Modulation of network activity and induction of homeostatic synaptic plasticity by enzymatic removal of heparan sulfates.
Philos Trans R Soc Lond B Biol Sci
; 369(1654): 20140134, 2014 Oct 19.
Article
em En
| MEDLINE
| ID: mdl-25225107
ABSTRACT
Heparan sulfates (HSs) are complex and highly active molecules that are required for synaptogenesis and long-term potentiation. A deficit in HSs leads to autistic phenotype in mice. Here, we investigated the long-term effect of heparinase I, which digests highly sulfated HSs, on the spontaneous bioelectrical activity of neuronal networks in developing primary hippocampal cultures. We found that chronic heparinase treatment led to a significant reduction of the mean firing rate of neurons, particularly during the period of maximal neuronal activity. Furthermore, firing pattern in heparinase-treated cultures often appeared as epileptiform bursts, with long periods of inactivity between them. These changes in network activity were accompanied by an increase in the frequency and amplitude of miniature postsynaptic excitatory currents, which could be described by a linear up-scaling of current amplitudes. Biochemically, we observed an upregulation in the expression of the glutamate receptor subunit GluA1, but not GluA2, and a strong increase in autophosphorylation of α and ß Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), without changes in the levels of kinase expression. These data suggest that a deficit in HSs triggers homeostatic synaptic plasticity and drastically affects functional maturation of neural network.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Heparina Liase
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Heparitina Sulfato
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Hipocampo
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Homeostase
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Plasticidade Neuronal
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Philos Trans R Soc Lond B Biol Sci
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Federação Russa