TY - JOUR
T1 - Altered pharmacology and GABA-A receptor subunit expression in dorsal midline thalamic neurons in limbic epilepsy
AU - Rajasekaran, Karthik
AU - Sun, Chengsan
AU - Bertram, Edward H.
N1 - Funding Information:
We thank John M. Williamson for excellent technical assistance, David Sloan for silver staining data, and Dr. Jaideep Kapur for his thoughtful comments. This work was supported by the National Institutes of Health grant NS-25605 (EHB), NS-40337 (JK), NS-44370 (JK) and NS-058204 (JK).
PY - 2009/1
Y1 - 2009/1
N2 - The mediodorsal (MD) and paraventricular (PV) thalamic nuclei play a significant role in limbic epilepsy, and previous reports have shown changes in GABA-A receptor (GABAAR) mediated synaptic function. In this study, we examined changes in the pharmacology of GABAergic drugs and the expression of the GABAAR subunits in the MD and PV neurons in epilepsy. We observed nucleus specific changes in the sensitivity of sIPSCs to zolpidem and phenobarbital in MD and PV neurons from epileptic animals. In contrast, the magnitude of change in electrically evoked response (eIPSC) to zolpidem and phenobarbital were uniformly diminished in both MD and PV neurons in epilepsy. Immunohistochemical studies revealed that in epilepsy, there was a reduction in GAD65 expression and NeuN positive neurons in the MD neurons. Also, there was a decrease in immunoreactivity of the α1 and β2/3 subunit of GABAARs, but not the γ2 of the GABAAR in both MD and PV in epilepsy. These findings demonstrate significant alterations in the pharmacology of GABA and GABAARs in a key region for seizure generation, which may have implications for the physiology and pharmacology of limbic epilepsy.
AB - The mediodorsal (MD) and paraventricular (PV) thalamic nuclei play a significant role in limbic epilepsy, and previous reports have shown changes in GABA-A receptor (GABAAR) mediated synaptic function. In this study, we examined changes in the pharmacology of GABAergic drugs and the expression of the GABAAR subunits in the MD and PV neurons in epilepsy. We observed nucleus specific changes in the sensitivity of sIPSCs to zolpidem and phenobarbital in MD and PV neurons from epileptic animals. In contrast, the magnitude of change in electrically evoked response (eIPSC) to zolpidem and phenobarbital were uniformly diminished in both MD and PV neurons in epilepsy. Immunohistochemical studies revealed that in epilepsy, there was a reduction in GAD65 expression and NeuN positive neurons in the MD neurons. Also, there was a decrease in immunoreactivity of the α1 and β2/3 subunit of GABAARs, but not the γ2 of the GABAAR in both MD and PV in epilepsy. These findings demonstrate significant alterations in the pharmacology of GABA and GABAARs in a key region for seizure generation, which may have implications for the physiology and pharmacology of limbic epilepsy.
KW - GABA-A receptor
KW - Mediodorsal thalamus
KW - Paraventricular thalamus
KW - Phenobarbital
KW - Temporal lobe epilepsy
KW - Zolpidem
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U2 - 10.1016/j.nbd.2008.09.023
DO - 10.1016/j.nbd.2008.09.023
M3 - Article
C2 - 18992345
AN - SCOPUS:57449109489
SN - 0969-9961
VL - 33
SP - 119
EP - 132
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -