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Activation of muscarinic cholinergic receptors stimulates inositol phosphates synthesis in the developing avian
S Bartolami1, E Mayat, W R Lippe
1INSERM-U 254, Laboratoire de Neurobiologie de l'Audition, Hôpital St Charles, Montpellier, France.
Insights
Inositol phosphates (IPs) synthesis in the developing chick cochlea correlates with neuronal plasticity. This enhanced IPs formation, triggered by muscarinic agonists, is not unique to rats, suggesting a conserved mechanism in vertebrates.
Area of Science:
- Neuroscience
- Developmental Biology
- Auditory System Research
Background:
- Previous studies identified muscarinic agonist-induced inositol phosphates (IPs) synthesis in the rat cochlea, peaking at postnatal day 12.
- This peak response in rats coincides with efferent synaptogenesis at the outer hair cell level, suggesting a link to neuronal plasticity.
- The species-specificity of this correlation between cochlear neuronal plasticity and enhanced IPs formation remained unknown.
Purpose of the Study:
- To investigate if the correlation between cochlear plasticity and enhanced IPs formation is a general feature of developing vertebrate cochleas.
- To examine the temporal dynamics of inositol phosphates synthesis in the developing chick cochlear duct.
Main Methods:
- Measured the accumulation of (3H)-IPs induced by carbachol in developing chick cochlear ducts from embryonic day 8 to post-hatching day 20.
- Utilized LiCl to measure IPs accumulation and carbachol (1 mM) as the muscarinic agonist.
- Investigated the role of muscarinic receptors by testing atropine's inhibitory effects on IPs synthesis.
Main Results:
- Carbachol significantly increased IPs formation across all tested ages in chick cochlear ducts.
- IPs accumulation was highest at embryonic day 8 (1854% of basal) and decreased to a steady-state level (294%) by post-hatching day 13.
- A transient surge in IPs synthesis occurred between embryonic days 15-19, peaking at embryonic day 16 (757% of control), coinciding with efferent innervation maturation and inhibited by atropine.
Conclusions:
- The study demonstrates that enhanced inositol phosphates synthesis in the cochlea, linked to neuronal plasticity, is not species-specific to rats.
- Findings suggest a conserved correlation between cochlear plasticity and muscarinic agonist-induced IPs synthesis in developing vertebrates.
- The transient increase in IPs synthesis during specific developmental windows highlights its potential role in critical stages of auditory system maturation.
Abstract:
We previously reported that the inositol phosphates (IPs) synthesis is induced by muscarinic agonists in the rat cochlea and that this stimulation is maximal at postnatal day 12. This peak response is concomitant with the onset of the efferent synaptogenesis at the outer hair cell level. Whether the correlation between this neuronal plasticity and the enhanced IPs formation is unique to the rat or a general feature of the developing vertebrate cochlea is not known. To examine this question, we measured, in the presence of LiCl, the accumulation of (3H)-IPs induced by carbachol, in the developing chick cochlear duct during a period ranging from embryonic day (E) 8 to post-hatching day (P) 20. Carbachol (1 mM) causes a significant increase of IPs formation relative to basal values at all ages. This IPs accumulation is maximal at E8 (1854% of the basal level), then, rapidly decreases until P13 when it reaches a steady-state level of 294% of the basal level. Strikingly, this gradual decline in IPs formation is interrupted between E15 and E19, by a transient increase in IPs synthesis. This rise peaks at E16 with a stimulation value of 757% of the control level. This maximal stimulation is inhibited by atropine in a dose-dependent manner, as is the case at E9, suggesting the involvement of muscarinic receptors. Interestingly, the occurrence of the peak response is concomitant with the plastic events associated with the maturation of the efferent innervation of the cochlear duct. Thus, these results suggest that there may be a correlation between cochlear plasticity and enhanced IPs synthesis, which is not species-specific.(ABSTRACT TRUNCATED AT 250 WORDS)