MMPs and soluble ICAM-5 increase neuronal excitability within in vitro networks of hippocampal neurons

Mark Niedringhaus, Xin Chen, Rhonda Dzakpasu, Katherine Conant

Research output: Contribution to journalArticle

Abstract

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are released from neurons in an activity dependent manner. Published studies suggest their activity is important to varied forms of learning and memory. At least one MMP can stimulate an increase in the size of dendritic spines, structures which represent the post synaptic component for a large number of glutamatergic synapses. This change may be associated with increased synaptic glutamate receptor incorporation, and an increased amplitude and/or frequency of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) mini excitatory post-synaptic currents (EPSCs). An associated increase in the probability of action potential occurrence would be expected. While the mechanism(s) by which MMPs may influence synaptic structure and function are not completely understood, MMP dependent shedding of specific cell adhesion molecules (CAMs) could play an important role. CAMs are ideally positioned to be cleaved by synaptically released MMPs, and shed N terminal domains could potentially interact with previously unengaged integrins to stimulate dendritic actin polymerization with spine expansion. In the present study, we have used multielectrode arrays (MEAs) to investigate MMP and soluble CAM dependent changes in neuronal activity recorded from hippocampal cultures. We have focused on intercellular adhesion molecule-5 (ICAM-5) in particular, as this CAM is expressed on glutamatergic dendrites and shed in an MMP dependent manner. We show that chemical long-term potentiation (cLTP) evoked changes in recorded activity, and the dynamics of action potential bursts in particular, are altered by MMP inhibition. A blocking antibody to β1 integrins has a similar effect. We also show that the ectodomain of ICAM-5 can stimulate β1 integrin dependent increases in spike counts and burst number. These results support a growing body of literature suggesting that MMPs have important effects on neuronal excitability. They also support the possibility that MMP dependent shedding of specific synaptic CAMs can contribute to these effects.

Original languageEnglish (US)
Article numbere42631
JournalPLoS One
Volume7
Issue number8
DOIs
StatePublished - Aug 13 2012
Externally publishedYes

Fingerprint

Cell Adhesion Molecules
metalloproteinases
Matrix Metalloproteinases
Neurons
adhesion
neurons
cell adhesion
integrins
Integrins
sheds
action potentials
Action Potentials
In Vitro Techniques
Isoxazoles
Endopeptidases
Dendritic Spines
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neurotransmitter Receptor
Blocking Antibodies
Long-Term Potentiation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

MMPs and soluble ICAM-5 increase neuronal excitability within in vitro networks of hippocampal neurons. / Niedringhaus, Mark; Chen, Xin; Dzakpasu, Rhonda; Conant, Katherine.

In: PLoS One, Vol. 7, No. 8, e42631, 13.08.2012.

Research output: Contribution to journalArticle

Niedringhaus, Mark ; Chen, Xin ; Dzakpasu, Rhonda ; Conant, Katherine. / MMPs and soluble ICAM-5 increase neuronal excitability within in vitro networks of hippocampal neurons. In: PLoS One. 2012 ; Vol. 7, No. 8.
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