Differential modulation of nucleus accumbens synapses
Differential modulation of nucleus accumbens synapses
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DOI：
10.1152/jn.00766.2001
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发表时间：
2002-07-01
影响因子：
2.5
通讯作者：
Williams, JT
中科院分区：
文献类型：
--
作者：
Brundege, JM;Williams, JT
伏隔核（NAcc）是一个大脑区域，涉及从动机和奖励到进食和药物成瘾等功能。 NAcc 通常分为两个主要部分：外壳和核心。这两个区域的主要输出神经元都是中棘神经元（MSN），它们在休息时处于静止状态，并依赖于兴奋性和抑制性突触的相对输入来确定它们何时激发动作电位。这些突触输入反过来又受到许多神经化学信号剂的调节，这些信号剂最终可以影响 NAcc 中的信息处理。本研究描述了 NAcc MSN 中三种主要信号传导途径调节突触传递的能力，并比较了 NAcc 内不同突触的这种调节。阿片类药物 [Met]5 脑啡肽 (ME) 抑制壳 MSN 中的兴奋性突触后电流 (EPSC)，这种作用主要由 mu-阿片类受体介导。 Forskolin 是一种腺苷酸环化酶激活剂，可增强壳 EPSC。对微型 EPSC 的分析表明主要是突触前的作用位点，尽管较小的突触后效应也可能有助于增强作用。腺苷和腺苷 A(1) 受体激动剂抑制壳 EPSC，但未检测到内源腺苷的显着强直抑制作用。然后在 NAcc 中的四种不同突触中比较这些信号剂的作用：核心和外壳亚区域的谷氨酸能 EPSC 和 GABA 能抑制性突触后电流 (IPSC)。 ME 抑制所有这四种突触，但对壳 IPSC 的抑制作用明显强于其他突触。毛喉素使每个测试的突触的传递增加。然而，与壳微型 EPSC 相比，对壳中微型 IPSC 的分析显示，没有迹象表明突触后对这种增强有贡献。内源性腺苷对突触电流的强直抑制作用在壳 EPSC 中未观察到，但在其他三个测试的突触中明显存在。这些结果表明，神经调节在 NAcc 的不同子区域之间以及每个子区域内的不同突触之间可能会有所不同。这可能反映了亚区域之间神经元互连和功能作用的差异，并可能有助于药物作用于这些系统的效果。
The nucleus accumbens (NAcc) is a brain region involved in functions ranging from motivation and reward to feeding and drug addiction. The NAcc is typically divided into two major subdivisions, the shell and the core. The primary output neurons of both of these areas are medium spiny neurons (MSNs), which are quiescent at rest and depend on the relative input of excitatory and inhibitory synapses to determine when they fire action potentials. These synaptic inputs are, in turn, regulated by a number of neurochemical signaling agents that can ultimately influence information processing in the NAcc. The present study characterized the ability of three major signaling pathways to modulate synaptic transmission in NAcc MSNs and compared this modulation across different synapses within the NAcc. The opioid [Met] 5 enkephalin (ME) inhibited excitatory postsynaptic currents (EPSCs) in shell MSNs, an effect mediated primarily by mu-opioid receptors. Forskolin, an activator of adenylyl cyclase, potentiated shell EPSCs. An analysis of miniature EPSCs indicated a primarily presynaptic site of action, although a smaller postsynaptic effect may have also contributed to the potentiation. Adenosine and an adenosine A(1)-receptor agonist inhibited shell EPSCs, although no significant tonic inhibition by endogenous adenosine was detected. The effects of these signaling agents were then compared across four different synapses in the NAcc: glutamatergic EPSCs and GABAergic inhibitory postsynaptic currents (IPSCs) in both the core and shell subregions. ME inhibited all four of these synapses but produced a significantly greater inhibition of shell IPSCs than the other synapses. Forskolin produced an increase in transmission at each of the synapses tested. However, analysis of miniature IPSCs in the shell showed no sign of a postsynaptic contribution to this potentiation, in contrast to the shell miniature EPSCs. Tonic inhibition of synaptic currents by endogenous adenosine, which was not observed in shell EPSCs, was clearly present at the other three synapses tested. These results indicate that neuromodulation can vary between the different subregions of the NAcc and between the different synapses within each subregion. This may reflect differences in neuronal interconnections and functional roles between subregions and may contribute to the effects of drugs acting on these systems.