Stackman R W, Walsh T J, Brucato F H, Swartzwelder H S
Department of Psychology, Rutgers University, New Brunswick, NJ 08903, USA.
Brain Res. 1996 Apr 22;717(1-2):12-21. doi: 10.1016/0006-8993(95)01455-1.
Infusion of benzodiazepine (BDZ) receptor ligands into the medial septum (MS) produces a bidirectional modulation of spatial memory retention. The present experiments sought to determine the effects of BDZ ligands upon synaptic responses and long-term potentiation (LTP) in the dentate gyrus following electrical stimulation of the angular bundle. Intraseptal infusion of the BDZ agonist, chlordiazepoxide, decreased the amplitude of the evoked population spike and increased paired-pulse facilitation at a 150-ms interstimulus interval (ISI) in a dose-dependent manner. Intraseptal infusion of the BDZ antagonist, flumazenil (10 nmol), enhanced the amplitude of the dentate population spike and also increased paired-pulse facilitation at the 150-ms ISI. There was no effect of either BDZ receptor ligand upon the slope of the rising phase of the evoked population excitatory postsynaptic potential (pEPSP). Intraseptal flumazenil also significantly enhanced the magnitude of dentate LTP induced by high-frequency stimulation of the angular bundle. Intraseptal chlordiazepoxide failed to alter LTP induction. These results indicate that intraseptal infusion of an amnestic dose of the BDZ ligand, chlordiazepoxide, decreases the excitatory responsiveness of the dentate gyrus to its synaptic input from entorhinal cortex. In contrast, the promnestic BDZ ligand, flumazenil, enhances dentate granule cell responsivity, and facilitates synaptic plasticity in the dentate gyrus network. Taken together these data suggest that the memory impairing and memory enhancing action of these compounds may be a function of their ability to alter hippocampal physiology during a critical phase of memory. The potential role of septodentate cholinergic and GABAergic projections in the present observation is discussed.
向内侧隔区（MS）注入苯二氮䓬（BDZ）受体配体可对空间记忆保持产生双向调节作用。本实验旨在确定BDZ配体对角束电刺激后齿状回突触反应和长时程增强（LTP）的影响。向隔区内注入BDZ激动剂氯氮䓬，可剂量依赖性地降低诱发群体峰电位的幅度，并在150毫秒的刺激间隔（ISI）时增加双脉冲易化。向隔区内注入BDZ拮抗剂氟马西尼（10纳摩尔），可增强齿状回群体峰电位的幅度，并在150毫秒的ISI时增加双脉冲易化。两种BDZ受体配体对诱发群体兴奋性突触后电位（pEPSP）上升相的斜率均无影响。隔区内注入氟马西尼还显著增强了角束高频刺激诱导的齿状回LTP的幅度。隔区内注入氯氮䓬未能改变LTP的诱导。这些结果表明，向隔区内注入失忆剂量的BDZ配体氯氮䓬，可降低齿状回对来自内嗅皮质突触输入的兴奋性反应。相反，具有促记忆作用的BDZ配体氟马西尼可增强齿状回颗粒细胞的反应性，并促进齿状回网络中的突触可塑性。综合这些数据表明，这些化合物的记忆损害和记忆增强作用可能与其在记忆关键阶段改变海马生理功能的能力有关。本文还讨论了隔区-齿状回胆碱能和GABA能投射在本观察中的潜在作用。
