Biology subjects

Decosterd, I.

Publications and source records attributed to Decosterd, I..

4 recordsLinked to original sources

bioRxiv2023

Kir2.1 modulation in macrophages sensitises dorsal root ganglion neurons through TNF secretion after nerve injury

Macrophages and satellite glial cells are found between injured and uninjured neurons in the lumbar dorsal root ganglia (DRG). We explored the mechanism of neuro-immune and neuron-glia crosstalk leading to hyperexcitability of DRG neurons. After spared nerve injury (SNI), CX3CR1+ resident macrophages became activated, proliferated and increased inward-rectifying potassium channel Kir2.1 currents. Conditioned medium (CM) by macrophages, obtained from DRG of SNI mice, sensitised small DRG neurons from naive mice. However, treatment with CM from GFAP+ glial cells did not affect neuronal excitability. When subjected to this macrophage-derived CM, DRG neurons had increased spontaneous activity, current-evoked responses and voltage-gated NaV1.7 and NaV1.8 currents. Silencing Kir2.1 in macrophages after SNI prevented the induction of neuronal hyperexcitability from their CM. Blocking vesicular exocytosis or soluble tumour necrosis factor (TNF) in CM or interfering with the downstream intracellular p38 pathway in neurons, also prevented neuronal hyperexcitability. Blocking protein trafficking in neurons reduced the effect of CM, suggesting that the hyperexcitable state resulted from changes in NaV channel trafficking. These results suggest that DRG macrophages, primed by peripheral nerve injury, contribute to neuron-glia crosstalk, NaV channel dysregulation and neuronal hyperexcitability implicated in the development of neuropathic pain. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/545843v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@2591acorg.highwire.dtl.DTLVardef@7ebc82org.highwire.dtl.DTLVardef@8a2c4corg.highwire.dtl.DTLVardef@1624244_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in juvenile rats

Development of self-regulatory competencies during adolescence is partially dependent on normative brain maturation. Here we report that juvenile rats as compared to adults exhibit impulsive and compulsive-like behavioral traits, the latter being associated with lower expression of mRNA levels of the immediate early gene zif268 in the anterior insula (AI). This observation suggests that deficits in AI function in juvenile rats could explain their immature pattern of interoceptive cue integration in rational decision-making and compulsive phenotype. In support of this, here we report hypoexcitability of juvenile layer-V pyramidal neurons in the AI, concomitant with reduced glutamatergic synaptic input to these cells. Chemogenetic activation of the AI attenuated the compulsive trait suggesting that delayed maturation of the AI results in suboptimal integration of sensory and cognitive information in adolescents and this contributes to inflexible behaviors in specific conditions of reward availability.

neuroscience↗

bioRxiv2021

Cortico-autonomic local arousals and heightened somatosensory arousability during NREM sleep of mice in neuropathic pain

Chronic pain patients frequently suffer from sleep disturbances. Improvement of sleep quality alleviates pain, but neurophysiological mechanisms underlying sleep disturbances require clarification to advance therapeutic strategies. Chronic pain causes high-frequency electrical activity in pain-processing cortical areas that could disrupt the normal process of low-frequency sleep rhythm generation. We found that the spared-nerve-injury (SNI) mouse model, mimicking human neuropathic pain, had preserved sleep-wake behavior. However, when we probed spontaneous arousability based on infraslow continuity-fragility dynamics of non-rapid-eye-movement sleep (NREMS), we found more numerous local cortical arousals accompanied by heart rate increases in hindlimb primary somatosensory, but not in prelimbic, cortices of SNI mice. Closed-loop mechanovibrational stimulation revealed higher sensory arousability in SNI. Sleep in chronic pain thus looked preserved in conventional measures but showed elevated spontaneous and evoked arousability. Our findings develop a novel moment-to-moment probing of NREMS fragility and propose that chronic pain-induced sleep complaints arise from perturbed arousability.

physiology↗

bioRxiv2020

Oxytocin Acts on Astrocytes in the Central Amygdala to Promote a Positive Emotional State

Oxytocin orchestrates social and emotional behaviors through modulation of neural circuits in brain structures such as the central amygdala (CeA). The long-standing dogma is that oxytocin signaling in the central nervous system occurs exclusively via direct actions on neurons. However, several findings over the last decades showed that astrocytes actively participate in the modulation of neuronal circuits. Here, we investigate the degree of astrocytes involvement in oxytocin functions. Using astrocyte specific gain and loss of function approaches, we demonstrate that CeA astrocytes not only directly respond to oxytocin, but are actually necessary for its effects on neuronal circuits and ultimately behavior. Our work identifies astrocytes as a crucial cellular substrate underlying the promotion of a positive emotional state by oxytocin. These results further corroborate that astrocytes are key regulators of neuronal circuits activity by responding to specific neuropeptidergic inputs, and opens up new perspectives to understand how neuromodulators gate brain functions.

neuroscience↗