Lee Karen K Y, Soutar Chloe N, Dringenberg Hans C
Department of Psychology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
Brain Res. 2018 Mar 15;1683:1-11. doi: 10.1016/j.brainres.2018.01.004. Epub 2018 Jan 8.
The neuromodulator serotonin (5-hydroxytryptamine, 5-HT) plays an important role in controlling the induction threshold and maintenance of long-term potentiation (LTP) in the visual cortex and hippocampus of rodents. Serotonergic fibers also innervate the rodent primary auditory cortex (A1), but the regulation of A1 plasticity by 5-HT receptors (5-HTRs) is largely uncharted. Thus, we examined the role of several, predominant 5-HT receptor classes (5-HTRs, 5-HTRs, and 5-HTRs) in gating in vivo LTP induction at A1 synapses of adult, urethane-anesthetized rats. Theta-burst stimulation (TBS) applied to the medial geniculate nucleus resulted in successful LTP induction of field postsynaptic potentials (fPSPs) generated by excitation of thalamocortical and intracortical A1 synapses. Local application (by reverse microdialysis in A1) of the broad-acting 5-HTR antagonist methiothepin suppressed LTP at both thalamocortical and intracortical synapses. In fact, rather than LTP, TBS elicited long-term depression during methiothepin application, an effect that was mimicked by the selective 5-HTR antagonist ketanserin, but not the 5-HTR blocker WAY 100635. Interestingly, antagonism of 5-HTRs by granisetron selectively blocked LTP at thalamocortical, but not intracortical A1 synapses. Further, in the absence of TBS, granisetron application resulted in a pronounced increase in fPSP amplitude, suggesting that 5-HTRs play an important role in regulating baseline (non-potentiated) transmission at A1 synapses. Together, these results indicate that activation of 5-HTRs and 5-HTRs, but not 5-HTRs, exerts a clear, facilitating effect on LTP induction at A1 synapses, allowing 5-HT to act as a powerful regulator of long-term plasticity induction in the fully matured A1 of mammalian species.
神经调质血清素（5-羟色胺，5-HT）在控制啮齿动物视觉皮层和海马体中长时程增强（LTP）的诱导阈值和维持方面发挥着重要作用。血清素能纤维也支配啮齿动物的初级听觉皮层（A1），但5-羟色胺受体（5-HTRs）对A1可塑性的调节在很大程度上尚不清楚。因此，我们研究了几种主要的5-羟色胺受体类型（5-HTR1s、5-HTR2s和5-HTR7s）在成年、氨基甲酸乙酯麻醉大鼠A1突触体内LTP诱导门控中的作用。施加于内侧膝状体的theta爆发刺激（TBS）成功诱导了丘脑皮质和皮质内A1突触兴奋产生的场突触后电位（fPSP）的LTP。广泛作用的5-HTR拮抗剂美替拉酮通过在A1中反向微透析进行局部应用，抑制了丘脑皮质和皮质内突触的LTP。事实上，在应用美替拉酮期间，TBS引发的不是LTP，而是长时程抑制，选择性5-HTR拮抗剂酮色林可模拟这种效应，但5-HTR阻滞剂WAY 100635则不能。有趣的是，格拉司琼对5-HTR7s的拮抗作用选择性地阻断了丘脑皮质A1突触的LTP，但未阻断皮质内A1突触的LTP。此外，在没有TBS的情况下，应用格拉司琼导致fPSP幅度显著增加，表明5-HTR7s在调节A1突触的基线（非增强）传递中起重要作用。总之，这些结果表明，5-HTR1s和5-HTR2s的激活而非5-HTR7s的激活，对A1突触的LTP诱导具有明显的促进作用，使5-HT能够作为哺乳动物物种完全成熟的A1中长时可塑性诱导的强大调节剂。
