Cellular properties and axonal projections of thyrotropin-releasing hormone-expressing neurons in the mouse lateral...

The lateral hypothalamic area (LHA) is well-known for its conserved role in modulating and driving many forms of innate behaviors, yet the cellular diversity underlying these functions remains incompletely understood. Although neurons expressing the neuropeptide thyrotropin-releasing hormone (TRH) in the hypothalamic paraventricular nucleus have been well-characterized for their hypophysiotropic functions and role in metabolism and feeding behavior, other hypothalamic TRH-expressing neurons, such as those located in the LHA, have received comparatively little attention. Here, using a viral-targeting approach in a Trh-ires-Cre mouse, we probe the anatomical and electrophysiological properties of TRH-expressing neurons in the LHA (LHA^TRH). We find that LHA^TRH neurons make both ascending and descending axonal projections throughout the brain, with particularly dense projections to the regions of the dorsal lateral septum, lateral preoptic, basal forebrain, and dorsal premammillary nuclei. We further define the active and passive membrane properties of LHA^TRH neurons in slices, as well as the morphology of filled neurons. We find that the distinguishing features of LHA^TRH neurons, in contrast to intermingled hypocretin/orexin-expressing neurons, are capable of anode-break bursting in a majority of neurons and exhibit rhythmic spontaneous bursting in a smaller subset of neurons. We further compare the electrophysiological features of both anode-break bursting and nonbursting LHA^TRH neurons, as well as determining that anode-break bursting is mediated by T-type calcium channels. Our work defines both the intrinsic membrane properties, morphology and axonal projections of LHA^TRH neurons, providing a foundation for understanding their roles in physiology and behavior.NEW & NOTEWORTHY This work provides the first characterization of the axonal projections and distinctive electrophysiological properties that define thyrotropin-releasing hormone (TRH)-expressing neurons in the mouse lateral hypothalamic area (LHA) in acute brain slices. We find that a large majority of LHA TRH neurons exhibit robust rebound burst firing, with a smaller subpopulation exhibiting spontaneous rhythmic burst firing. Together, these findings advance our understanding of how LHA TRH neurons may contribute to regulating physiology and behavior.