‘Perineuronal nets’ around cortical interneurons expressing parvalbumin are rich in tenascin

doi:10.1016/0304-3940(93)90579-A

Neuroscience Letters

Volume 162, Issues 1–2, 12 November 1993, Pages 137-140

https://doi.org/10.1016/0304-3940(93)90579-A Get rights and content

Abstract

‘Perineuronal nets’ are ill-known structures enwrapping the cell bodies and proximal dendrites of certain neurons in the brain. It is as yet unclear if they represent a cytological entity or extracellular material. Using immunohistochemical methods we have detected the presence of the extracellular matrix-protein, tenascin, in the ‘perineuronal nets’ surrounding certain cortical interneurons. We have also shown that tenascin antibodies label the circumference of parvalbumin-immunoreactive neurons preferentially. We conclude that this classical matrix protein is a major component of ‘perineuronal nets’. Therefore, ‘perineuronal nets’ may represent sites of privileged adhesion between nerve and glial cells.

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Perineuronal nets (PNNs) are cartilage-like structures of extracellular matrix molecules that enwrap in a net-like manner the cell-body and proximal dendrites of special subsets of neurons. PNNs stabilize their incoming connections and restrict plasticity. Consequently, they have been proposed as a candidate mechanism for drug-induced learning and memory. In the cerebellum, PNNs surround Golgi inhibitory interneurons and both inhibitory and excitatory neurons in the deep cerebellar nuclei (DCN). Previous studies from the lab showed that cocaine-induced conditioned memory increased PNN expression in the granule cell layer of the posterior vermis. The present research aimed to investigate the role of cerebellar PNNs in cocaine-induced conditioned preference. For this purpose, we use the enzyme chondroitinase ABC (ChABC) to digest PNNs at different time points of the learning process to ascertain whether their removal can affect drug-induced memory. Our results show that PNN digestion using ChABC in the posterior vermis (Lobule VIII) did not affect the acquisition of cocaine-induced conditioned preference. However, the removal of PNNs in Lobule VIII -but not in the DCN- disrupted short-term memory of conditioned preference. Moreover, although PNN digestion facilitated the formation of extinction, reinstatement of cocaine-induced conditioned preference was encouraged under PNN digestion. The present findings suggests that PNNs around Golgi interneurons are needed to maintain cocaine-induced Pavlovian memory but also to stabilize extinction memory. Conversely, PNN degradation within the DCN did not affect stability of cocaine-induced memories. Therefore, degradation of PNNs in the vermis might be used as a promising tool to manipulate drug-induced memory.
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Tenascin-C and tenascin-R are expressed in the developing and adult CNS. Only a few reports have described the existence of tenascin-C in PNNs, and tenascin-C-deficient mice show normal PNNs in the adult cerebral cortex, suggesting that tenascin-C is dispensable for PNN formation [85,86]. In contrast, tenascin-R is an integral component of PNNs, and mice lacking tenascin-R show abnormal formation of PNNs that are characterized by diffuse distribution patterns of aggrecan and hyaluronan [87,88].
The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration.
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The number and extent of PNNs that consist of extracellular matrix superstructures surrounding synapses was not altered in hippocampal neurons by exposure to antipsychotic drugs. In contrast treatment of hippocampal neurons with haloperidol led to a slight decrease whereas olanzapine induced a significant increase of the number of structural synapses after 13 days. This differential effect concerning synapse numbers was also reflected in the spontaneous activity of neuronal networks, as monitored on multielectrode arrays (MEAs). In that context, application of haloperidol reduced while olanzapine significantly enhanced network activity. Unexpectedly, flupentixol that is regarded as an FGA caused similar effects than the SGA olanzapine in that it augmented synapse number as well as network activity. Our pilot study provides a proof of concept that the neuron-astrocyte co-culture model can be used to investigate the impact of antipsychotics on pivotal parameters of neuronal cell biology. Thereby, it may support the comparative analysis of antipsychotics applied in the therapy of schizophrenia.
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Citation Excerpt :
The HLT model turn out to be a very far-sighted model not only for the PNN molecular organization but also for the perinodal ECM molecular organization (Bekku et al., 2009). The PNN is a unique ECM structure that is most prominently displayed around GABAergic interneurons, with parvalbumin expressing cells having the highest level of colocalization (Brückner et al., 1993; Celio and Chiquet-Ehrismann, 1993; Morris and Henderson, 2000). The involvement of PNNs in neuronal plasticity has been extensively studied over recent years.
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This chapter will review some of the mechanisms of synaptic plasticity in the developing cerebral cortex, as revealed by neuroanatomical studies. We describe the electron microscopic data that capture synaptogenesis and synapse pruning in detail. The neurotransmitter systems that we will cover are glutamate, gamma-aminobutyric acid (GABA), norepinephrine, and acetylcholine. The topics included in this chapter are not only the important ones but also can best be described as those to which the authors have had the most direct research experience.
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Given that norepinephrine is a permissive factor enabling plasticity of receptive field properties, the shift in the noradrenergic receptor expression from synapses to glia could be a factor contributing to the ending of the CP. Calcium is regarded as an important ion to enable synaptic plasticity. Therefore, synaptic transmission that allows for more Ca²⁺ influx (e.g. via the NR2B-containing N-methyl-d-aspartate receptors (NMDARs)) might be thought to be better than the alternative that allows for less (NR2A-containing NMDARs). However, the rise of NR2A-subunits aligns better with the onset of the CP, and it is the decline of the NR2B-subunits in layer 4 (the thalamocortical (TC) input layer) but not in layers 2/3, that aligns better with the end of the ocular dominance CP. These, among many other observations, point to the importance of considering layer-, and therefore circuit, specific changes during the CP. A structural change that is temporally correlated with developmental plasticity is the postsynaptic protrusions in layer 4 that invaginate the TC axon terminals. These highly specialized structures peak at the CP.
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‘Perineuronal nets’ around cortical interneurons expressing parvalbumin are rich in tenascin

Abstract

J. Neurol. Sci.

Brain Res.

Int. J. Dev. Neurosci.

Cell Calcium

Neuroscience

Seminars Neurosci.

Dev. Biol.

Brain Res.

Adv. Cell Biol.

J. Biol. Chem.

Brain Res.

J. Biol. Chem.

Dev. Biol.

Neuroscience

Neurosci. Res.

Ueber die perizellulären ‘Golgi-Netze’ im Zentralnervensystem

Z. Gesamte Neurol. Psychiatrie

Molecular markers of neuronal subpopulations in layers 4,5,6 of cat primary visual cortex

J. Neurosci.

Chondroitin-sulfate proteoglycan surrounds a subset of human and rat CNS-neurons

J. Neurosci. Res.

Perineuronal nets of glia

J. Hirnforsch.

Restrictin occurs in ‘perineuronal nets’, of the adult rat

Brain Soc. Neurosci. Abstr.

Chick myotendinous antigen. II. A novel extracellular glycoprotein complex consisting of large disulfide-linked subunits

J. Cell. Biol.

Tenascin: an extracellular marker protein involved in tissue interactions during fetal development and oncogenesis

Cell