A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Somatosensory cortex and central amygdala regulate neuropathic pain-mediated peripheral immune response via vagal projections to the spleen.

Pain involves neuroimmune crosstalk, but the mechanisms of this remain unclear. Here we showed that the splenic T helper 2 (TH2) immune cell response is differentially regulated in male mice with acute versus chronic neuropathic pain and that acetylcholinergic neurons in the dorsal motor nucleus of the vagus (AChDMV) directly innervate the spleen. Combined in vivo recording and immune cell profiling revealed the following two distinct circuits involved in pain-mediated peripheral TH2 immune response: glutamatergic neurons in the primary somatosensory cortex (GluS1HL)→AChDMV→spleen circuit and GABAergic neurons in the central nucleus of the amygdala (GABACeA)→AChDMV→spleen circuit. The acute pain condition elicits increased excitation from GluS1HL neurons to spleen-projecting AChDMV neurons and increased the proportion of splenic TH2 immune cells. The chronic pain condition increased inhibition from GABACeA neurons to spleen-projecting AChDMV neurons and decreased splenic TH2 immune cells. Our study thus demonstrates how the brain encodes pain-state-specific immune responses in the spleen.

Brain regulation of gastric dysfunction induced by stress.

Psychological and physical stressors have been implicated in gastric disorders in humans. The mechanism coupling the brain to the stomach underlying stress-induced gastric dysfunction has remained elusive. Here, we show that the stomach directly receives acetylcholinergic inputs from the dorsal motor nucleus of the vagus (AChDMV), which are innervated by serotonergic neurons in the dorsal raphe nucleus (5-HTDRN). Microendoscopic calcium imaging and multi-tetrode electrophysiological recordings reveal that the 5-HTDRN → AChDMV → stomach circuit is inhibited with chronic stress accompanied by hypoactivate gastric function. Artificial activation of this circuit reverses the gastric dysfunction induced by chronic stress in both male and female mice. Our study demonstrates that this 5-HTDRN → AChDMV → stomach axis drives gastric dysfunction associated with stress, thus providing insights into the circuit basis for brain regulation of the stomach.

Green light induces antinociception via visual-somatosensory circuits.

Light has been shown to relieve pain, but the underlying neural mechanisms remain unknown. Here, we show that low-intensity (200 lux) green light treatment exerts antinociceptive effects through a neural circuit from the visual cortex projecting to the anterior cingulate cortex (ACC) in mice. Specifically, viral tracing, in vivo two-photon calcium imaging, and fiber photometry recordings show that green light activated glutamatergic projections from the medial part of the secondary visual cortex (V2MGlu) to GABAergic neurons in the ACC, which drives inhibition of local glutamatergic neurons (V2MGlu→ACCGABA→Glu). Optogenetic or chemogenetic activation of the V2MGlu→ACCGABA→Glu circuit mimics green-light-induced antinociception in both neuropathic and inflammatory pain model mice. Artificial inhibition of ACC-projecting V2MGlu neurons abolishes the antinociception induced by green light. Taken together, our study shows the V2M-ACC circuit as a potential candidate mediating green-light-induced antinociceptive effects.

A neural circuit for the suppression of feeding under persistent pain.

In humans, persistent pain often leads to decreased appetite. However, the neural circuits underlying this behaviour remain unclear. Here, we show that a circuit arising from glutamatergic neurons in the anterior cingulate cortex (GluACC) projects to glutamatergic neurons in the lateral hypothalamic area (GluLHA) to blunt food intake in a mouse model of persistent pain. In turn, these GluLHA neurons project to pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus (POMCArc), a well-known neuronal population involved in decreasing food intake. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that the GluACC → GluLHA → Arc circuit is activated in mouse models of persistent pain and is accompanied by decreased feeding behaviour in both males and females. Inhibition of this circuit using chemogenetics can alleviate the feeding suppression symptoms. Our study indicates that the GluACC → GluLHA → Arc circuit is involved in driving the suppression of feeding under persistent pain through POMC neuronal activity. This previously unrecognized pathway could be explored as a potential target for pain-associated diseases.

Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states.

In humans, tissue injury and depression can both cause pain hypersensitivity, but whether this involves distinct circuits remains unknown. Here, we identify two discrete glutamatergic neuronal circuits in male mice: a projection from the posterior thalamic nucleus (POGlu) to primary somatosensory cortex glutamatergic neurons (S1Glu) mediates allodynia from tissue injury, whereas a pathway from the parafascicular thalamic nucleus (PFGlu) to anterior cingulate cortex GABA-containing neurons to glutamatergic neurons (ACCGABA→Glu) mediates allodynia associated with a depression-like state. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that POGlu and PFGlu populations undergo different adaptations in the two conditions. Artificial manipulation of each circuit affects allodynia resulting from either tissue injury or depression-like states, but not both. Our study demonstrates that the distinct thalamocortical circuits POGlu→S1Glu and PFGlu→ACCGABA→Glu subserve allodynia associated with tissue injury and depression-like states, respectively, thus providing insights into the circuit basis of pathological pain resulting from different etiologies.

Morphological and Ultrastructural Characterization of Antennal Sensilla and the Detection of Floral Scent Volatiles in Eupeodes corollae (Diptera: Syrphidae).

The olfactory sensing system of the syrphid fly Eupeodes corollae is essential in pollination and prey localization, but little is known about the ultrastructural organization of their olfactory organs. In this study, the morphology, distribution, and ultrastructural organization of antennal sensilla of E. corollae in both sexes were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Neuronal responses of a subtype of sensilla basiconica to floral scent compounds were recorded by single sensillum recording (SSR). Ten morphological types, including Böhm bristles, sensilla chaetica, microtrichiae, sensilla trichodea, sensilla basiconica, sensilla clavate, sensilla coeloconica, sensilla styloconica, sensilla placodea, and sensory pit, were identified. Except for Böhm bristles and sensilla chaetica, which were distributed on the scape and pedicel of E. corollae antennae, innervated sensilla were densely distributed on the flagellum, a vital sensory organ. Further, observing ultrastructural organization showed that the sensilla trichodea, basiconica, and clavate are single-walled with multiple nanoscale pores perforating the cuticle. Sensilla coeloconica are double-walled and have no wall pores, but instead, have longitudinal grooves along with the pegs. Sensilla chaetica, Böhm bristles, and microtrichiae did not have wall pores on the cuticle or sensory cells at the base. The SSR results indicated that neuron B housed in the subtype of sensilla basiconica I (SBI) mainly responded to methyl eugenol and other aromatic compounds. Overall, our results provide valuable information to understand the morphology and ultrastructure of antennal sensilla from E. corollae. These findings are beneficial for the studies of the neuronal function map of olfactory sensilla and for determining evolutionary relationships in Diptera.

Sox genes in Agasicles hygrophila (Coleoptera: Chrysomelidae) are involved in ovarian development and oogenesis.

The alligator weed flea beetle, Agasicles hygrophila is a monophagous natural enemy of the invasive alligator weed Alternanthera philoxeroides. Oogenesis plays a vital role in the process of individual development and population continuation of oviparous insects. Sox is an ancient and ubiquitous metazoan gene family that plays a key regulatory role in various physiological processes, including oogenesis, which is closely related to fecundity. In this study, two Sox genes AhDichaete and AhSox3 were cloned and characterized, and then the expression profiles of AhDichaete and AhSox3 were qualified by a quantitative reverse transcription-polymerase chain reaction. The result showed that these two Sox genes were expressed significantly higher in ovary, especially in the adult developmental stage. Furthermore, the functions of AhDichaete and AhSox3 in A. hygrophila females were studied using RNA interference (RNAi). Fewer offsprings were produced when AhDichaete and AhSox3 RNAi females mated with wild-type males. Moreover, dsAhSox3 injection reduced the hatching rate of eggs but injection with dsAhDichaete did not. Further study of the reproductive system of AhDichaete and AhSox3 RNAi females showed that yolk protein deposition reduction in the ovarioles, then the expression of vitellogenin gene AhVg2 in ovaries was decreased. These results indicate that AhDichaete and AhSox3 play an important regulatory role in the process of ovarian development and oogenesis by affecting yolk synthesis in the ovary of A. hygrophila.