Disrupted activity in the hippocampal-accumbens circuit of type III neuregulin 1 mutant mice.
Disrupted activity in the hippocampal-accumbens circuit of type III neuregulin 1 mutant mice.
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DOI：
10.1038/npp.2010.180
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发表时间：
2011-01
期刊：
影响因子：
--
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中科院分区：
文献类型：
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神经调节蛋白1 （Nrg1）是一种精神分裂症易感基因，参与神经发育的基本方面。缺乏几种Nrg1亚型中的任何一种的小鼠具有多种与精神分裂症相关的表型，包括工作记忆和感觉运动门控缺陷，腹侧下托锥体神经元棘缺失，皮质锥体细胞树突缺失，前额皮质小蛋白阳性中间神经元缺失，皮质边缘突触可塑性改变；Nrg1基因外显子7断裂的杂合小鼠缺乏iii型（含富含半胱氨酸结构域）同工型，并且具有感觉运动门控缺陷，可能涉及从腹侧海马（vHPC）到伏隔核（nACC）中棘神经元的投射回路活动的变化。为了探索这些缺陷的神经基础，我们检测了这些小鼠nACC和vHPC的电生理活动。在氨基甲酸乙酯麻醉下，野生型和突变型小鼠的自发性活动爆发从vHPC传播到nACC。然而，这些脉冲在突变体nACC中较弱，局部场电位振幅和峰值活性降低。突变型nACC的单个单位在脉冲内发射频率较低，而在脉冲外发射频率较高。此外，脉冲内的nACC尖峰较少受到vHPC活动的调制，这是由脉冲低频振荡成分的锁相决定的。这些数据表明，在III型Nrg1杂合子中，vHPC输入nACC的功效降低，支持Nrg1在海马-伏隔突触功能谱中的作用。
Neuregulin 1 (Nrg1), a schizophrenia susceptibility gene, is involved in fundamental aspects of neurodevelopment. Mice lacking any one of several isoforms of Nrg1 have a variety of schizophrenia-related phenotypes, including deficits in working memory and sensorimotor gating, loss of spines in pyramidal neurons in the ventral subiculum, loss of dendrites in cortical pyramidal cells, loss of parvalbumin-positive interneurons in the prefrontal cortex, and altered plasticity in cortico-limbic synapses;. Mice heterozygous for a disruption in exon 7 of the Nrg1 genelack Type-III (cysteine-rich domain-containing) isoforms and have sensorimotor gating deficits that may involve changes in the activity of a circuit involving projections from the ventral hippocampus (vHPC) to medium spiny neurons in the nucleus accumbens (nACC). To explore the neural basis of these deficits, we examined electrophysiological activity in the nACC and vHPC of these mice. Under urethane anesthesia, bursts of spontaneous activity propagated from the vHPC to the nACC in both wild-type and mutant mice. However, these bursts were weaker in mutant nACC, with reduced local field potential amplitude and spiking activity. Single units in mutant nACC fired less frequently within the bursts, and more frequently outside of the bursts. Moreover, within-burst nACC spiking was less modulated by vHPC activity, as determined by phase-locking to the low-frequency oscillatory components of the bursts. These data suggest that the efficacy of vHPC input to the nACC is reduced in the Type III Nrg1 heterozygotes, supporting a role for Nrg1 in the functional profile of hippocampal-accumbens synapses.
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DOI：
10.1523/jneurosci.1815-08.2008
发表时间：
2008-07-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen YJ;Johnson MA;Lieberman MD;Goodchild RE;Schobel S;Lewandowski N;Rosoklija G;Liu RC;Gingrich JA;Small S;Moore H;Dwork AJ;Talmage DA;Role LW
通讯作者：
Role LW
影响因子：
10.6
作者：
Moore, Holly;Jentsch, J. David;Grace, Anthony A.
通讯作者：
Grace, Anthony A.
影响因子：
7.8
作者：
Bao, JX;Wolpowitz, D;Role, LW;Talmage, DA
通讯作者：
Talmage, DA
影响因子：
3.5
作者：
Li, Dawei;Collier, David A.;He, Lin
通讯作者：
He, Lin
影响因子：
2.5
作者：
French, SJ;Totterdell, S
通讯作者：
Totterdell, S