N-Acetylgalactosamine Positive Perineuronal Nets in the Saccade-Related-Part of the Cerebellar Fastigial Nucleus Do Not Maintain Saccade Gain

Mueller, Adrienne; Davis, Adam; Carlson, Steven S.; Robinson, Farrel R.

doi:10.1371/journal.pone.0086154

Cited by 4 publications

(6 citation statements)

References 49 publications

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“…Two pieces of evidence suggest that PNNs in the cerebellar nuclei serve a purpose other than inhibiting synaptic plasticity. (1) We recently showed that dissolving PNNs in the cerebellar nuclei had no impact on the strength or persistence of changes in saccade size elicited by long term saccade adaptation [ 72 ]. (2) As we show in Figure 10 , one of the ligands most likely to mediate inhibition of synaptic plasticity, PTP σ , is not expressed in the cerebellar nuclei in a manner consistent with this function.…”

Section: Discussionmentioning

confidence: 99%

Distribution of N-Acetylgalactosamine-Positive Perineuronal Nets in the Macaque Brain: Anatomy and Implications

et al. 2016

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Perineuronal nets (PNNs) are extracellular molecules that form around neurons near the end of critical periods during development. They surround neuronal cell bodies and proximal dendrites. PNNs inhibit the formation of new connections and may concentrate around rapidly firing inhibitory interneurons. Previous work characterized the important role of perineuronal nets in plasticity in the visual system, amygdala, and spinal cord of rats. In this study, we use immunohistochemistry to survey the distribution of perineuronal nets in representative areas of the primate brain. We also document changes in PNN prevalence in these areas in animals of different ages. We found that PNNs are most prevalent in the cerebellar nuclei, surrounding >90% of the neurons there. They are much less prevalent in cerebral cortex, surrounding less than 10% of neurons in every area that we examined. The incidence of perineuronal nets around parvalbumin-positive neurons (putative fast-spiking interneurons) varies considerably between different areas in the brain. Our survey indicates that the presence of PNNs may not have a simple relationship with neural plasticity and may serve multiple functions in the central nervous system.

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Section: Discussionmentioning

confidence: 99%

Distribution of N-Acetylgalactosamine-Positive Perineuronal Nets in the Macaque Brain: Anatomy and Implications

et al. 2016

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“…Saccades are an ideal system for studying neural control of movement since they are well understood and can be measured precisely [ 33 , 57 ]. The feasibility of experimentally digesting chondroitin sulfate chains of PN with the enzyme chondroitinase ABC [ 58 ] has been shown in macaque fastigial nucleus [ 59 ]. Similar methods could be applied in the PPRF and RIMLF.…”

Section: Discussionmentioning

confidence: 99%

Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal Nets

et al. 2015

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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.

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“…Second, it should be possible to selectively lesion PN in macaques and measure the effects on specific types of eye movements; the brainstem control of saccades would seem a good place to start, given the well‐established neural substrate for these eye movements. Such an approach has already been shown to be feasible through injecting the enzyme chondroitinase ABC to digest chondroitin sulfate chains of PN in the monkey fastigial nucleus neurons and performing saccade‐adaptation experiments . If an attempt to lesion PN surrounding PBN and OPN caused a saccadic palsy, then this might serve as a reductionist model to study the effects of lesioning PN in other areas of the brain and an accessible means to investigate the potential and mechanisms of action of putative therapies .…”

Section: Discussionmentioning

confidence: 99%

Saccadic palsy following cardiac surgery: a review and new hypothesis

Eggers

Horn

Roeber

et al. 2015

Annals of the New York Academy of Sciences

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The ocular motor system provides several advantages for studying the brain, including well-defined populations of neurons that contribute to specific eye movements. Generation of rapid eye movements (saccades) depends on excitatory burst neurons (EBNs) and omnipause neurons (OPNs) within the brain stem; both types of cell are highly active. Experimental lesions of EBNs and OPNs cause slowing or complete loss of saccades. We report a patient who developed a permanent, selective saccadic palsy following cardiac surgery. When she died several years later, surprisingly, autopsy showed preservation of EBNs and OPNs. We therefore considered other mechanisms that could explain her saccadic palsy. Recent work has shown that both EBNs and OPNs are ensheathed by perineuronal nets (PNs), which are specialized extracellular matrix structures that may help stabilize synaptic contacts, promote local ion homeostasis, or play a protective role in certain highly active neurons. Here, we review the possibility that damage to PNs, rather than to the neurons they support, could lead to neuronal dysfunction—such as saccadic palsy. We also suggest how future studies could test this hypothesis, which may provide insights into the vulnerability of other active neurons in the nervous system that depend on PNs.

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N-Acetylgalactosamine Positive Perineuronal Nets in the Saccade-Related-Part of the Cerebellar Fastigial Nucleus Do Not Maintain Saccade Gain

Cited by 4 publications

References 49 publications

Distribution of N-Acetylgalactosamine-Positive Perineuronal Nets in the Macaque Brain: Anatomy and Implications

Distribution of N-Acetylgalactosamine-Positive Perineuronal Nets in the Macaque Brain: Anatomy and Implications

Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal Nets

Saccadic palsy following cardiac surgery: a review and new hypothesis

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