TY - JOUR
T1 - AMPAR-independent effect of striatal αCaMKII promotes the sensitization of cocaine reward
AU - Kourrich, Saïd
AU - Klug, Jason R.
AU - Mayford, Mark
AU - Thomas, Mark J.
PY - 2012/5/9
Y1 - 2012/5/9
N2 - Changes in CaMKII-regulated synaptic excitability are a means through which experience may modify neuronal function and shape behavior. While behavior in rodent addiction models is linked with CaMKII activity in the nucleus accumbens (NAc) shell, the key cellular adaptations that forge this link are unclear. Using a mouse strain with striatal-specific expression of autonomously active CaMKII (T286D), we demonstrate that while persistent CaMKII activity induces behaviors comparable to those in mice repeatedly exposed to psychostimulants, it is insufficient to increase AMPAR-mediated synaptic strength in NAc shell. However, autonomous CaMKII up regulates A-type K + current (IA) and decreases firing in shell neurons. Importantly, inactivating the transgene with doxycycline eliminates both the IA-mediated firing decrease and the elevated behavioral response to cocaine. This study identifies CaMKII regulation of IA in NAc shell neurons as a novel cellular contributor to the sensitization of cocaine reward.
AB - Changes in CaMKII-regulated synaptic excitability are a means through which experience may modify neuronal function and shape behavior. While behavior in rodent addiction models is linked with CaMKII activity in the nucleus accumbens (NAc) shell, the key cellular adaptations that forge this link are unclear. Using a mouse strain with striatal-specific expression of autonomously active CaMKII (T286D), we demonstrate that while persistent CaMKII activity induces behaviors comparable to those in mice repeatedly exposed to psychostimulants, it is insufficient to increase AMPAR-mediated synaptic strength in NAc shell. However, autonomous CaMKII up regulates A-type K + current (IA) and decreases firing in shell neurons. Importantly, inactivating the transgene with doxycycline eliminates both the IA-mediated firing decrease and the elevated behavioral response to cocaine. This study identifies CaMKII regulation of IA in NAc shell neurons as a novel cellular contributor to the sensitization of cocaine reward.
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U2 - 10.1523/JNEUROSCI.6391-11.2012
DO - 10.1523/JNEUROSCI.6391-11.2012
M3 - Article
C2 - 22573680
AN - SCOPUS:84860656141
SN - 0270-6474
VL - 32
SP - 6578
EP - 6586
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 19
ER -