Pre-locus coeruleus neurons in rat and mouse.

Abstract

Previously, we identified a population of neurons in the hindbrain tegmentum, bordering the locus coeruleus (LC). We named this population the pre-locus coeruleus (pre-LC) because in rats its neurons lie immediately rostral to the LC. In mice, however, pre-LC and LC neurons intermingle, making them difficult to distinguish. Here, we use molecular markers and anterograde tracing to clarify the location and distribution of pre-LC neurons in mice, relative to rats. First, we colocalized the transcription factor FoxP2 with the activity marker Fos to identify pre-LC neurons in sodium-deprived rats and show their distribution relative to surrounding catecholaminergic and cholinergic neurons. Next, we used sodium depletion and chemogenetic activation of the aldosterone-sensitive HSD2 neurons in the nucleus of the solitary tract (NTS) to identify the homologous population of pre-LC neurons in mice, along with a related population in the central lateral parabrachial nucleus. Using Cre-reporter mice for Pdyn, we confirmed that most of these sodium-depletion-activated neurons are dynorphinergic. Finally, after confirming that these neurons receive excitatory input from the NTS and paraventricular hypothalamic nucleus, plus convergent input from the inhibitory AgRP neurons in the arcuate hypothalamic nucleus, we identify a major, direct input projection from the medial prefrontal cortex. This new information on the location, distribution, and input to pre-LC neurons provides a neuroanatomical foundation for cell-type-specific investigation of their properties and functions in mice. Pre-LC neurons likely integrate homeostatic information from the brainstem and hypothalamus with limbic, contextual information from the cerebral cortex to influence ingestive behavior.