Changes of AMPA receptor properties in the neocortex and hippocampus following pilocarpine-induced status epilepticus in rats.
Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. The lithium-pilocarpine model in rodents reproduces some of the main features of human TLE. Three-week-old Wistar rats were used in this study. The changes in AMPA receptor subunit composition were investigated in several brain areas, including the medial prefrontal cortex (mPFC), the temporal cortex (TC), and the dorsal (DH) and ventral hippocampus (VH) during the first week following pilocarpine-induced status epilepticus (PILO-induced SE). In the hippocampus, GluA1 and GluA2 mRNA expression slightly decreased after PILO-induced SE and returned to the initial level on the seventh day. We did not detect any significant changes in mRNA expression of the GluA1 and GluA2 subunits in the TC, whereas in the mPFC we observed a significant increase of GluA1 mRNA expression on the third day and a decrease in GluA2 mRNA expression during the entire first week. Accordingly, the GluA1/GluA2 expression ratio increased in the mPFC, and the functional properties of the pyramidal cell excitatory synapses were disturbed. Using whole-cell voltage-clamp recordings, we found that on the third day following PILO-induced SE, isolated mPFC pyramidal neurons showed an inwardly rectifying current-voltage relation of kainate-evoked currents, suggesting the presence of GluA2-lacking calcium-permeable AMPARs (CP-AMPARs). IEM-1460, a selective antagonist of CP-AMPARs, significantly reduced the amplitude of evoked EPSC in pyramidal neurons from mPFC slices on the first and third days, but not on the seventh day. The antagonist had no effects on EPSC amplitude in slices from control animals. Thus, our data demonstrate that PILO-induced SE affects subunit composition of AMPARs in different brain areas, including the mPFC. SE induces transient (up to few days) incorporation of CP-AMPARs in the excitatory synapses of mPFC pyramidal neurons, which may disrupt normal circuitry functions.
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (IEPhB), 44, Toreza prospekt, Saint Petersburg 194223, Russia.
Sergey L
SL
Malkin
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (IEPhB), 44, Toreza prospekt, Saint Petersburg 194223, Russia.
Dmitry V
DV
Amakhin
Institute of Experimental Medicine (FSBSI "IEM"), 12, Akademik Pavlov Street, Saint Petersburg 197376, Russia.
Ekaterina A
EA
Veniaminova
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (IEPhB), 44, Toreza prospekt, Saint Petersburg 194223, Russia.
Kira Kh
KKh
Kim
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (IEPhB), 44, Toreza prospekt, Saint Petersburg 194223, Russia; Institute of Experimental Medicine (FSBSI "IEM"), 12, Akademik Pavlov Street, Saint Petersburg 197376, Russia.
Olga E
OE
Zubareva
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (IEPhB), 44, Toreza prospekt, Saint Petersburg 194223, Russia; St. Petersburg State University, 7-9, Universitetskaya nab., Saint Petersburg 199034, Russia.
Lev G
LG
Magazanik
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (IEPhB), 44, Toreza prospekt, Saint Petersburg 194223, Russia. Electronic address: aleksey_zaitsev@mail.ru.
Aleksey V
AV
Zaitsev
D000818:Animals; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D018091:Receptors, AMPA; D010862:Pilocarpine
GluA2-lacking AMPA receptors; excitatory synapse; medial prefrontal cortex; mesial temporal lobe epilepsy; pyramidal neuron