Selective serotonergic excitation of callosal projection neurons.
Selective serotonergic excitation of callosal projection neurons.
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DOI：
10.3389/fncir.2012.00012
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发表时间：
2012
影响因子：
3.5
通讯作者：
Gulledge AT
中科院分区：
文献类型：
--
作者：
Avesar D;Gulledge AT
血清素 (5-HT) 作为大脑皮层中的神经递质，对于认知功能至关重要，但 5-HT 如何调节皮层回路中的信息处理尚不清楚。我们测试了小鼠内侧前额叶皮层 (mPFC) 中第 5 层锥体神经元 (L5PN) 的血清素反应性，发现了三种不同的反应类型：持久的 5-HT1A (1A) 受体依赖性抑制反应（L5PN 的 84%）、5-HT2A (2A) 受体依赖性兴奋性反应 (9%) 以及 2A 依赖性兴奋随后短暂抑制的双相反应(5%)。相对于 5-HT 抑制的神经元，那些被 5-HT 兴奋的神经元具有投射到对侧皮层的胼胝体/连合 (COM) 神经元的生理特性。我们使用 COM 和皮质桥脑投射 (CPn) 神经元的逆行荧光标记来测试皮质锥体神经元中的血清素反应是否与其轴突投射模式相关。 5-HT 在所有 5-HT 反应第 5 层 COM 神经元中产生兴奋性或双相反应。相反，CPn 神经元普遍被 5-HT 抑制。 COM 神经元的血清素能兴奋被 2A 拮抗剂 MDL 11939 阻断，而 CPn 神经元的血清素能抑制被 1A 拮抗剂 WAY 100635 阻断，证实了这两种受体亚型在调节锥体神经元活动中的作用。 COM 神经元的选择性血清素兴奋不是层特异性的，因为相对于其未标记的锥体神经元邻居，2/3 层中的 COM 神经元也被 5-HT 选择性兴奋。由于新皮质 2A 受体与精神分裂症的病因学和病理生理学有关，因此我们认为 COM 神经元可能代表精神疾病干预的新细胞靶点。
Serotonin (5-HT) acting as a neurotransmitter in the cerebral cortex is critical for cognitive function, yet how 5-HT regulates information processing in cortical circuits is not well understood. We tested the serotonergic responsiveness of layer 5 pyramidal neurons (L5PNs) in the mouse medial prefrontal cortex (mPFC), and found three distinct response types: long-lasting 5-HT1A (1A) receptor-dependent inhibitory responses (84% of L5PNs), 5-HT2A (2A) receptor-dependent excitatory responses (9%), and biphasic responses in which 2A-dependent excitation followed brief inhibition (5%). Relative to 5-HT-inhibited neurons, those excited by 5-HT had physiological properties characteristic of callosal/commissural (COM) neurons that project to the contralateral cortex. We tested whether serotonergic responses in cortical pyramidal neurons are correlated with their axonal projection pattern using retrograde fluorescent labeling of COM and corticopontine-projecting (CPn) neurons. 5-HT generated excitatory or biphasic responses in all 5-HT-responsive layer 5 COM neurons. Conversely, CPn neurons were universally inhibited by 5-HT. Serotonergic excitation of COM neurons was blocked by the 2A antagonist MDL 11939, while serotonergic inhibition of CPn neurons was blocked by the 1A antagonist WAY 100635, confirming a role for these two receptor subtypes in regulating pyramidal neuron activity. Selective serotonergic excitation of COM neurons was not layer-specific, as COM neurons in layer 2/3 were also selectively excited by 5-HT relative to their non-labeled pyramidal neuron neighbors. Because neocortical 2A receptors are implicated in the etiology and pathophysiology of schizophrenia, we propose that COM neurons may represent a novel cellular target for intervention in psychiatric disease.
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