Chung Leeyup, Moore Scott D, Cox Charles L
Neuroscience Program, Beckman Institute, University of Illinois, Urbana, IL 61801, USA.
Brain Res. 2009 Jul 28;1282:10-9. doi: 10.1016/j.brainres.2009.05.061. Epub 2009 Jun 2.
Layer 6b in neocortex is a distinct sublamina at the ventral portion of layer 6. Corticothalamic projections arise from 6b neurons, but few studies have examined the functional properties of these cells. In the present study we examined the actions of cholecystokinin (CCK) on layer 6b neocortical neurons using whole-cell patch clamp recording techniques. We found that the general CCK receptor agonist CCK8S (sulfated CCK octapeptide) strongly depolarized the neurons, and this action persisted in the presence of tetrodotoxin, suggesting a postsynaptic site of action. The excitatory actions of CCK8S were mimicked by the selective CCK(B) receptor agonist CCK4, and attenuated by the selective CCK(B) receptor antagonist L365260, indicating a role for CCK(B) receptors. Voltage-clamp recordings revealed that CCK8S produced a slow inward current associated with a decreased conductance with a reversal potential near the K(+) equilibrium potential. In addition, intracellular cesium also blocked the inward current, suggesting the involvement of a K(+) conductance, likely K(leak). Our data indicate that CCK, acting via CCK(B) receptors, produces a long-lasting excitation of layer 6b neocortical neurons, and this action may play a critical role in modulation of corticothalamic circuit activity.
新皮层的6b层是第6层腹侧的一个独特亚层。皮质丘脑投射起源于6b层神经元,但很少有研究考察这些细胞的功能特性。在本研究中,我们使用全细胞膜片钳记录技术研究了胆囊收缩素(CCK)对新皮层6b层神经元的作用。我们发现,CCK的一般受体激动剂CCK8S(硫酸化CCK八肽)使神经元强烈去极化,并且在存在河豚毒素时这种作用仍然持续,提示其作用位点在突触后。CCK8S的兴奋作用被选择性CCK(B)受体激动剂CCK4模拟,并被选择性CCK(B)受体拮抗剂L365260减弱,表明CCK(B)受体起作用。电压钳记录显示,CCK8S产生一个缓慢内向电流,伴有电导降低,反转电位接近K(+)平衡电位。此外,细胞内铯也阻断内向电流,提示涉及一个K(+)电导,可能是K(漏)。我们的数据表明,CCK通过CCK(B)受体起作用,对新皮层6b层神经元产生持久兴奋,并且这种作用可能在调节皮质丘脑回路活动中起关键作用。