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In vitro CNS tissue analogues formed by self-organisation of reaggregated post-natal brain tissue

In vitro CNS tissue analogues formed by self-organisation of reaggregated post-natal brain tissue
In vitro CNS tissue analogues formed by self-organisation of reaggregated post-natal brain tissue
In this paper we report the characterization of ‘Hi-Spot’ cultures formed by the re-aggregation of dissociated post-natal CNS tissue grown at an air-liquid interface. This produces a self-organised, dense, organotypic cellular network. Western blot, immunohistochemical, viral transfection and electron microscopy analyses reveal neuronal and glial populations, and the development of a synaptic network. Multi-electrode array recordings show synaptically driven network activity that develops through time from single unit spiking activity to global network bursting events. This activity is blocked by tetanus toxin and modified by antagonists of glutamatergic and GABAergic receptors suggesting tonic activity of excitatory and inhibitory synaptic signaling. The tissue-like properties of these cultures has been further demonstrated by their relative insensitivity to glutamate toxicity. Exposure to millimolar concentrations of glutamate for hours is necessary to produce significant excitotoxic neuronal death, as in vivo. We conclude that “Hi-Spots” are biological analogues of CNS tissue at a level of complexity that allows for detailed functional analyses of emergent neuronal network properties.
electrophysiology, excitotoxicity, multi-electrode array, organotypic, synapse, tissue engineering
0022-3042
1020-1032
Bailey, Joanne L.
08594c8d-6c25-47c6-ba7d-44365f53f573
O’Connor, Vincent
3c336b62-f3ef-4f78-a44c-ddc7b47bac3f
Hannah, Matthew
afcdc15a-c066-4f15-a165-22af39ab8810
Hewlett, Lindsay
6fa80607-d5f4-4bd6-af36-bbefe9af3bdb
Biggs, Thelma E.
8f59e2e1-6d75-4337-8a37-1dd73852babb
Sundstrom, Lars E.
bb62018d-0157-4274-a865-448ed12934bd
Findlay, Matt W.
3dacdad1-2796-4bbf-81e3-9f916c6a55be
Chad, John E.
d220e55e-3c13-4d1d-ae9a-1cfae8ccfbe1
Bailey, Joanne L.
08594c8d-6c25-47c6-ba7d-44365f53f573
O’Connor, Vincent
3c336b62-f3ef-4f78-a44c-ddc7b47bac3f
Hannah, Matthew
afcdc15a-c066-4f15-a165-22af39ab8810
Hewlett, Lindsay
6fa80607-d5f4-4bd6-af36-bbefe9af3bdb
Biggs, Thelma E.
8f59e2e1-6d75-4337-8a37-1dd73852babb
Sundstrom, Lars E.
bb62018d-0157-4274-a865-448ed12934bd
Findlay, Matt W.
3dacdad1-2796-4bbf-81e3-9f916c6a55be
Chad, John E.
d220e55e-3c13-4d1d-ae9a-1cfae8ccfbe1

Bailey, Joanne L., O’Connor, Vincent, Hannah, Matthew, Hewlett, Lindsay, Biggs, Thelma E., Sundstrom, Lars E., Findlay, Matt W. and Chad, John E. (2011) In vitro CNS tissue analogues formed by self-organisation of reaggregated post-natal brain tissue. Journal of Neurochemistry, 117 (6), 1020-1032. (doi:10.1111/j.1471-4159.2011.07276.x). (PMID:21592119)

Record type: Article

Abstract

In this paper we report the characterization of ‘Hi-Spot’ cultures formed by the re-aggregation of dissociated post-natal CNS tissue grown at an air-liquid interface. This produces a self-organised, dense, organotypic cellular network. Western blot, immunohistochemical, viral transfection and electron microscopy analyses reveal neuronal and glial populations, and the development of a synaptic network. Multi-electrode array recordings show synaptically driven network activity that develops through time from single unit spiking activity to global network bursting events. This activity is blocked by tetanus toxin and modified by antagonists of glutamatergic and GABAergic receptors suggesting tonic activity of excitatory and inhibitory synaptic signaling. The tissue-like properties of these cultures has been further demonstrated by their relative insensitivity to glutamate toxicity. Exposure to millimolar concentrations of glutamate for hours is necessary to produce significant excitotoxic neuronal death, as in vivo. We conclude that “Hi-Spots” are biological analogues of CNS tissue at a level of complexity that allows for detailed functional analyses of emergent neuronal network properties.

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More information

Accepted/In Press date: 12 April 2011
e-pub ahead of print date: 19 May 2011
Published date: June 2011
Keywords: electrophysiology, excitotoxicity, multi-electrode array, organotypic, synapse, tissue engineering
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 185407
URI: https://eprints.soton.ac.uk/id/eprint/185407
ISSN: 0022-3042
PURE UUID: 954b64f8-ffab-4694-aaec-0a6531c52afb
ORCID for John E. Chad: ORCID iD orcid.org/0000-0001-6442-4281

Catalogue record

Date deposited: 10 May 2011 13:48
Last modified: 06 Jun 2018 13:17

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