Audition Promenade round Cochlea autour Cochlée oreille ear organ of Corti oreille ear CRIC Montpellier Remy Pujol U254

	Innervation of the organ of Corti
	Overview / Spiral ganglion / Neurotransmitters
	Scientific concept : M. Eybalin
	Drawings: S. Blatrix

Almost unknown in the early 90s, cochlear neurochemistry is now well documented at molecular anatomical level (refs. c3, c4, c5); in addition, physiological and pharmacological studies are now well developed.

Neurotransmitters at IHC synapses

Glutamate as the afferent neurotransmitter
	Glutamate (Glu) is the main candidate for neurotransmission at synapses between IHC and radial (type I) afferent dendrites. A large variety of findings support this idea, such as this specific autoradiographic labeling (asterisk) of the IHC, after tritiated glutamine loading (from ref. c.11).
	Molecular pharmacology is highlighting the main (sub)types of receptors (ref.c20). Among ionotropic receptors, GLUR2/3 of the AMPA type are the most active at the postsynapse under physiological conditions (ref.c16), and NR1 of NMDA type under noisy conditions (ref. c15).

Glutamate is a fast excitatory neurotransmitter, ideal for the IHC-auditory nerve synapse. However, due to its excitotoxic properties, it is responsible for spiral ganglion neuron pathologies.

Metabotropic receptors are also found, such as mR1, of which mRNA is expressed (see in situ-hybridisation picture on the right) both postsynaptically (in spiral ganglion neurons) and presynaptically (in the IHC, red arrows).

The white arrow points to a non-specific labelling of the tectorial membrane.

S.Safieddine

Lateral efferent neurotransmitters

M.Eybalin

As shown in the top schematic drawing, the lateral efferent endings contain a cocktail of neurotransmitters (see recent reviews).

These pictures show an immunochemical co-localisation of metenkephalin (green) and dopamine (TH, red). White arrows point to co-localisation in efferent varicosities.

Immunocytochemistry of lateral efferent synapses

M.Eybalin	R.Pujol
The lateral efferent endings, synapsing (red arrowheads) with the radial afferent dendrites below the IHCs, contain a cocktail of neurotransmitters (see recent reviews): ACh (as in ChAT-labelled endings in left picture), DA, Gaba, and neuropeptides - enkephalins (as in MET-labelled ending in right picture), and dynorphins, CGRP. Some of them, such as DA, are obviously there to protect and/or help repair the afferent glutamatergic synapse (blue arrows). scale bars: 1 µm (left) and 0.5 µm (right).

Neuroransmitters at OHC synapses
	The neurotransmitter at the OHC-spiral (type II) afferent synapse is not known: perhaps glutamate but mediated via different types of receptors?

Medial efferent neurotransmitters

M.Eybalin /R.Pujol

For the medial efferent synapses ACh (as in the huge ChAT-labelled ending on the left) looks to be the main candidate with, at the postsynapse, a new (alpha 9) type of nicotinic receptor which possesses some muscarinic properties.

Gaba is possibly co-localised with ACh in most efferent synapses in the mid- and apical cochlea. Moreover, CGRP and ATP may well act as neuromodulators.

scale bar: 0.5 µm