Subiculum network excitability is increased in a rodent model of temporal lobe epilepsy.
In this study, we used in vitro electrophysiology along with immunohistochemistry and molecular techniques to study the subiculum--a limbic structure that gates the information flow from and to the hippocampus--in pilocarpine-treated epileptic rats. Comparative data were obtained from age-matched nonepileptic controls (NEC). Subicular neurons in hippocampal-entorhinal cortex (EC) slices of epileptic rats were: (i) hyperexcitable when activated by CA1 or EC inputs; and (ii) generated spontaneous postsynaptic potentials at higher frequencies than NEC cells. Analysis of pharmacologically isolated, GABA(A) receptor-mediated inhibitory postsynaptic potentials revealed more positive reversal potentials in epileptic tissue (-67.8 +/- 6.3 mV, n = 16 vs. -74.8 +/- 3.6 mV in NEC, n = 13; P < 0.001) combined with a reduction in peak conductance (17.6 +/- 11.3 nS vs. 41.1 +/- 26.7 nS in NEC; P < 0.003). These electrophysiological data correlated in the epileptic subiculum with (i) reduced levels of mRNA expression and immunoreactivity of the neuron-specific potassium-chloride cotransporter 2; (ii) decreased number of parvalbumin-positive cells; and (iii) increased synaptophysin (a putative marker of sprouting) immunoreactivity. These findings identify an increase in network excitability within the subiculum of pilocarpine-treated, epileptic rats and point at a reduction in inhibition as an underlying mechanism.
de Guzman
Philip
P
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Inaba
Yuji
Y
Biagini
Giuseppe
G
Baldelli
Enrica
E
Mollinari
Cristiana
C
Merlo
Daniela
D
Avoli
Massimo
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D010320:Parvalbumins / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000096922:K Cl- Cotransporters
D015415:Biomarkers; D003292:Convulsants; D010320:Parvalbumins; D010862:Pilocarpine; D027981:Symporters; D016708:Synaptophysin; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters