Electrophysiological Properties of Genetically Identified Histaminergic Neurons

Abstract

Histaminergic neurons of the tuberomammillary nucleus (TMN) are important regulators of behavioral and homeostatic processes. Previous work suggested that histaminergic neurons exhibit a characteristic electrophysiological signature, allowing for their identification in brain slice preparations. However, these previous investigations focused on neurons in the ventral subregion of the TMN of rats. Consequently, it remains unclear whether such electrophysiological properties extend to mice, including other subregions of the TMN, and the potential for differences between males and females. To further characterize the electrophysiological properties of histaminergic neurons, we performed whole-cell patch-clamp recordings on transgenic mice expressing Cre recombinase in histidine decarboxylase (HDC)-expressing cells; the sole enzyme for histamine synthesis (Hdc-cre::tdTomato). Despite similarities with the electrophysiological properties reported in rats, we observed considerable variability in mouse HDC neuron passive membrane properties, action potential firing, and intrinsic subthreshold active membrane properties. Overall, the electrophysiological properties of HDC neurons appeared similar across subregions of the TMN, consistent with a lack of topographical organization in this nucleus. Moreover, we found no obvious sex differences in the electrical excitability of HDC neurons. However, our data reveal a diversity in the electrophysiological properties of genetically identified histaminergic neurons from mice not previously appreciated from rat studies. Thus, these data highlight the utility of mouse genetics to target the widespread histaminergic neuronal population within the TMN and support the idea that histaminergic neurons are a heterogeneous neuronal population.

Keywords: electrophysiology; histaminergic neurons; hypothalamus; sex differences; tuberomammillary nucleus.