Histamine Excites Rat GABAergic Ventral Pallidum Neurons via Co-activation of H1 and H2 Receptors

Abstract

The ventral pallidum (VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion. Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamic-derived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.

Impaired Cortical Cytoarchitecture and Reduced Excitability of Deep-Layer Neurons in the Offspring of Diabetic Rats

“…The increase in action potential frequency promoted by histamine in deep-layer cortical neurons is in accordance with the increased excitability previously reported for neurons in other regions of the CNS, namely thalamus (McCormick and Williamson, 1991), layer 6b of the primary somatosensory cortex (Wenger Combremont et al, 2016), entorhinal cortex (Cilz and Lei, 2017), ventral pallidum (Ji et al, 2018), striatum (Zhuang et al, 2018), and spinal cord (Wu et al, 2019). Furthermore, the lack of difference in H 1 R density supports that the electrophysiological changes observed in the offspring of diabetic rats rely mainly on morphological alterations.…”

“…Histamine increases neuronal excitability in several regions of the CNS such as the thalamus ( McCormick and Williamson, 1991 ), layer 6b of the primary somatosensory cortex ( Wenger Combremont et al, 2016 ), entorhinal cortex ( Cilz and Lei, 2017 ), ventral pallidum ( Ji et al, 2018 ), striatum ( Zhuang et al, 2018 ), and spinal cord ( Wu et al, 2019 ). Therefore, we recorded deep layer neurons from P21 pups by injecting depolarizing current in increasing steps under basal and stimulated (1–100 μM histamine) conditions.…”

“…In several brain nuclei histamine increases neuronal excitability through a dual-action mediated by H 1 and H 2 receptors (see for instance McCormick and Williamson, 1991;Ji et al, 2018;Zhuang et al, 2018). The H 1 R-mediated excitatory effect involves a mixed ionic mechanism, namely closing of K + channels, activation of Na + channels and stimulation of the Na + -Ca 2+ exchanger (McCormick and Williamson, 1991;Cilz and Lei, 2017;Wu et al, 2019).…”

Long-Term Functional and Cytoarchitectonic Effects of the Systemic Administration of the Histamine H1 Receptor Antagonist/Inverse Agonist Chlorpheniramine During Gestation in the Rat Offspring Primary Motor Cortex

“…HA increases neuronal excitability through H 1 R activation ( McCormick and Williamson, 1991 ; Ji et al, 2018 ; Zhuang et al, 2018 ). Therefore, H 1 R density was determined in P21 frontal cortex membranes from both groups.…”

Central Histaminergic Signaling, Neural Excitability and Epilepsy

“…Many studies have confirmed that activation of both postsynaptic H1R and H2R co-mediates histamine induced-neuron excitability in several kinds of neurons. For instance, histamine excites dopamine D1 and D2 receptor-expressing striatal GABAergic medium spiny projection neurons, nucleus basalis cholinergic neurons, substantia nigra pars reticulate inhibitory projection neurons, GABAergic ventral pallidum neurons, superior vestibular nuclear neurons, and inferior vestibular nucleus neurons via postsynaptic H1R and H2R (Ji et al, 2018;Khateb, Fort, Pegna, Jones & Mühlethaler, 1995;Peng, Zhuang, He, Zhu & Wang, 2013;Zhou, Xu, Zhao, LeDoux & Zhou, 2006;Zhuang, Wu, Wu, Zhu & Wang, 2013;Zhuang et al, 2018). In medial vestibular nuclear neurons, histamine induces strong postsynaptic excitatory action by Na+-Ca²+ exchangers coupled to H1R and HCN linked to H2R (Zhang, Yu, Zhuang, Peng, Zhu & Wang, 2013).…”