Nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic (DA) neurons have long been considered as potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine and cocaine addiction or Parkinson's disease. However, DA express mRNAs coding most, if not all, neuronal nAChR subunits, subunit composition functional nAChRs has difficult to establish. Immunoprecipitation experiments performed on mouse striatal extracts allowed us identify...

The neurons of the locus ceruleus are responsible for most noradrenergic innervation in brain and nicotine potentiates noradrenaline release from their terminals. Here we investigated diversity subcellular distribution nicotinic acetylcholine receptors (nAChRs) both somatically, by combining single-cell reverse transcription–PCR with electrophysiological characterization, at level nerve terminals, conducting efflux experiments. proportion expressing subunit mRNAs varied 100% (β2) to 3% (α2)....

A deficit in inhibition the spinal dorsal horn has been proposed to be an underlying cause of exaggerated cutaneous sensory reflexes observed newborn rats. However, developmental shift transmembrane anion gradient, potentially affecting outcome GABA transmission, was shown completed within 1 week after birth cord, apparent disparity with observation that reflex hypersensitivity persists throughout first 2-3 postnatal weeks. To further investigate this issue, we used several approaches assess...

Endogenous acetylcholine is an important modulator of sensory processing, especially at the spinal level, where nociceptive (pain-related) stimuli enter central nervous system and are integrated before being relayed to brain. To decipher organization local cholinergic circuitry in dorsal horn, we used transgenic mice expressing enchanced green fluorescent protein specifically neurons (ChAT::EGFP) characterized morphology, neurochemistry, firing properties sparse population interneurons this...

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, CS descending projection plays major role in motor command, results from direct and indirect control cord pre-motor interneurons as well motoneurons. But addition, this also involved selective modulation sensory feedback. Despite recent evidence confirms that projections drive distinct segmental neural circuits are part pathways, little known about networks engaged by (CST),...

Nicotinic agonists have well-documented antinociceptive properties when administered subcutaneously or intrathecally in mice. However, secondary mild to toxic effects are observed at analgesic doses, as a consequence of the activation large family differentially expressed nicotinic receptors (nAChRs). In order elucidate action on spinal local circuits, we investigated expression and function nAChRs functionally identified neurons neonate mice cord. Molecular markers, amplified single-cell...

It is generally assumed that the main function of corticospinal tract (CST) to convey motor commands bulbar or spinal motoneurons. Yet CST has also been shown modulate sensory signals at their entry point in cord through primary afferent depolarization (PAD). By sequentially investigating different routes corticofugal pathways electrophysiological recordings and an intersectional viral strategy, we here demonstrate modulation mice belong segregated paths within CST. Sensory executed...

The spinal serotoninergic projection from the raphe magnus has been shown to modulate nociceptive inputs, and activation of this mediates nicotine-elicited analgesia. Here, we investigate interactions between cholinergic systems in cord, by conducting serotonin [5-hydroxytryptamine (5-HT)] efflux experiments on mouse slices. At least three populations nicotinic receptors are distinguished that affect 5-HT release. first could be directly located terminals, is insensitive nanomolar...

Sensory input to supraspinally projecting lamina I (LI) neurons arises both directly from primary afferents and via intrinsic the spinal dorsal horn. The types of presynaptic those projection remain poorly known. To address this question we used retrogradely transported adenoviral vectors encoding green fluorescent protein (GFP) a GFP-TTC (fragment C tetanus toxin) fusion protein, labeling respectively spinoparabrachial them. expression GFP by infected labeled entire dendritic tree, enabling...

Endogenous acetylcholine (ACh) is a well-known modulator of nociceptive transmission in the spinal cord rodents. It arises mainly from sparse population cholinergic interneurons located dorsal horn cord. This was thought to be absent monkey, what might suggest that ACh would not relevant clinical target for pain therapy. In humans, however, responses can modulated by ACh, as evidenced increasingly used analgesic procedure (for postoperative and labor patients) consisting epidural injection...

Although cholinergic drugs are known to modulate nociception, the role of endogenous acetylcholine in nociceptive processing remains unclear. In current study, we evaluated transmission through spinal β(2)-subunit-containing nicotinic receptors control thresholds. We show that mechanical and thermal thresholds significantly lowered β(2)(∗)-knockout (KO) mice. Using antagonists these mice, demonstrate β(2)(∗)-nAChRs responsible for tonic inhibitory at level. further hypothesized β(2)(∗)-nAChR...

Recent studies carried out on amyotrophic lateral sclerosis patients suggest that the disease might initiate in motor cortex and spread to its targets along corticofugal tracts. In this study, we aimed test hypothesis of experimentally.

Abstract Plasticity of inhibitory transmission in the spinal dorsal horn (SDH) is believed to be a key mechanism responsible for pain hypersensitivity neuropathic syndromes. We evaluated this plasticity by recording responses mechanical stimuli silent neurons (nonspontaneously active [NSA]) and showing ongoing activity (spontaneously [SA]) SDH control nerve-injured mice (cuff model). The SA NSA represented 59% 41% recorded neurons, respectively, were predominantly wide dynamic range (WDR)...

Endogenous acetylcholine (ACh) is an important modulator of nociceptive sensory processing in the spinal cord. An increased level ACh induces analgesia both humans and rodents while interfering with cholinergic signaling allodynic, demonstrating that a basal tone modulates responses naïve animals. The plasticity undergone by this system chronic pain situation unknown, mere presence neuropathic animals controversial. We have addressed these issues mice through behavioral experiments,...

Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease of adulthood that affects voluntary motricity and rapidly leads to full paralysis death. ALS arises from the combined degeneration motoneurons in spinal cord brain stem, responsible for muscle denervation, corticospinal projection neurons (CSN), emergence upper motor neuron syndrome. Recent studies carried on patients suggest may initiate cortex spread its targets. However, this “corticofugal hypothesis” has...

Nicotinic agonists have well-documented antinociceptive properties when administered subcutaneously or intrathecally in mice. However, secondary mild to toxic effects are observed at analgesic doses, as a consequence of the activation large family differentially expressed nicotinic receptors (nAChRs). In order elucidate action on spinal local circuits, we investigated expression and function nAChRs functionally identified neurons neonate mice cord. Molecular markers, amplified single-cell...

Abstract At the spinal cord level, a tone of endogenous acetylcholine (ACh) modulates nociceptive sensory processing. Increasing level ACh induces analgesia in naïve animals or situation acute pain clinics, but whether this is still case situations models chronic controversial. Here, we demonstrate persistence, and even increased impact analgesic cholinergic acting through nicotinic receptors neuropathic mice. The neuropathy does not affect number properties dorsal horn neurons, proposed to...

Abstract It is generally assumed that the main function of corticospinal tract (CST) to convey motor commands bulbar or spinal motoneurons. Yet CST has also been shown modulate sensory signals at their entry point in cord, through presynaptic inhibition. By sequentially investigating different routes corticofugal pathways electrophysiological recordings and an intersectional viral strategy, we here demonstrate modulation mice belong segregated paths within CST. Sensory excuted exclusively by...