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新生大鼠脑片蓝斑中的自分泌神经调节与网络活动模式

Autocrine Neuromodulation and Network Activity Patterns in the Locus Coeruleus of Newborn Rat Slices.

作者信息

Waselenchuk Quinn, Ballanyi Klaus

机构信息

Department of Physiology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.

出版信息

Brain Sci. 2022 Mar 25;12(4):437. doi: 10.3390/brainsci12040437.

Abstract

Already in newborns, the locus coeruleus (LC) controls multiple brain functions and may have a complex organization as in adults. Our findings in newborn rat brain slices indicate that LC neurons (i) generate at ~1 Hz a ~0.3 s-lasting local field potential (LFP) comprising summated phase-locked single spike discharge, (ii) express intrinsic ‘pacemaker’ or ‘burster’ properties and (iii) receive solely excitatory or initially excitatory−secondary inhibitory inputs. μ-opioid or ɑ2 noradrenaline receptor agonists block LFP rhythm at 100−250 nM whereas slightly lower doses transform its bell-shaped pattern into slower crescendo-shaped multipeak bursts. GABAA and glycine receptors hyperpolarize LC neurons to abolish rhythm which remains though unaffected by blocking them. Rhythm persists also during ionotropic glutamate receptor (iGluR) inhibition whereas <10 mV depolarization during iGluR agonists accelerates spiking to cause subtype-specific fast (spindle-shaped) LFP oscillations. Similar modest neuronal depolarization causing a cytosolic Ca2+ rise occurs (without effect on neighboring astrocytes) during LFP acceleration by CNQX activating a TARP-AMPA-type iGluR complex. In contrast, noradrenaline lowers neuronal Ca2+ baseline via ɑ2 receptors, but evokes an ɑ1 receptor-mediated ‘concentric’ astrocytic Ca2+ wave. In summary, the neonatal LC has a complex (possibly modular) organization to enable discharge pattern transformations that might facilitate discrete actions on target circuits.

摘要

早在新生儿期,蓝斑(LC)就控制着多种脑功能,其组织结构可能与成年人一样复杂。我们在新生大鼠脑片中的研究结果表明,LC神经元(i)以约1 Hz的频率产生持续约0.3秒的局部场电位(LFP),该电位由总和的锁相单峰放电组成;(ii)表现出内在的“起搏器”或“爆发器”特性;(iii)仅接受兴奋性或最初兴奋性-继发性抑制性输入。μ-阿片受体或α2去甲肾上腺素受体激动剂在100-250 nM时阻断LFP节律,而略低剂量则将其钟形模式转变为较慢的渐强形多峰爆发。GABAA和甘氨酸受体使LC神经元超极化以消除节律,但阻断这些受体时节律不受影响。在离子型谷氨酸受体(iGluR)抑制期间节律仍然存在,而在iGluR激动剂作用下<10 mV的去极化会加速放电,导致亚型特异性的快速(纺锤形)LFP振荡。在通过CNQX激活TARP-AMPA型iGluR复合物使LFP加速期间,会发生类似的适度神经元去极化,导致胞质Ca2+升高(对相邻星形胶质细胞无影响)。相比之下,去甲肾上腺素通过α2受体降低神经元Ca2+基线,但会引发α1受体介导的“同心”星形胶质细胞Ca2+波。总之,新生儿LC具有复杂的(可能是模块化的)组织结构,以实现放电模式的转变,这可能有助于对目标回路进行离散作用。

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