Biology subjects

Pauli, J. L.

Publications and source records attributed to Pauli, J. L..

8 recordsLinked to original sources

bioRxiv2026

Optogenetic activation of parabrachial tachykinin1 neurons drives nonphotic circadian entrainment

Mammalian circadian rhythms are primarily entrained by light, but nonphotic cues can also reorganize behavioral timing through mechanisms that remain poorly understood. Nocturnal foot shocks delivered to rodents while they forage away from the safety of their nesting area have been shown to entrain circadian behavioral rhythms and shift foraging and feeding to the daytime. To identify the neural circuits underlying this nonphotic fear entrainment, we optogenetically stimulated tachykinin 1-expressing neurons in the parabrachial nucleus (Tac1PBN) during the subjective night while the animals foraged outside of their nest, which recapitulated the total activity-rest phase switch in circadian behaviors induced by foot shocks. Furthermore, selective stimulation of Tac1PBN projections to the central amygdala (CeA) produced a significant but reduced phase shift compared to direct stimulation of Tac1PBN cell bodies. When Bmal1, a core clock gene, was conditionally deleted from the CeA, mice failed to fear-entrain, implicating the CeA molecular clock as a necessary component for fear entrainment. Together, these experiments demonstrate that activation of a defined neuronal population outside of the suprachiasmatic nucleus (SCN) can reorganize circadian behavior by engaging a non-SCN circadian oscillator network that requires an intact CeA molecular clock.

neuroscience↗

bioRxiv2026

Temporal single-cell profiling of the parabrachial Calca neurons reveals molecular dynamics driving nociplastic pain

Parabrachial Calca neurons are necessary for chronic pain and sufficient to drive nociplastic pain in mice, but how they sustain a pain state that outlasts its trigger is unknown. We performed temporal single-cell mRNA sequencing of the parabrachial nucleus (PBN) across the onset, chronic, and recovery phases of Calca neuron-driven tactile allodynia, using fixed-tissue profiling and reference-atlas registration to track molecularly defined populations over time. Activation broadly induced immediate-early genes, after which Calca neurons displayed changes in expression of genes that affect signaling and synaptic plasticity, with bidirectional changes that mirrored the onset and resolution of allodynia. The gene encoding brain-derived neurotrophic factor (Bdnf) remained persistently elevated in the chronic phase. BDNF infusion in the PBN prolonged allodynia, whereas blockade of its receptor (TrkB) attenuated it, and inactivating the Bdnf gene in Calca neurons abolished their hyperexcitability, attenuated allodynia, and relieved pain in a migraine model. These observations pinpoint BDNF as a driver of persistent nociplastic pain.

neuroscience↗

bioRxiv2026

Parabrachial oxytocin receptor-expressing neurons link social observation of distress to defensive behavior

The ability to detect and respond to threat signals in the environment, including those conveyed by the distress of a familiar social partner, is fundamental to survival and disrupted in a range of neuropsychiatric conditions. This study identifies oxytocin receptor (Oxtr)-expressing neurons within the lateral parabrachial nucleus (lPBN) of mice as a key node in the neural circuitry underlying threat-related and social behaviors. These Oxtr neurons are activated by aversive stimuli and by observing demonstrator mice in stressful situations, including foot shock or inflammatory pain. Chemogenetic inhibition of these neurons alters social proximity and pain contagion in observers without affecting general anxiety-like behavior. Inhibition also transiently suppresses non-social central sensitization. Direct activation of lPBNOxtr neurons with a selective Oxtr agonist is anxiogenic and results in increased tactile sensitivity. Together, these findings suggest that lPBNOxtr neurons are poised to integrate information about environmental threat, whether experienced directly or witnessed in a conspecific to coordinate appropriate defensive behavioral responses.

neuroscience↗

bioRxiv2026

A cholinergic eligibility trace facilitates amygdala plasticity in flavour avoidance learning

When an animal consumes a new food and consequently feels ill, it rapidly and robustly learns to avoid this food in the future, a form of learning termed conditioned flavour avoidance (CFA). Postingestive malaise often occurs long after novel food consumption, necessitating a neural mechanism that can facilitate plasticity between temporally distant events. Neuromodulators, acting through G-protein-coupled receptors (GPCRs) that can influence neuronal excitability on extended timescales, may facilitate this process. The projection of parabrachial (PB) Calca neurons to the central amygdala (CeA) is critical for formation of CFA. Here, we demonstrate that these neurons overlap with a PB population that releases acetylcholine (ACh) in the CeA. ACh is released in CeA during consumption of a novel solution and subsequent visceral malaise, consistent with a role in CFA acquisition. Two-photon calcium imaging in brain slices reveals that ACh widely activates CeA neurons and enhances glutamatergic responsivity on a timescale consistent with CFA learning. CRISPR-Cas9-mediated genetic knockdown and optogenetics demonstrate that ACh from PB facilitates CFA behavior. Large-scale neuronal recordings in the CeA along with our CRISPR approach reveal that loss of ACh signaling to CeA blocks key signatures of CFA-associated plasticity. Together, these data point to the cholinergic input from PB to central amygdala as a critical neuromodulatory signal that links activity over long timespans to facilitate associative learning in CFA.

neuroscience↗

bioRxiv2026

Parabrachial Ntsr1 neurons modulate food intake and anxiety through a projection to the ventromedial hypothalamus

The parabrachial nucleus (PBN) is an important hub located in the pons that relays sensory signals from peripheral regions. It is genetically diverse and contains many populations that modulate feeding and responses to threatening situations. A small Ntsr1-expressing population of neurons was identified that projects selectively to the ventromedial hypothalamus (VMH). The Ntsr1 neurons are scattered throughout the lateral PBN with a cluster of cells along the border to the nucleus of the lateral lemniscus (NLL) that overlap with Cck and Foxp2 expression. Chemogenetic activation of PBN Ntsr1 neurons results in Fos induction in Nr5a1 (SF1) and Bdnf neurons in the VMH. Activation of PBN Ntsr1 neurons or their terminals in the VMH reduces food intake after fasting and increases anxiety-like behaviors. In anxiogenic feeding assays, activation of PBN Ntsr1 neurons increases latency to feed as well as reducing food intake. Photometry showed that PBN Ntsr1-neuronal activity increases during anxiogenic situations but is suppressed during food consumption, suggesting a role in threat-induced suppression of feeding. Silencing PBN Ntsr1 neurons with tetanus toxin light-chain increased food intake and reduced anxiety. These findings reveal a genetically defined PBN to VMH circuit that responds to threats and suppresses feeding behavior. SignificanceThis study explored a population of Ntsr1 mRNA-expressing neurons in the parabrachial nucleus (PBN) that project selectively to the ventromedial hypothalamus (VMH). Stimulation of PBN Ntsr1 neurons and their terminals in the VMH decreased feeding and increased anxiety, results that resemble those achieved by activating VMH neurons, implicating the Ntsr1 neurons as part of the circuitry that controls feeding and anxiety. Because PBN Ntsr1 neurons are activated by aversive stimuli, they are posited to help mice suppress feeding in risky environments.

neuroscience↗

bioRxiv2024

Gustatory Thalamic Neurons Mediate Aversive Behaviors

The parvicellular part of the ventral posteromedial nucleus (VPMpc) of the thalamus, also known as the gustatory thalamus, receives input from the parabrachial nucleus and relays taste sensation to the gustatory (or insular) cortex. Prior research has focussed on the role of the VPMpc in relaying taste signals. Here we provide evidence showing that VPMpc also mediates aversive behaviors. By recording calcium transients in vivo from single neurons in mice, we show that neurons expressing cholecystokinin and the mu-opioid receptor in the VPMpc respond to various noxious stimuli and fear memory. Chemogenetic and optogenetic activation of these neurons enhances the response to aversive stimuli, whereas silencing them attenuates aversive behaviors. The VPMpc neurons directly innervate neurons in the insular cortex and rostral lateral amygdala. This study expands the role of the VPMpc to include mediating aversive and threating signals to the insular cortex and lateral amygdala.

neuroscience↗

bioRxiv2023

Parabrachial Calca neurons drive nociplasticity

Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBN Calca neurons from releasing neurotransmitter or directly stimulating them we demonstrate that activation of Calca neurons is both necessary for the manifestation of chronic pain after nerve ligation and is sufficient to drive nociplasticity in wild-type mice. Aversive stimuli such as exposure to nitroglycerin, cisplatin, or LiCl can drive nociplasticity in a Calca-neuron-dependent manner. Calcium fluorescence imaging reveals that nitroglycerin activates PBN Calca neurons and potentiates their responses to mechanical stimulation. The activity and excitability of Calca neurons increased for several days after aversive events, but prolonged nociplasticity likely occurs in downstream circuitry.

neuroscience↗

bioRxiv2022

Molecular and Anatomical Characterization of Parabrachial Neurons and Their Axonal Projections

The parabrachial nucleus (PBN) is a major hub that receives sensory information from both internal and external environments. Specific populations of PBN neurons are involved in behaviors including food and water intake, pain sensation, breathing regulation, as well as learning and responding appropriately to threatening stimuli. However, it is unclear how many PBN neuron populations exist and how different behaviors may be encoded by unique signaling molecules or receptors. Here we provide a repository of data on the molecular identity, spatial location, and projection patterns on dozens of PBN neuron subclusters. Using single-cell RNA sequencing, we identified 21 subclusters of neurons in the PBN and neighboring regions. Multiplexed in situ hybridization showed many of these subclusters are localized to distinct PBN subregions. We also describe two major ascending pathways that innervate distinct brain regions by analyzing axonal projections in 21 Cre-driver lines of mice. These results are all publicly available for download and provide a foundation for further interrogation of PBN functions and connections.

neuroscience↗