TY - JOUR
T1 - Deletion of N-type Ca2+ channel Cav2.2 results in hyperaggressive behaviors in mice
AU - Kim, Chanki
AU - Jeon, Daejong
AU - Kim, Young Hoon
AU - Lee, C. Justin
AU - Kim, Hyun
AU - Shin, Hee Sup
PY - 2009/1/30
Y1 - 2009/1/30
N2 - Voltage-dependent N-type Ca2+ channels play important roles in the regulation of diverse neuronal functions in the brain, but little is known about its role in social aggressive behaviors. Mice lacking the α1B subunit (Cav2.2) of N-type Ca2+ channels showed markedly enhanced aggressive behaviors to an intruder mouse in the resident-intruder test. The dorsal raphe nucleus (DRN), which contains serotonin neurons, is known to be involved in aggression in animals. We thus examined the DRN neurons in the Cav2.2-deficient (Cav2.2-/-) mice. Microinjection of ω-conotoxin GVIA, an N-type Ca2+ channel-specific blocker, into the DRN of wild type mice resulted in escalated aggression, mimicking the phenotypes of Cav2.2-/-. Electrophysiological analysis showed increased firing activity of serotonin neurons with a reduced inhibitory neurotransmission in the Ca v2.2-/- DRN. Cav2.2-/- mice showed an elevated level of arginine vasopressin, an aggression-related hormone, in the cerebrospinal fluid. In addition, Cav2.2-/- mice showed an increase of serotonin in the hypothalamus. These results suggest that N-type Ca2+ channels at the DRN have a key role in the control of aggression.
AB - Voltage-dependent N-type Ca2+ channels play important roles in the regulation of diverse neuronal functions in the brain, but little is known about its role in social aggressive behaviors. Mice lacking the α1B subunit (Cav2.2) of N-type Ca2+ channels showed markedly enhanced aggressive behaviors to an intruder mouse in the resident-intruder test. The dorsal raphe nucleus (DRN), which contains serotonin neurons, is known to be involved in aggression in animals. We thus examined the DRN neurons in the Cav2.2-deficient (Cav2.2-/-) mice. Microinjection of ω-conotoxin GVIA, an N-type Ca2+ channel-specific blocker, into the DRN of wild type mice resulted in escalated aggression, mimicking the phenotypes of Cav2.2-/-. Electrophysiological analysis showed increased firing activity of serotonin neurons with a reduced inhibitory neurotransmission in the Ca v2.2-/- DRN. Cav2.2-/- mice showed an elevated level of arginine vasopressin, an aggression-related hormone, in the cerebrospinal fluid. In addition, Cav2.2-/- mice showed an increase of serotonin in the hypothalamus. These results suggest that N-type Ca2+ channels at the DRN have a key role in the control of aggression.
UR - http://www.scopus.com/inward/record.url?scp=59149098711&partnerID=8YFLogxK
U2 - 10.1074/jbc.M807179200
DO - 10.1074/jbc.M807179200
M3 - Article
C2 - 19004821
AN - SCOPUS:59149098711
SN - 0021-9258
VL - 284
SP - 2738
EP - 2745
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -