Expression of GABAA receptor subunits in the hippocampus of the rat after kainic acid-induced seizures

Sperk, Günther; Schwarzer, Christoph; Tsunashima, Koichi; Kandlhofer, Susanne

doi:10.1016/s0920-1211(98)00046-1

Cited by 76 publications

(52 citation statements)

References 32 publications

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“…Such changes are generally interpreted as indicating a decrease in presynaptic release probability (Lisman et al 2007; but see Manita et al 2007;Markram et al 1998;Zucker and Regehr 2002). Postsynaptic alterations, such as changes in GABA A receptor subunit composition with expression of receptors containing the ␣4 subunit, do occur in both chronic epilepsy models (Schwarzer et al 1997;Sperk et al 1998) and human epilepsy (Brooks-Kayal et al 1999) and could affect the kinetics and PPR of eIPSCs (Lagrange et al 2007). However, such changes are associated with increased depression in responses to pairs or trains of stimuli, results contrary to those in the present experiments (e.g., Fig.…”

Section: Ppr For Monosynaptic Ipscs Is Increased In Layer V Pyramidalcontrasting

confidence: 77%

Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy

Faria

Prince

2010

Journal of Neurophysiology

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Faria LC, Prince DA. Presynaptic inhibitory terminals are functionally abnormal in a rat model of posttraumatic epilepsy. J Neurophysiol 104: 280-290, 2010. First published May 19, 2010 doi:10.1152/jn.00351.2010. Partially isolated "undercut" neocortex with intact pial circulation is a well-established model of posttraumatic epileptogenesis. Results of previous experiments showed a decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs) in layer V pyramidal (Pyr) neurons of undercuts. We further examined possible functional abnormalities in GABAergic inhibition in rat epileptogenic neocortical slices in vitro by recording whole cell monosynaptic IPSCs in layer V Pyr cells and fast-spiking (FS) GABAergic interneurons using a paired pulse paradigm. Compared with controls, IPSCs in Pyr neurons of injured slices showed increased threshold and decreased peak amplitude at threshold, decreased input/output slopes, increased failure rates, and a shift from paired pulse depression toward paired pulse facilitation (increased paired pulse ratio or PPR). Increasing [Ca 2ϩ ] o from 2 to 4 mM partially reversed these abnormalities in Pyr cells of the epileptogenic tissue. IPSCs onto FS cells also had an increased PPR and failures. Blockade of GABA B receptors did not affect the paired results. These findings suggest that there are functional alterations in GABAergic presynaptic terminals onto both Pyr and FS cells in this model of posttraumatic epileptogenesis. I N T R O D U C T I O NPartially isolated "undercut" (UC) or "injured" neocortex is a well established in vivo model of posttraumatic epileptogenesis in cats and monkeys (Echlin and Battista 1963;Echlin and McDonald 1954;Grafstein and Sastry 1957;Sharpless 1969; reviewed in Halpern 1972). Spontaneous (s) and evoked (e) epileptiform activity persists in rodent neocortical slices cut through the UC neocortex and maintained in vitro (Hoffman et al. 1994;Prince and Tseng 1993;Salin et al. 1995; reviewed in Graber and Prince 2006). Alterations in glutamatergic excitatory synaptic activity/connectivity are present in this model and likely contribute to the development of hyperexcitability (Jin et al. 2006;Li and Prince 2002;Li et al. 2005;Salin et al. 1995).Results of anatomical and electrophysiological experiments in UC cortex indicate that decreases in GABAergic inhibitory activity/connectivity may also contribute to epileptogenesis. Biocytin-filled axons of fast-spiking (FS) GABAergic interneurons in the chronically epileptogenic cortex are structurally abnormal with decreased bouton size and marked reduction in axonal lengths ). Such alterations in presynaptic inhibitory terminals might be associated with functional abnormalities such as increased failure rate, decreased amplitude of inhibitory postsynaptic currents (IPSCs), and decreased probability of GABA release (Pr) that would make inhibitory transmission less effective (Harris and Sultan 1995;Pierce and Lewin 1994). There is also a decrease in the frequency of miniature inhibitory post synapt...

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Section: Ppr For Monosynaptic Ipscs Is Increased In Layer V Pyramidalcontrasting

confidence: 77%

Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy

Faria

Prince

2010

Journal of Neurophysiology

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“…For example, GAD65 and GAD67 show increased expression during excitotoxic seizures (10), presumably increasing the GABA production in an activity-dependent manner, and the GABA transporters GAT1 and GAT3 show reduced expression during excitotoxic seizures and ischemic insults (27,44), presumably leading to reduced GABA uptake and increased extracellular GABA levels. Also, substantial alterations in the subunit expression of GABA A Rs and GABA B Rs have been reported in response to excitotoxic and ischemic events (14,38,42), and decreased KCC2 expression has been found during kindling-induced seizures, where it may contribute to neuronal death (39). Still, in mammalian tissues, the physiological/pathophysiological responses to ischemia and excitotoxicity are not easy to interpret.…”

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confidence: 99%

Expression of genes involved in GABAergic neurotransmission in anoxic crucian carp brain (Carassius carassius)

Ellefsen

Stensløkken

Fagernes

et al. 2009

Physiological Genomics

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Ellefsen S, Stensløkken K, Fagernes CE, Kristensen TA, Nilsson GE. Expression of genes involved in GABAergic neurotransmission in anoxic crucian carp brain (Carassius carassius). Physiol Genomics 36: 61-68, 2009. First published October 28, 2008 doi:10.1152/physiolgenomics.90301.2008.-The crucian carp, Carassius carassius, survives days to months without oxygen, depending on temperature. In the anoxic crucian carp brain, increased GABAergic inhibition, mediated by increased extracellular levels of GABA, has been shown to suppress electric activity and ATP consumption. To investigate an involvement of gene expression in this response, we utilized real-time RT-PCR to test the effect of 1 and 7 days anoxia (8°C) on the expression of 22 genes, including nine GABAA receptor subunits (␣1-6, ␤2, ␦, and ␥2), three GABAB receptor subunits (GB1a-1b and GB2), three enzymes involved in GABA metabolism (GAD65 and GAD67, GABAT), four GABA transporters (GAT1, 2a-b and 3), two GABAA receptor-associated proteins (GABARAP 1 and 2), and the K ϩ /Cl Ϫ cotransporter KCC2. While the expression of GABAA receptor subunits was dominated by ␣4-, ␣6-, and ␦-subunits, all of which are located to extrasynaptic sites in mammalian brains and respond to elevations in extracellular levels of GABA by showing tonic activity patterns, the expression of GABA transporters was dominated by GAT2 (a and b) and GAT3, which also show extrasynaptic location in mammals. These expression patterns differ from those observed in mammals and may be a prerequisite for GABAergic inhibition of anoxic metabolic rate in crucian carp. Furthermore, while the expression of the majority of the genes was largely unaltered by anoxia, the expression of GAT2 and GAT3 decreased to 20%. This suggests impairment of GABA transport, which could be a mechanism behind the accumulation of extracellular GABA and the increased GABAergic inhibition.GABA; GABA receptor; GABA transporter; external RNA control SINCE GABA IS THE DOMINANT inhibitory neurotransmitter in vertebrate brains, GABAergic neurotransmission has been suggested to function as an endogenous defense against excitotoxic events, such as the excessive release of glutamate during periods of ischemia/anoxia (26). However, GABAergic activity seems to be lowered rather than enhanced in ischemic mammalian brains, resulting in neuronal hyperexcitability and cell death (41). Thus, efforts have been made to reverse this process, and several studies have found that artificially increased GABAergic activity results in increased neuroprotection (41).Interestingly, anoxia induces increased GABA levels and GABAergic activity in brains of vertebrate species that tolerate prolonged periods of oxygen depletion, such as fish of the genus Carassius and freshwater turtles of genera Chrysemys and Trachemys. For example, while crucian carp (Carassius carassius) brains show a doubling of extracellular GABA levels after 6 h of anoxia and a fivefold increase in tissue GABA levels after prolonged anoxia (32, 19), freshwater turtle brains show a ...

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“…Intraperitoneal KA in rat Hippocampus ↑ in DG interneurons [ 85 ] ↓ in CA1 at 1 month Intrahippocampal KA in mice Hippocampus ↑ in DG [ 6 ] ↓ in CA1 sr and slm and CA3 at 1 month…”

Section: Gaba-aα5mentioning

confidence: 99%

“…Intraperitoneal KA in rat Hippocampus ↑ in CA1-CA3 in pyramidal-shaped perikaryon at 1 month [ 85 ] Intrahippocampal KA mice Hippocampus ↓ in CA1 sr and slm and CA3 at 1 month [ 6 ] Pilocarpine in rat Hippocampus ↑ in DG [ 20 ] ↓ in CA3, hilus…”

Section: Gaba-aα3mentioning

confidence: 99%

Are Alterations in Transmitter Receptor and Ion Channel Expression Responsible for Epilepsies?

Powell

Łukasiuk

O’Brien

et al. 2014

Issues in Clinical Epileptology: A View From the Bench

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Neuronal voltage-gated ion channels and ligand-gated synaptic receptors play a critical role in maintaining the delicate balance between neuronal excitation and inhibition within neuronal networks in the brain. Changes in expression of voltage-gated ion channels, in particular sodium, hyperpolarization-activated cyclic nucleotide-gated (HCN) and calcium channels, and ligand-gated synaptic receptors, in particular GABA and glutamate receptors, have been reported in many types of both genetic and acquired epilepsies, in animal models and in humans. In this chapter we review these and discuss the potential pathogenic role they may play in the epilepsies.

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Expression of GABAA receptor subunits in the hippocampus of the rat after kainic acid-induced seizures

Cited by 76 publications

References 32 publications

Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy

Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy

Expression of genes involved in GABAergic neurotransmission in anoxic crucian carp brain (Carassius carassius)

Are Alterations in Transmitter Receptor and Ion Channel Expression Responsible for Epilepsies?

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