TY - JOUR
T1 - Rebound burst firing in the reticular thalamus is not essential for pharmacological absence seizures in mice
AU - Lee, Seung Eun
AU - Lee, Jaekwang
AU - Latchoumane, Charles
AU - Lee, Boyoung
AU - Oh, Soo Jin
AU - Saud, Zahangir Alam
AU - Park, Cheongdahm
AU - Sun, Ning
AU - Cheong, Eunji
AU - Chen, Chien Chang
AU - Choi, Eui Ju
AU - Lee, C. Justin
AU - Shin, Hee Sup
PY - 2014/8/12
Y1 - 2014/8/12
N2 - Intrinsic burst and rhythmic burst discharges (RBDs) are elicited by activation of T-type Ca2+ channels in the thalamic reticular nucleus (TRN). TRN bursts are believed to be critical for generation and maintenance of thalamocortical oscillations, leading to the spikeand- wave discharges (SWDs), which are the hallmarks of absence seizures. We observed that the RBDs were completely abolished, whereas tonic firing was significantly increased, in TRN neurons from mice in which the gene for the T-type Ca2+ channel, CaV3.3, was deleted (CaV3.3-/-). Contrary to expectations, there was an increased susceptibility to drug-induced SWDs both in CaV3.3-/- mice and in mice in which the CaV3.3 gene was silenced predominantly in the TRN. CaV3.3-/- mice also showed enhanced inhibitory synaptic drive onto TC neurons. Finally, a double knockout of both CaV3.3 and CaV3.2, which showed complete elimination of burst firing and RBDs in TRN neurons, also displayed enhanced drug-induced SWDs and absence seizures. On the other hand, tonic firing in the TRN was increased in these mice, suggesting that increased tonic firing in the TRN may be sufficient for druginduced SWD generation in the absence of burst firing. These results call into question the role of burst firing in TRN neurons in the genesis of SWDs, calling for a rethinking of the mechanism for absence seizure induction.
AB - Intrinsic burst and rhythmic burst discharges (RBDs) are elicited by activation of T-type Ca2+ channels in the thalamic reticular nucleus (TRN). TRN bursts are believed to be critical for generation and maintenance of thalamocortical oscillations, leading to the spikeand- wave discharges (SWDs), which are the hallmarks of absence seizures. We observed that the RBDs were completely abolished, whereas tonic firing was significantly increased, in TRN neurons from mice in which the gene for the T-type Ca2+ channel, CaV3.3, was deleted (CaV3.3-/-). Contrary to expectations, there was an increased susceptibility to drug-induced SWDs both in CaV3.3-/- mice and in mice in which the CaV3.3 gene was silenced predominantly in the TRN. CaV3.3-/- mice also showed enhanced inhibitory synaptic drive onto TC neurons. Finally, a double knockout of both CaV3.3 and CaV3.2, which showed complete elimination of burst firing and RBDs in TRN neurons, also displayed enhanced drug-induced SWDs and absence seizures. On the other hand, tonic firing in the TRN was increased in these mice, suggesting that increased tonic firing in the TRN may be sufficient for druginduced SWD generation in the absence of burst firing. These results call into question the role of burst firing in TRN neurons in the genesis of SWDs, calling for a rethinking of the mechanism for absence seizure induction.
UR - http://www.scopus.com/inward/record.url?scp=84905967103&partnerID=8YFLogxK
U2 - 10.1073/pnas.1408609111
DO - 10.1073/pnas.1408609111
M3 - Article
C2 - 25071191
AN - SCOPUS:84905967103
SN - 0027-8424
VL - 111
SP - 11828
EP - 11833
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 32
ER -