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Trevizan-Bau, P.

Publications and source records attributed to Trevizan-Bau, P..

3 recordsLinked to original sources

Immune responses to infection modulate peripheral sympathetic neuron functions

The central nervous system interprets inflammatory signals in the body and directs the modulation of inflammatory responses by reflexively engaging peripheral sympathetic neurons1,2. This includes sympathetic neurons that innervate the spleen, which can regulate immune functions3-5 and modulate inflammation6-8. Yet, it is unclear if neuroimmune interactions involve specialised immunoregulatory sympathetic neurons, and if the immune system can reciprocally regulate peripheral sympathetic neurons to control these responses. Using retrograde tracing and single-cell transcriptomics, we find that spleen-innervating neurons are heterogeneous but do not exhibit a distinct transcriptional program indicative of specialisation for immune communication. However, we report that immune responses induced by pathogens can regulate postganglionic sympathetic neuron functions. Cytokines produced by immune cells downregulate expression of the neurotrophin nerve growth factor in spleen mesenchymal cells, leading to organ-specific sympathetic nerve retraction from the spleen. Concurrently, splenic type I interferon signalling induces inflammatory gene expression in neurons and suppresses neuron excitability. Chemogenetic activation of sympathetic neurons demonstrates an impaired anti-inflammatory capacity in the spleen during infection. These results reveal regulation of sympathetic neuronal functions by the immune system, which could support optimal generation of immune responses against pathogens.

immunology↗

Brain-body circuit by which midbrain dopamine neuronal activity modulates splenic immunity

Midbrain dopamine neurons are well-known to shape central nervous system function, yet there is growing evidence for their influence on the peripheral immune system. Here we demonstrate that midbrain dopamine neurons form a circuit to the spleen via a multi-synaptic pathway from the dorsal vagal complex (DVC) through the celiac ganglion. Midbrain dopamine neurons modulate the activity of D1- and D2-like dopamine receptor-expressing DVC neurons. In vivo activation of midbrain dopamine neurons induced dopamine release in the DVC and increased immediate early gene expression in both the DVC and celiac ganglion. Activation of this midbrain-to-spleen circuit reduced spleen weight and decreased naive CD4+ T-cell populations without affecting total T-cell numbers. These findings unveil a functional midbrain- DVC-celiac ganglion-spleen pathway, through which midbrain dopamine neurons modulate splenic immunity. These novel insights into the neural regulation of the immune system have important implications for diseases involving altered dopamine neurotransmission and highlight potential targets for immunotherapeutic interventions.

neuroscience↗

Reciprocal connectivity of the periaqueductal gray with the ponto-medullary respiratory network in rat.

Synaptic activities of the periaqueductal gray (PAG) can modulate or appropriate the respiratory motor activities in the context of behavior and emotion via descending projections to nucleus retroambiguus. However, alternative anatomical pathways for the mediation of PAG-evoked respiratory modulation via core nuclei of the brainstem respiratory network remains only partially described. We injected the retrograde tracer Cholera toxin subunit B (CT-B) in the pontine Kolliker-Fuse nucleus (KFn, n=5), medullary Botzinger (BotC, n=3) and pre-Botzinger complexes (pre-BotC; n=3), and the caudal raphe nuclei (n=3), and quantified the ascending and descending connectivity of the PAG. CT-B injections in the KFn, pre-BotC, and caudal raphe, but not in the BotC, resulted in CT-B-labeled neurons that were predominantly located in the lateral and ventrolateral PAG columns. In turn, CT-B injections into the lateral and ventrolateral PAG columns (n=4) yield the highest numbers of CT-B-labeled neurons in the KFn and far fewer numbers of labeled neurons in the pre-BotC and caudal raphe. Analysis of the relative projection strength revealed that the KFn shares the densest reciprocal connectivity with the PAG (ventrolateral and lateral columns, in particular). Overall, our data imply that the PAG may engage a distributed respiratory rhythm and pattern generating network beyond the nucleus retroambiguus to mediate downstream modulation of breathing. However, the reciprocal connectivity of the KFn and PAG suggests specific roles for synaptic interaction between these two nuclei that are most likely related to the regulation of upper airway patency during vocalization or other volitional orofacial behaviors. HighlightsO_LIThe lateral and ventrolateral PAG project to the primary respiratory network. C_LIO_LIThe Kolliker-Fuse nucleus shares the densest reciprocal connectivity with the PAG. C_LIO_LIThe Botzinger complex appears to have very little connectivity with the PAG. C_LI

neuroscience↗