Lee Kendall H, Broberger Christian, Kim Uhnoh, McCormick David A
Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6716-21. doi: 10.1073/pnas.0400817101. Epub 2004 Apr 19.
In the mammalian central nervous system only gamma-aminobutyric acid (GABA) and glycine have been firmly linked to inhibition of neuronal activity through increases in membrane Cl(-) conductance, and these responses are mediated by ionotropic receptors. Iontophoretic application of histamine can also cause inhibitory responses in vivo, although the mechanisms of this inhibition are unknown and may involve pre- or postsynaptic factors. Here, we report that application of histamine to the GABAergic neurons of the thalamic perigeniculate nucleus (PGN), which is innervated by histaminergic fibers from the tuberomammillary nucleus of the hypothalamus, causes a slow membrane hyperpolarization toward a reversal potential of -73 mV through a relatively small increase in membrane conductance to Cl(-). This histaminergic action appears to be mediated by the H(2) subclass of histaminergic receptors and inhibits the single-spike activity of these PGN GABAergic neurons. Application of histamine to the PGN could halt the generation of spindle waves, indicating that increased activity in the tuberomammillary histaminergic system may play a functional role in dampening thalamic oscillations in the transition from sleep to arousal.
在哺乳动物中枢神经系统中，只有γ-氨基丁酸（GABA）和甘氨酸通过增加膜对Cl⁻的电导与抑制神经元活动紧密相关，并且这些反应由离子型受体介导。组胺的离子电渗应用在体内也可引起抑制反应，尽管这种抑制的机制尚不清楚，可能涉及突触前或突触后因素。在这里，我们报告，将组胺应用于丘脑膝状周核（PGN）的GABA能神经元，该神经元受来自下丘脑结节乳头核的组胺能纤维支配，通过相对较小地增加膜对Cl⁻的电导，使膜缓慢超极化至反转电位-73 mV。这种组胺能作用似乎由组胺能受体的H₂亚类介导，并抑制这些PGN GABA能神经元的单峰活动。将组胺应用于PGN可阻止纺锤波的产生，表明结节乳头组胺能系统活动增加可能在从睡眠到觉醒的转变中抑制丘脑振荡中发挥功能性作用。
