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Postsynaptic excitation of prefrontal cortical pyramidal neurons by hypocretin‐1/orexin a through the inhibition of potassium currents
Author(s) -
Xia Jianxia,
Chen Xiaowei,
Song Chenghui,
Ye Jianning,
Yu Zhengping,
Hu Zhian
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20667
Subject(s) - excitatory postsynaptic potential , neuroscience , postsynaptic potential , inhibitory postsynaptic potential , chemistry , postsynaptic current , wakefulness , orexin , biology , neuropeptide , receptor , electroencephalography , biochemistry
Abstract Hypocretins are crucial for the regulation of wakefulness by the excitatory actions on multiple subcortical arousal systems. To date, there is little information about the direct postsynaptic excitatory effects of hypocretins on the neurons in prefrontal cortex (PFC), which is important for higher cognitive functions and is correlated with level of wakefulness. In this study, we tested the excitatory effects of hypocretin‐1 on acutely isolated PFC pyramidal neurons of rats and studied the possible ionic mechanisms by using whole‐cell patch‐clamp techniques. Puff application of hypocretin‐1 caused a dose‐dependent excitation. Further observations that perfusion of Ca 2+ ‐free artificial cerebrospinal fluid did not influence the depolarizing effects of hypocretin‐1, in conjunction with the findings that hypocretin‐1 could decrease net whole‐cell K + currents, demonstrate that the excitatory effects of hypocretin‐1 on PFC neurons are mediated by the inhibition of K + currents but not Ca 2+ influx. Finally, the decrease in K + currents induced by hypocretin‐1 was abolished by a protein kinase C (PKC) inhibitor (BIS II) or a phospholipase C (PLC) inhibitor (D609), suggesting that PKC and PLC appear to be involved in mediating the inhibitory effects of hypocretin‐1 on K + currents. These results indicate that hypocretin‐1 exerts a postsynaptic excitatory action on PFC neurons through the inhibition of K + currents, which probably results from activation of PKC and PLC signaling pathways. © 2005 Wiley‐Liss, Inc.