NORADRENERGIC REGULATION OF SYNAPTIC INHIBITION

海马区的突触生理学的特点是强烈的局部 兴奋性突触对抑制回路的影响 变速箱。神经递质去甲肾上腺素(NE) 突触抑制在海马区有两条重要途径。在以下时间行事 去甲肾上腺素受体，NE产生去抑制，减少刺激- 通过一种未知的作用诱发抑制性突触后电位 抑制性中间神经元。它还通过以下方式增加紧张性突触抑制 直接刺激中间神经元的动作电位放电。两个都是 这些行动可能参与了众所周知但鲜为人知的 去甲肾上腺素降低癫痫发作的作用例如54，55。在这里，我们提出一种 深入研究去甲肾上腺素的去抑制作用，以确定其 潜在的生理机制。拟议的研究将 集中在去甲肾上腺素对海马神经元的作用；以前， 我们已经确定了三种可能是肾上腺素能的基础机制 去抑制；阻断兴奋性突触激活 Oreens/Alveus中间神经元，这些中间神经元的直接去极化， 导致失去反应性，并导致腔隙超极化- 分子间神经元，导致远端慢抑制的丧失 海马区的CA1区。实验的目的将是确定 这些影响的机制以及理解它们在控制中的作用 海马区兴奋性。

Synaptic physiology in the hippocampus is characterized by strong local inhibitory circuits that the influence of excitatory synaptic transmission. The neurotransmitter norepinephrine (NE), regulates synaptic inhibition in the hippocampus in two important ways. Acting at alpha adrenoceptors, NE produces disinhibition, a reduction in stimulus- evoked inhibitory postsynaptic potentials, through an unknown action on inhibitory interneurons. It also increases tonic synaptic inhibition by directly stimulating action potential discharge in interneurons. Both of these actions may participate in the well-known, but poorly understood, action of NE to reduce epileptic activity eg 54,55. Here we propose a thorough examination of the disinhibitory action of NE, to define its underlying physiological mechanisms. The proposed studies will concentrate on the actions of NE on hippocampal interneurons; Previously, we have identified three mechanisms that may underlie adrenergic disinhibition; Blockade of excitatory synaptic activation of oriens/alveus interneurons, direct depolarization of these interneurons, leading to loss of responsiveness, and, hyperpolarization of lacunosum- molecular interneurons, leading to a loss of distal slow inhibition in area CA1 of the hippocampus. Experiments will be directed at determining a mechanism for these effects and understanding their role in controlling hippocampal excitability.