TY - JOUR
T1 - Et tu, CA2
T2 - CA2 Is Hyperexcitable and Controls Seizures in a Mouse Model of Temporal Lobe Epilepsy
AU - Shuman, Tristan
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Enhanced Excitability of the Hippocampal CA2 Region and Its Contribution to Seizure Activity in a Mouse Model of Temporal Lobe Epilepsy Whitebirch AC, LaFrancois JJ, Jain S, Leary P, Santoro B, Siegelbaum SA, Scharfman HE. Neuron. 2022;110(19):3121-3138. doi:10.1016/j.neuron.2022.07.020. PMID: 35987207 The hippocampal CA2 region, an area important for social memory, has been suspected to play a role in temporal lobe epilepsy (TLE) because of its resistance to degeneration observed in neighboring CA1 and CA3 regions in both humans and rodent models of TLE. However, little is known about whether alterations in CA2 properties promote seizure generation or propagation. Here, we addressed the role of CA2 using the pilocarpine-induced status epilepticus model of TLE. Ex vivo electrophysiological recordings from acute hippocampal slices revealed a set of coordinated changes that enhance CA2 PC intrinsic excitability, reduce CA2 inhibitory input, and increase CA2 excitatory output to its major CA1 synaptic target. Moreover, selective chemogenetic silencing of CA2 pyramidal cells caused a significant decrease in the frequency of spontaneous seizures measured in vivo. These findings provide the first evidence that CA2 actively contributes to TLE seizure activity and may thus be a promising therapeutic target.
AB - Enhanced Excitability of the Hippocampal CA2 Region and Its Contribution to Seizure Activity in a Mouse Model of Temporal Lobe Epilepsy Whitebirch AC, LaFrancois JJ, Jain S, Leary P, Santoro B, Siegelbaum SA, Scharfman HE. Neuron. 2022;110(19):3121-3138. doi:10.1016/j.neuron.2022.07.020. PMID: 35987207 The hippocampal CA2 region, an area important for social memory, has been suspected to play a role in temporal lobe epilepsy (TLE) because of its resistance to degeneration observed in neighboring CA1 and CA3 regions in both humans and rodent models of TLE. However, little is known about whether alterations in CA2 properties promote seizure generation or propagation. Here, we addressed the role of CA2 using the pilocarpine-induced status epilepticus model of TLE. Ex vivo electrophysiological recordings from acute hippocampal slices revealed a set of coordinated changes that enhance CA2 PC intrinsic excitability, reduce CA2 inhibitory input, and increase CA2 excitatory output to its major CA1 synaptic target. Moreover, selective chemogenetic silencing of CA2 pyramidal cells caused a significant decrease in the frequency of spontaneous seizures measured in vivo. These findings provide the first evidence that CA2 actively contributes to TLE seizure activity and may thus be a promising therapeutic target.
UR - http://www.scopus.com/inward/record.url?scp=85146736349&partnerID=8YFLogxK
U2 - 10.1177/15357597221150068
DO - 10.1177/15357597221150068
M3 - Comment/debate
AN - SCOPUS:85146736349
SN - 1535-7597
VL - 23
SP - 121
EP - 123
JO - Epilepsy Currents
JF - Epilepsy Currents
IS - 2
ER -