Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex:: Involvement of serotonin-1A, GABAA, and glutamate receptors
Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex:: Involvement of serotonin-1A, GABAA, and glutamate receptors
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DOI：
10.1523/jneurosci.21-24-09917.2001
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发表时间：
2001-12-15
影响因子：
5.3
通讯作者：
Artigas, F
中科院分区：
文献类型：
--
作者：
Celada, P;Puig, MV;Artigas, F
解剖学证据表明，内侧前额叶皮质（mPFC）神经元投射到中缝背核（DR）。在这项研究中，我们的功能特点是这种下行通路在大鼠大脑。在mPFC中的投射神经元被确定为从DR的逆行刺激。电刺激mPFC主要抑制DR 5-HT神经元的活动（55/66）。刺激周时间直方图显示刺激后150 +/- 9毫秒的沉默（潜伏期，36 +/- 1毫秒）。给予WAY-100635和苦毒宁部分逆转了这种抑制作用，表明5-HT 1A和GABA（A）受体参与。对氯苯丙氨酸耗竭5-HT的大鼠，电刺激mPFC主要激活5-HT神经元（31/40）。兴奋（潜伏期，17 +/- 1毫秒）被MK-801和NBQX拮抗。同样，MK-801阻止了电刺激mPFC诱导的DR 5-HT释放的增加。在mPFC中应用8-OH-DPAT显著抑制DR 5-HT神经元的放电率，并且在双探针微透析实验中，减少了mPFC和DR中的5-HT输出。此外，在mPFC中应用WAY-100635显著拮抗全身8-OH-DPAT给药在两个区域产生的5-HT释放的减少。这些结果表明，存在一个复杂的调节DR 5-HT神经元的mPFC传入。下行兴奋性纤维对某些5-HT神经元的刺激诱导的兴奋释放5-HT，其通过作用于5-HT 1A自身受体来抑制相同或其他DR神经元。来自mPFC的传入还通过激活GABA能中间神经元来抑制5-HT神经元。肾上腺素能上行通路可能通过作用于突触后5-HT 1A受体来控制该下行通路的活性。
Anatomical evidence indicates that medial prefrontal cortex (mPFC) neurons project to the dorsal raphe nucleus (DR). In this study, we functionally characterized this descending pathway in rat brain. Projection neurons in the mPFC were identified by antidromic stimulation from the DR. Electrical stimulation of the mPFC mainly inhibited the activity of DR 5-HT neurons (55 of 66). Peristimulus time histograms showed a silence of 150 +/- 9 msec poststimulus (latency, 36 +/- 1 msec). The administration of WAY-100635 and picrotoxinin partly reversed this inhibition, indicating the involvement of 5-HT1A and GABA(A) receptors. In rats depleted of 5-HT with p-chlorophenylalanine, the electrical stimulation of mPFC mainly activated 5-HT neurons (31 of 40). The excitations (latency, 17 +/- 1 msec) were antagonized by MK-801 and NBQX. Likewise, MK-801 prevented the rise in DR 5-HT release induced by electrical stimulation of mPFC. The application of 8-OH-DPAT in mPFC significantly inhibited the firing rate of DR 5-HT neurons and, in dual-probe microdialysis experiments, reduced the 5-HT output in mPFC and DR. Furthermore, the application of WAY-100635 in mPFC significantly antagonized the reduction of 5-HT release produced by systemic 8-OH-DPAT administration in both areas. These results indicate the existence of a complex regulation of DR 5-HT neurons by mPFC afferents. The stimulus-induced excitation of some 5-HT neurons by descending excitatory fibers releases 5-HT, which inhibits the same or other DR neurons by acting on 5-HT1A autoreceptors. Afferents from the mPFC also inhibit 5-HT neurons through the activation of GABAergic interneurons. Ascending serotonergic pathways may control the activity of this descending pathway by acting on postsynaptic 5-HT1A receptors.