate the potential functions of PNNs in regulating energy/glucose homeostasis at the interplay of sex, gonadal hormones and diets.
| S-EPMC8355523 | biostudies-literature