Rosenkranz J Amiel, Johnston Daniel
Center for Learning and Memory, University of Texas, Austin, Texas 78712, USA.
J Neurosci. 2006 Mar 22;26(12):3229-44. doi: 10.1523/JNEUROSCI.4333-05.2006.
The entorhinal cortex (EC) is a significant component of the systems that underlie certain forms of memory formation and recall. Evidence has been emerging that the dopaminergic system in the EC facilitates these and other functions of the EC. The effects of dopamine (DA) on membrane properties and excitability of EC neurons, however, are not known. We used in vitro whole-cell patch-clamp recordings from layer V pyramidal neuronal somata and dendrites of the adult rat lateral EC to investigate the effects of DA on the excitability of these neurons. We found that brief application of DA caused a reduction in the excitability of layer V EC pyramidal neurons. This effect was attributable to voltage-dependent modification of membrane properties that can best be explained by an increase in a hyperpolarization-activated conductance. Furthermore, the effects of DA were blocked by pharmacological blockade of h-channels, but not by any of a number of other ion channels. These actions were produced by a D1 receptor-mediated increase of cAMP but were independent of protein kinase A. A portion of the actions of DA can be attributed to effects in the apical dendrites. The data suggest that DA can directly influence the membrane properties of layer V EC pyramidal neurons by modulation of h-channels. These actions may underlie some of the effects of DA on memory formation.
内嗅皮质(EC)是某些形式的记忆形成和回忆所依赖系统的重要组成部分。越来越多的证据表明,EC中的多巴胺能系统促进了EC的这些及其他功能。然而,多巴胺(DA)对EC神经元膜特性和兴奋性的影响尚不清楚。我们使用成年大鼠外侧EC第V层锥体神经元胞体和树突的体外全细胞膜片钳记录来研究DA对这些神经元兴奋性的影响。我们发现,短暂应用DA会导致第V层EC锥体神经元的兴奋性降低。这种效应归因于膜特性的电压依赖性改变,这可以通过超极化激活电导的增加得到最好的解释。此外,DA的效应可被h通道的药理学阻断所阻断,但不能被许多其他离子通道中的任何一种阻断。这些作用是由D1受体介导的cAMP增加产生的,但与蛋白激酶A无关。DA的一部分作用可归因于其对顶端树突的影响。数据表明,DA可通过调节h通道直接影响第V层EC锥体神经元的膜特性。这些作用可能是DA对记忆形成产生某些影响的基础。