NORADRENERGIC REGULATION OF SYNAPTIC INHIBITION

海马体中的突触生理学的特征是强烈的局部 兴奋性突触影响的抑制回路 传输 神经递质去甲肾上腺素（NE），调节 海马区的突触抑制有两个重要方面。 作用在 α肾上腺素受体，NE产生去抑制，减少刺激- 诱发抑制性突触后电位，通过一个未知的行动， 抑制性中间神经元 它还增加强直性突触抑制， 直接刺激中间神经元的动作电位放电。 两 这些行动可能参与众所周知，但知之甚少， NE减少癫痫活动的作用如54、55。 在这里我们提出了一个 彻底检查NE的去抑制作用，以确定其 潜在的生理机制 拟议的研究将 集中于NE对海马中间神经元的作用;以前， 我们已经确定了三种机制， 兴奋性突触激活的阻断 方向/肺泡中间神经元，这些中间神经元的直接去极化， 导致反应性丧失和腔隙超极化- 分子中间神经元，导致远端缓慢抑制的损失， 海马CA 1区 实验的目的是确定 这些影响的机制，并了解它们在控制 海马兴奋性

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.