Biology subjects

Lorsung, R.

Publications and source records attributed to Lorsung, R..

4 recordsLinked to original sources

bioRxiv2026

Sex Differences in Bed Nucleus of the Stria Terminalis Response to Calcitonin Gene-Related Peptide

Women are disproportionately affected by chronic pain, yet the neural mechanisms underlying sex differences in affective pain processing remain incompletely understood. The bed nucleus of the stria terminalis (BNST), a sexually dimorphic structure implicated in aversion and chronic pain, receives dense input from aversive calcitonin gene-related peptide (CGRP)-expressing neurons arising from the parabrachial nucleus (PBN). Although CGRP signaling has been implicated in sex differences in clinical pain conditions, whether CGRP transmission within the PBN[->]BNST pathway is sexually dimorphic has not been determined. Here, we tested the hypothesis that CGRP signaling in the BNST differs between sexes. Contrary to our prediction, PBN CGRP neurotransmitter release in the BNST was sex-independent. However, CGRP neuromodulation of BNST excitability exhibited sex-dependent features. While CGRP potentiated PBN[->]BNST glutamatergic signaling in both sexes, spontaneous inhibitory signaling was selectively increased in males. Together, these findings indicate that sex differences in this circuit arise not from differential peptide release, but from downstream modulation of inhibitory tone, biasing female BNST neurons toward greater excitation. Such circuit-specific sex differences may contribute to the enhanced susceptibility of females to affective components of chronic pain and highlight targets for sex-informed therapeutic interventions.

neuroscience↗

bioRxiv2026

Structural Components for Calcitonin Gene-Related Peptide Signaling to Oligodendrocyte Precursor Cells

Oligodendrocyte precursor cells (OPCs) are unique glial cells that communicate bidirectionally with neurons. Neuronal inputs drive various OPC behaviors, including proliferation and differentiation, immunomodulation, blood brain barrier regulation, synapse engulfment and axonal remodeling. OPCs are implicated in numerous stress and pain conditions, where their involvement is likely driven by neuronal activity (ie. neurotransmitter and neuropeptide signaling). One neuropeptide causally involved in chronic pain and stress conditions is calcitonin gene-related peptide (CGRP). Here, we tested the hypothesis that OPCs receive direct inputs from CGRP-containing neurons in the adult brain. Using RNAscope, immunofluorescence and analysis of single-cell datasets, we find that OPCs express receptors for CGRP and we identify close spatial contacts between CGRP and OPCs, with nearly half of CGRP puncta occurring within 1 {micro}m of an OPC. Some of these contacts appear to be synaptic, with CGRP-OPC contacts colocalizing with the presynaptic protein Bassoon and the postsynaptic protein PSD-95. This work suggests the presence of both diffuse and more direct forms of CGRP signaling to OPCs, raising the importance of future experiments to identify both the mode of CGRP release onto OPCs and the functional effects of these different contact types.

neuroscience↗

bioRxiv2024

Sex differences in central amygdala glutamate responses to calcitonin gene-related peptide

Women are disproportionately affected by chronic pain compared to men. While societal and environmental factors contribute to this disparity, sex-based biological differences in the processing of pain are also believed to play significant roles. The central lateral nucleus of the amygdala (CeLC) is a key region for the emotional-affective dimension of pain, and a prime target for exploring sex differences in pain processing since a recent study demonstrated sex differences in CGRP actions in this region. Inputs to CeLC from the parabrachial nucleus (PB) play a causal role in aversive processing, and release both glutamate and calcitonin gene-related peptide (CGRP). CGRP is thought to play a crucial role in chronic pain by potentiating glutamatergic signaling in CeLC. However, it is not known if this CGRP-mediated synaptic plasticity occurs similarly in males and females. Here, we tested the hypothesis that female CeLC neurons experience greater potentiation of glutamatergic signaling than males following endogenous CGRP exposure. Using trains of optical stimuli to evoke transient CGRP release from PB terminals in CeLC, we find that subsequent glutamatergic responses are preferentially potentiated in CeLC neurons from female mice. This potentiation was CGRP-dependent and involved a postsynaptic mechanism. This sex difference in CGRP sensitivity may explain sex differences in affective pain processing. Significance statementThe central lateral nucleus of the amygdala (CeLC) receives a dense projection from parabrachial nucleus (PB) neurons that corelease calcitonin gene-related peptide (CGRP) and glutamate following aversive stimuli. This PBCGRP[->]CeLC projection plays a causal role in chronic pain. We show that endogenous CGRP release potentiates glutamate signaling in female, but not male, CeLC neurons. In the context of previous work in male CeLC, this suggests that that females are more sensitive to even transient CGRP release events. Understanding how this sex difference in CGRP sensitivity arises could enhance strategies for treating chronic pain in both women and men.

neuroscience↗

bioRxiv2023

Sex differences in the role of parabrachial in nociception and pain in awake mice

The parabrachial nuclear complex (PBN) is a nexus for aversion, and for the sensory and affective components of pain perception. We have previously shown that, during chronic pain, PBN neurons in anesthetized rodents have amplified activity. We report a method to record from PBN neurons of behaving, head-restrained mice, while applying reproducible noxious stimuli. We find that both spontaneous and evoked activity are higher in awake animals, compared to urethane anesthetized mice. Fiber photometry of calcium responses from CGRP-expressing PBN neurons demonstrates that these neurons respond to nociceptive stimuli. In both males and females with neuropathic or inflammatory pain, responses of PBN neurons remain amplified for at least 5 weeks, in parallel with increased pain metrics. We also show that PBN neurons can be rapidly conditioned to respond to innocuous stimuli, after pairing with nociceptive stimuli. Finally, we demonstrate that changes in PBN neuronal activity are correlated with changes in arousal, measured as changes in pupil diameter. Significance StatementThe parabrachial complex is a nexus of aversion, including pain. We report a method to record from parabrachial nucleus neurons of behaving mice, while applying reproducible noxious stimuli. This allowed, for the first time, tracking the activity of these neurons over time in animals with neuropathic or inflammatory pain. It also allowed us to show that the activity of these neurons correlates with arousal states, and that these neurons can be conditioned to respond to innocuous stimuli.

neuroscience↗