GLP-1 neurons form a local synaptic circuit within the rodent nucleus of the solitary tract.
GLP-1 neurons form a local synaptic circuit within the rodent nucleus of the solitary tract.
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DOI：
10.1002/cne.24482
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发表时间：
2018-10-01
期刊：
影响因子：
--
通讯作者：
Rinaman L
中科院分区：
文献类型：
--
作者：
Card JP;Johnson AL;Llewellyn-Smith IJ;Zheng H;Anand R;Brierley DI;Trapp S;Rinaman L
表达前胰高血糖素原（PPG）且胰高血糖素样肽-1免疫阳性（+）的谷氨酸能神经元（即，GLP-1+神经元）位于大鼠和小鼠孤束尾核（cNTS）和延髓网状结构内。GLP-1神经元产生广泛的中枢网络，其中GLP-1受体（GLP-1 R）信号传导抑制食物摄入，减弱奖励，增加回避，并刺激应激反应，部分通过cNTS内的GLP-1 R信号传导。在小鼠中，去甲肾上腺素能（A2）cNTS神经元表达GLP-1 R，而PPG神经元不表达。在这项研究中，大鼠共聚焦显微镜证实，催乳素释放肽（PrRP）+ A2神经元与GLP-1+轴突静脉曲张紧密贴壁。令人惊讶的是，在两个物种的PPG/GLP-1+神经元的树突上也观察到GLP-1+沉积，大鼠的电子显微镜显示GLP-1+终扣与GLP-1+树突形成不对称的突触接触。然而，RNAscope证实大鼠GLP-1神经元不表达GLP-1 R mRNA。同样，小鼠离体切片中体细胞和树突反应的Ca 2+成像证实PPG神经元不直接对GLP-1产生反应，小鼠杂交育种策略显示<1%的PPG神经元共表达GLP-1 R。总的来说，这些数据表明GLP-1 R信号通路调节PrRP+ A2神经元的活性，并且还揭示了GLP-1神经元之间的局部“前馈”突触网络，其显然不使用GLP-1 R信号。这种局部GLP-1网络可能会使用神经元能信号来促进GLP-1神经群体的动态和潜在选择性募集，这些神经群体塑造了对内部和外部挑战的行为和生理反应。
Glutamatergic neurons that express pre‐proglucagon (PPG) and are immunopositive (+) for glucagon‐like peptide‐1 (i.e., GLP‐1+ neurons) are located within the caudal nucleus of the solitary tract (cNTS) and medullary reticular formation in rats and mice. GLP‐1 neurons give rise to an extensive central network in which GLP‐1 receptor (GLP‐1R) signaling suppresses food intake, attenuates rewarding, increases avoidance, and stimulates stress responses, partly via GLP‐1R signaling within the cNTS. In mice, noradrenergic (A2) cNTS neurons express GLP‐1R, whereas PPG neurons do not. In this study, confocal microscopy in rats confirmed that prolactin‐releasing peptide (PrRP)+ A2 neurons are closely apposed by GLP‐1+ axonal varicosities. Surprisingly, GLP‐1+ appositions were also observed on dendrites of PPG/GLP‐1+ neurons in both species, and electron microscopy in rats revealed that GLP‐1+ boutons form asymmetric synaptic contacts with GLP‐1+ dendrites. However, RNAscope confirmed that rat GLP‐1 neurons do not express GLP‐1R mRNA. Similarly, Ca2+ imaging of somatic and dendritic responses in mouse ex vivo slices confirmed that PPG neurons do not respond directly to GLP‐1, and a mouse crossbreeding strategy revealed that <1% of PPG neurons co‐express GLP‐1R. Collectively, these data suggest that GLP‐1R signaling pathways modulate the activity of PrRP+ A2 neurons, and also reveal a local “feed‐forward” synaptic network among GLP‐1 neurons that apparently does not use GLP‐1R signaling. This local GLP‐1 network may instead use glutamatergic signaling to facilitate dynamic and potentially selective recruitment of GLP‐1 neural populations that shape behavioral and physiological responses to internal and external challenges.
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影响因子：
8.1
作者：
Holt MK;Llewellyn-Smith IJ;Reimann F;Gribble FM;Trapp S
通讯作者：
Trapp S
DOI：
10.1523/jneurosci.3262-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dossat AM;Lilly N;Kay K;Williams DL
通讯作者：
Williams DL
影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Gnanamanickam, G. J. E.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
影响因子：
3.3
作者：
Larsen, PJ;TangChristensen, M;Orskov, C
通讯作者：
Orskov, C