Neuroanatomical connections between the TMN and NTS confirmed by a retrograde tracer, Fluoro‐Gold. Fluoro‐Gold microinjected in the NTS was found in specific areas of the TMN in the posterior hypothalamic region (A, bregma −3.8 mm; B, bregma −4.2 mm; C, a magnified image of the dotted square in [A]; D, a magnified image of the dotted square in [B]) demonstrating a direct projection from the ventral TMN to the NTS. These areas in the TMN are known to contain histidine decarboxylase (HDC)‐positive neurons (E2 and E3, i.e., histaminergic neurons, see text). V3, third ventricle; LH, lateral hypothalamus; VMH, ventromedial hypothalamus; vTMN, ventral tuberomammillary nucleus.
A schematic illustration of the presumptive pathway between TMN histamine projections to NTS and its effects on cardiovascular regulation. Microinjection of histamine H1 receptor antagonist partially prevented the pressor effect but had no effect on heart rate in response to electrical stimulation of the ventral TMN (Fig. 2). This is because ventral TMN neurons mainly modulate NTS neurons that control “vasomotor” sympathetic outflow. Electrical stimulation of the ventral TMN evokes histamine release from synaptic terminals and activates NTS neurons with histamine receptors that receive ventral TMN inputs. In addition, electrical stimulation of the ventral TMN not only directly activates the NTS projection pathway but also indirectly and/or independently activates through the other brain areas that control both “vasomotor” sympathetic and “cardiac” sympathetic and/or parasympathetic nerve activities. NTS, nucleus tractus solitarius; TMN, tuberomammillary nucleus.
Cardiovascular changes induced by bicuculline, a GABAA receptor antagonist, microinjected into the ventral part of the TMN. Representative recordings illustrating the cardiovascular changes induced by bicuculline (BIC, 1, 10, and 100 pmol/50 nL) unilaterally microinjected into the ventral TMN (A). Bicuculline microinjection elicited increases in pulsatile AP, MAP, and HR. Group data show the dose‐dependent increase in both MAP (B, top) and HR (B, bottom) in response to bicuculline microinjection (1 pmol: n = 5; 10 pmol: n = 5; 100 pmol: n = 7). Saline was used as a control (n = 4). *P < 0.05, **P < 0.01. TMN, tuberomammillary nucleus; AP, arterial pressure; MAP, mean arterial pressure; HR, heart rate.
Cardiovascular changes elicited by electrical stimulation of the ventral TMN and inhibitory effects of cetirizine (H1 receptor‐specific antagonist) microinjected into the NTS. The ventral TMN was electrically stimulated by a microelectrode in anesthetized rats. Similar to the cardiovascular responses evoked by bicuculline microinjections into the VTM (see Fig. 1), pressor and tachycardic responses were observed (A, left). The pressor responses were partially inhibited by cetirizine (100 pmol/50 nL) microinjected into the NTS (A, right). Group data show the inhibitory effects of cetirizine on TMN stimulation‐induced pressor response but not in the tachycardic response (B). The lesion of the ventral TMN shows where the microelectrode was located (C). V3, third ventricle. TMNs, TMN stimulation. NTSa, NTS antagonist injection
c‐Fos expression in the TMN and NTS after treadmill running test. c‐Fos‐positive cells were identified in the ventral TMN (A) and the NTS (B) after physical activity on the treadmill running test (arrowhead in right panels). The c‐Fos immunoreactivity in the TMN and NTS was much less in the no‐exercise group (C TMN; D, NTS), suggesting that these nuclei are activated by a single bout of exercise. V3, third ventricle; cc, central canal; vTMN, ventral tuberomammillary nucleus; NTS, nucleus tractus solitarius.