Histamine Excites Rat Superior Vestibular Nuclear Neurons via Postsynaptic H1 and H2 Receptors in vitro

Abstract

The superior vestibular nucleus (SVN), which holds a key position in vestibulo-ocular reflexes and nystagmus, receives direct hypothalamic histaminergic innervations. By using rat brainstem slice preparations and extracellular unitary recordings, we investigated the effect of histamine on SVN neurons and the underlying receptor mechanisms. Bath application of histamine evoked an excitatory response of the SVN neurons, which was not blocked by the low-Ca²⁺/high-Mg²⁺ medium, indicating a direct postsynaptic effect of the amine. Selective histamine H₁ receptor agonist 2-pyridylethylamine and H₂ receptor agonist dimaprit, rather than VUF8430, a selective H₄ receptor agonist, mimicked the excitation of histamine on SVN neurons. In addition, selective H₁ receptor antagonist mepyramine and H₂ receptor antagonist ranitidine, but not JNJ7777120, a selective H₄ receptor antagonist, partially blocked the excitatory response of SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly totally blocked the histamine-induced excitation. Immunostainings further showed that histamine H₁ and H₂ instead of H₄ receptors existed in the SVN. These results demonstrate that histamine excites the SVN neurons via postsynaptic histamine H₁ and H₂ receptors, and suggest that the central histaminergic innervation from the hypothalamus may actively bias the SVN neuronal activity and subsequently modulate the SVN-mediated vestibular functions and gaze control.