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内在电压动力学控制基底前脑非胆碱能神经元自发放电模式的多样性。

Intrinsic voltage dynamics govern the diversity of spontaneous firing profiles in basal forebrain noncholinergic neurons.

机构信息

Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey, USA.

出版信息

J Neurophysiol. 2012 Jul;108(2):406-18. doi: 10.1152/jn.00642.2011. Epub 2012 Apr 11.

Abstract

Spontaneous firing and behavior-related changes in discharge profiles of basal forebrain (BF) neurons are well documented, albeit the mechanisms underlying the variety of activity modes and intermodal transitions remain elusive. With the use of cell-attached recordings, this study identifies a range of spiking patterns in diagonal band Broca (DBB) noncholinergic cells of rats and tentatively categorizes them into low-rate random, tonic, and cluster firing activities. It demonstrates further that the multiplicity of discharge profiles is sustained intrinsically and persists after blockade of glutamate-, glycine/GABA-, and cholinergic synaptic inputs. Stimulation of muscarinic receptors, blockade of voltage-gated Ca(2+)-, and small conductance (SK) Ca(2+)-activated K(+) currents as well as chelating of intracellular Ca(2+) concentration accelerate low-rate random and tonic firing and favor transition of neurons into cluster firing mode. A similar trend towards higher discharge rates with switch of neurons into cluster firing has been revealed by activation of neuropeptide Y (NPY) receptors with the NPY or NPY(1) receptor agonist [Leu(31),Pro(34)]-NPY. Whole cell current-clamp analysis demonstrates that the variety of spiking modes and intermodal transitions could be induced within the same neuronal population by injection of bias depolarizing or hyperpolarizing currents. Taken together, these data demonstrate the intrinsic and highly variable character of regenerative firing in BF noncholinergic cells, subject to powerful modulation by classical neurotransmitters, NPY, and small membrane currents.

摘要

基底前脑 (BF) 神经元的自发放电和与行为相关的放电模式变化已有大量记录,但活动模式的多样性和模态间转换的机制仍不清楚。本研究使用细胞贴附记录技术,在大鼠斜角带 Broca (DBB) 非胆碱能细胞中识别出一系列的放电模式,并初步将其分为低频率随机、紧张性和簇状放电活动。进一步表明,放电模式的多样性是内在维持的,并且在阻断谷氨酸、甘氨酸/ GABA 和胆碱能突触输入后仍然存在。刺激毒蕈碱受体、阻断电压门控 Ca(2+) 和小电导 (SK) Ca(2+) 激活的 K(+) 电流以及螯合细胞内 Ca(2+) 浓度会加速低频率随机和紧张性放电,并有利于神经元向簇状放电模式转换。通过用 NPY 或 NPY(1) 受体激动剂 [Leu(31),Pro(34)]-NPY 激活神经肽 Y (NPY) 受体,揭示了神经元向簇状放电转换时更高放电率的类似趋势。全细胞膜片钳分析表明,通过注入偏置去极化或超极化电流,可以在同一神经元群体中诱导多种放电模式和模态间转换。总之,这些数据表明 BF 非胆碱能细胞的再生性放电具有内在的和高度可变性的特征,受到经典神经递质、NPY 和小膜电流的强大调制。

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