No abstract

Olfactory cues are vital for prey animals like rodents to perceive and evade predators. Stress-induced hyperthermia, via brown adipose tissue (BAT) thermogenesis, boosts physical performance and facilitates escape. However, many aspects of this response, including thermogenic control and sex-specific effects, remain enigmatic. Our study unveils that the predator odor trimethylthiazoline (TMT) elicits BAT thermogenesis, suppresses feeding, and drives glucocorticoid release in female mice. Chemogenetic stimulation of olfactory bulb (OB) mitral cells recapitulates the thermogenic output of this response and associated stress hormone corticosterone release in female mice. Neuronal projections from OB to medial amygdala (MeA) and dorsomedial hypothalamus (DMH) exhibit female-specific cFos activity toward odors. Cell sorting and single-cell RNA-sequencing of DMH identify cholecystokinin (CCK)-expressing neurons as recipients of predator odor cues. Chemogenetic manipulation and neuronal silencing of DMHCCK neurons further implicate these neurons in the propagation of predator odor-associated thermogenesis and food intake suppression, highlighting their role in female stress-induced hyperthermia.

Dopaminergic neuron degeneration in the midbrain plays a pivotal role in motor symptoms associated with Parkinson’s disease. However, non-motor symptoms of Parkinson’s disease and post-mortem histopathology confirm dysfunction in other brain areas, including the locus coeruleus and its associated neurotransmitter norepinephrine. Here, we investigate the role of central norepinephrine-producing neurons in Parkinson’s disease by chronically stimulating catecholaminergic neurons in the locus coeruleus using chemogenetic manipulation. We show that norepinephrine neurons send complex axonal projections to the dopaminergic neurons in the substantia nigra, confirming physical communication between these regions. Furthermore, we demonstrate that increased activity of norepinephrine neurons is protective against dopaminergic neuronal depletion in human α-syn A53T missense mutation over-expressing mice and prevents motor dysfunction in these mice. Remarkably, elevated norepinephrine neurons action fails to alleviate α-synuclein aggregation and microgliosis in the substantia nigra suggesting the presence of an alternate neuroprotective mechanism. The beneficial effects of high norepinephrine neuron activity might be attributed to the action of norepinephrine on dopaminergic neurons, as recombinant norepinephrine treatment increased primary dopaminergic neuron cultures survival and neurite sprouting. Collectively, our results suggest a neuroprotective mechanism where noradrenergic neurons activity preserves the integrity of dopaminergic neurons, which prevents synucleinopathy-dependent loss of these cells.

No abstract

When detecting danger signals, animals exhibit adaptive changes in physiology and behavior aimed at increasing survival. In small prey animals, such as rodents, olfactory information plays a fundamental role in the perception of their environment and predator avoidance. Exposure to predation has been associated with reduced fatness in male rodents, but whether similar responses exist in both sexes is poorly understood. Exactly how the nervous system regulates weight in the context of danger perception remains unknown. Here we identify a sex-specific response leading to increased energy expenditure and elevated corticosterone in female mice exposed to predator smell or global stimulation of mitral and tufted cells of the olfactory bulb (OB). This response is absent in male mice and is not attenuated by gonadectomy in females. A population of neurons in the dorsomedial hypothalamus (DMH), selectively activated by aversive olfactory signals also receives polysynaptic afferents from mitral and tufted cells of the main OB (MOB). Cell sorting of projection neurons in the DMH receiving olfactory inputs and single-nucleus RNA-sequencing identify cholecystokinin (Cck)-expressing neurons as putative recipients of olfactory inputs. Chemogenetic stimulation of DMHCCK neurons recapitulates the effects of aversive olfactory stimulation on female energy expenditure. Taken together, our results suggest the existence of a female heightened stress reaction recruiting DMHCCK neurons to promote high energy utilization.