建立功能分离的多巴胺突触的投影特异信号
Akiko Terauchi1, Patricia Yee1, Erin M Johnson-Venkatesh1
1Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell
|August 17, 2023
概括
两个TGF-β家族成员,BMPs和TGF-β2,控制着不同的大脑路径. 这些因子通过Smad蛋白质指导阴静脉 (运动) 和半边缘 (动机) 胺突触的发育.
科学领域:
- 神经科学
- 分子生物学
- 发育生物学
背景情况:
- 多巴胺能预测对大脑功能至关重要,并与神经精神疾病有关.
- 截然不同的内 (运动) 和中 (动机) 途径起源于中脑.
- 建立这些特定多巴胺突触连接的机制尚不清楚.
研究的目的:
- 确定不同多巴胺突触发育的分子调节剂.
- 阐明TGF-β家族成员在内和中路中的作用.
- 了解投射特异性突触形成中的下游信号通路.
主要方法:
- 没有偏见的基因查以确定调节因素.
- 对多巴胺基神经元的受体表达模式的分析.
- 通过Smad蛋白来研究下游的信号通路.
- 使用突变小鼠模型来评估功能后果.
主要成果:
- 骨形态蛋白 (BMP) 6/ BMP2 和转化生长因子 (TGF) -β2 分别调节中和中皮多巴胺突触的发育.
- 投射偏好的受体表达对于特定的突触形成至关重要.
- Smad1和Smad2是特别激活的,并且对于独特的多巴胺突出的发展和功能是必需的.
- 缺少Smad1会导致运动缺陷,而缺少Smad2会导致动机障碍.
结论:
- 确定了BMP和TGF-β2作为功能分离的多巴胺突触发育的关键调节剂.
- 揭示了Smad1和Smad2在预测特异性多巴胺功能的不同作用.
- 这些发现为多巴胺系统组织的分子逻辑提供了洞察力.
- 建议针对特异性神经和精神疾病的特异性TGF-β信号组件进行潜在的治疗策略.
相关概念视频
01:09Synaptic Signaling
5.6K
Neurons communicate at synapses, or junctions, to excite or inhibit the activity of other neurons or target cells, such as muscles. Synapses may be chemical or electrical.
Most synapses are chemical, meaning an electrical impulse or action potential spurs the release of chemical messengers called neurotransmitters. The neuron sending the signal is called the presynaptic neuron, and the neuron receiving the signal is the postsynaptic neuron.
The presynaptic neuron fires an action potential that...
Most synapses are chemical, meaning an electrical impulse or action potential spurs the release of chemical messengers called neurotransmitters. The neuron sending the signal is called the presynaptic neuron, and the neuron receiving the signal is the postsynaptic neuron.
The presynaptic neuron fires an action potential that...
5.6K
02:47The Synapse
125.6K
Neurons communicate with one another by passing on their electrical signals to other neurons. A synapse is the location where two neurons meet to exchange signals. At the synapse, the neuron that sends the signal is called the presynaptic cell, while the neuron that receives the message is called the postsynaptic cell. Note that most neurons can be both presynaptic and postsynaptic, as they both transmit and receive information.
125.6K
01:26Chemical Synapses
8.9K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
8.9K