TY - JOUR T1 - Countervailing Modulation of <em>I</em><sub>h</sub> by Neuropeptide Y and Corticotrophin-Releasing Factor in Basolateral Amygdala As a Possible Mechanism for Their Effects on Stress-Related Behaviors JF - The Journal of Neuroscience JO - J. Neurosci. SP - 16970 LP - 16982 DO - 10.1523/JNEUROSCI.2306-10.2010 VL - 30 IS - 50 AU - Chantelle J. Giesbrecht AU - James P. Mackay AU - Heika B. Silveira AU - Janice H. Urban AU - William F. Colmers Y1 - 2010/12/15 UR - http://www.jneurosci.org/content/30/50/16970.abstract N2 - Stress and anxiety-related behaviors controlled by the basolateral amygdala (BLA) are regulated in vivo by neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF): NPY produces anxiolytic effects, whereas CRF produces anxiogenic effects. These opposing actions are likely mediated via regulation of excitatory output from the BLA to afferent targets. In these studies, we examined mechanisms underlying the effects of NPY and CRF in the BLA using whole-cell patch-clamp electrophysiology in rat brain slices. NPY, even with tetrodotoxin present, caused a dose-dependent membrane hyperpolarization in BLA pyramidal neurons. The hyperpolarization resulted in the inhibition of pyramidal cells, despite arising from a reduction in a voltage-dependent membrane conductance. The Y1 receptor agonist, F7P34 NPY, produced a similar membrane hyperpolarization, whereas the Y1 antagonist, BIBO3304 [(R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N2-(diphenylacetyl)-argininamide trifluoroacetate], blocked the effect of NPY. The NPY-inhibited current was identified as Ih, which is active at and hyperpolarized to rest. Responses to NPY were occluded by either Cs+ or ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride), but unaffected by the GIRK-preferring blockers Ba2+ and SCH23390 [(R)-(+)-7-chloro-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride]. Application of CRF, with or without TTX present, depolarized NPY-sensitive BLA pyramidal neurons, resulting from an increase in Ih. Electrophysiological and immunocytochemical data were consistent with a major role for the HCN1 subunit. Our results indicate that NPY, via Y1 receptors, directly inhibits BLA pyramidal neurons by suppressing a postsynaptic Ih, whereas CRF enhances resting Ih, causing an increased excitability of BLA pyramidal neurons. The opposing actions of these two peptides on the excitability of BLA output cells are consistent with the observed behavioral actions of NPY and CRF in the BLA. ER -