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The effects of acute and chronic applications of kainic acid to the rodent hippocampus

The effects of acute and chronic applications of kainic acid to the rodent hippocampus
The effects of acute and chronic applications of kainic acid to the rodent hippocampus

Kainic acid is an excitotoxin in mammalian brain.  Here the mechanisms underlying the physiological versus the pathological effects of kainate (KA) were compared.  The acute effects were studied on rat hippocampal slices, and the chronic effects in mouse organotypic hippocampal slice cultures (over the course of 7 days).

Two approaches were used:  First, in acute hippocampal slices, receptor selective drugs were used to determine the receptor subtypes involved in the response to KA (15-30 minutes) using simultaneous recordings of evoked field potentials from the stratum pyramidale and s. radiatum of CA1.  The role of CA3 in driving the response in CA1 was determined by repeating these experiments following excision of the CA3.  Second in organotypic mouse hippocampal slice cultures the response to longer applications of KA (2 - 24 hours) was determined using evoked field potential recordings from the s. pyramidale to either CA1 or CA3.

Acute applications of KA reduced the EPSP slopes, initially increased and then related the population spike amplitudes (PSA) and decreased the paired-pulse inhibition. The underlying mechanisms for these effects could be either presynaptic, postsynaptic or a combination of both.  For example, KA may decrease EPSP slope via GluR6 containing receptors on CA1 pyramidal cells, or by presynaptic inhibition at Schaffer collateral terminals via GluR5 containing receptors.  Pharmacological evidence supports the latter, as the GluR5 selective agonist ATPA mimicked this effect of KA, and it was not blocked by the GluR6 antagonist NS102.  A further possibility is that KA may activate GABAergic interneurones via GluR5 containing receptors and this could also result in a decreased EPSP slope.  However, concomitant with the decreased EPSP slope KA also increased population spike amplitude (PSA) and decreased paired-pulse inhibition (PPI), arguing against the involvement of GABA.  CA3 was not required for these effects of KA.

University of Southampton
Cook, Alan
7b75a288-b189-4c85-8122-0f389847ac4a
Cook, Alan
7b75a288-b189-4c85-8122-0f389847ac4a

Cook, Alan (2003) The effects of acute and chronic applications of kainic acid to the rodent hippocampus. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Kainic acid is an excitotoxin in mammalian brain.  Here the mechanisms underlying the physiological versus the pathological effects of kainate (KA) were compared.  The acute effects were studied on rat hippocampal slices, and the chronic effects in mouse organotypic hippocampal slice cultures (over the course of 7 days).

Two approaches were used:  First, in acute hippocampal slices, receptor selective drugs were used to determine the receptor subtypes involved in the response to KA (15-30 minutes) using simultaneous recordings of evoked field potentials from the stratum pyramidale and s. radiatum of CA1.  The role of CA3 in driving the response in CA1 was determined by repeating these experiments following excision of the CA3.  Second in organotypic mouse hippocampal slice cultures the response to longer applications of KA (2 - 24 hours) was determined using evoked field potential recordings from the s. pyramidale to either CA1 or CA3.

Acute applications of KA reduced the EPSP slopes, initially increased and then related the population spike amplitudes (PSA) and decreased the paired-pulse inhibition. The underlying mechanisms for these effects could be either presynaptic, postsynaptic or a combination of both.  For example, KA may decrease EPSP slope via GluR6 containing receptors on CA1 pyramidal cells, or by presynaptic inhibition at Schaffer collateral terminals via GluR5 containing receptors.  Pharmacological evidence supports the latter, as the GluR5 selective agonist ATPA mimicked this effect of KA, and it was not blocked by the GluR6 antagonist NS102.  A further possibility is that KA may activate GABAergic interneurones via GluR5 containing receptors and this could also result in a decreased EPSP slope.  However, concomitant with the decreased EPSP slope KA also increased population spike amplitude (PSA) and decreased paired-pulse inhibition (PPI), arguing against the involvement of GABA.  CA3 was not required for these effects of KA.

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Published date: 2003

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Local EPrints ID: 465061
URI: http://eprints.soton.ac.uk/id/eprint/465061
PURE UUID: 8a5ed0b0-e53d-4e8c-98ab-c78951510d90

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Date deposited: 05 Jul 2022 00:20
Last modified: 05 Jul 2022 04:04

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Author: Alan Cook

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