Inner ear sensory hair cells convert mechanical
stimulations of their hair bundle into graded potentials which
modulate the tonic release of their neurotransmitter, glutamate.
This release occurs at synapses equipped with a dense ribbon
(Figure 1).
Figure
1a: Partially overlapping immuno¬reactivities
to the synaptic ribbon protein RIBEYE (green) and the
GluR2 subunit of AMPA receptors (red) at the basal pole
of an inner hair cell (blue, parvalbumin immuno¬reactivity).
Figure
1b: Biphoton microscopy calcium imaging measurement
(calcium green) at the inner hair cell synaptic complex
in response to iontophoretic application of glutamate.
The boundary of the hair cell have been shown.
This synapse is modulated by the central
nervous system via the terminals of the lateral olivocochlear
(LOC) efferent co-expressing several neurotransmitters (Fig.
2; acetylcholine, GABA, dopamine, enkephalins, dynorphins,
CGRP…). Despite its importance in the auditory function,
the cellular and molecular machineries underlying the function
of the inner hair cell synapse and its efferent modulation
are still largely unknown.
Figure 2: (A)
Immunoreactivities to vesicular Acetylcholine Transporter
(green) and tyrosine hydroxylase (red) at the base of
a parvalbumin-labelled inner hair cell (blue). Arrowheads
point on colocalized immunoreactivities identified by
a colocalization algorithm and the arrow points on a tyrosine
hydroxylase-only labelled terminal. (B) Dopamine suppresses
single unit activity of the auditory nerve fibers. (B,C,D)
Shown is a fiber coding for 8 kHz. A 10 min perfusion
with artificial perilymph (AP) containing 1mM dopamine
(DA) increase the threshold from 27 to 56 dB SPL (B),
reversibly decreases the spontaneous rate (C) and reduces
sound-driven activity (D). (From Ruel et
al., European
Journal of Neuroscience,
2001, 14: 977-986).
Our team works at elucidating the molecular
composition and functions of glutamate receptors and their
modulation by the lateral efferents in normal and pathological
cochlea. Based on electrophysiological and behavioural tests
(Fig. 3), we have demonstrated that some type of peripheral
tinnitus resulted from abnormal activation of NMDA receptors.
Figure 3 : Des
rats sont entraînés à exécuter
une tâche motrice (monter sur un mât) en
réponse à une stimulation sonore. En absence
de son, un animal normal n’exécute pas
la tâche. Si l’on induit un acouphène
avec du salicylate par exemple, l’animal exécute
la tâche alors qu’aucun son ne lui est présenté.
En fait, il se comporte comme s’il entendait un
son parce qu’il a un acouphène. Après
l’application locale d’antagonistes NMDA
MK 801, 7-CK, gacycliddine) au contact de la cochlée
(sur la fenêtre ronde), l’animal ne grimpe
plus au mat, parce qu’il n’a plus d’acouphène
(d’après Guitton et al., 2003).
Selected recent references:
Ruel J, Wang J, Demêmes D, Gobaille S, Puel
JL, Rebillard G. Dopamine transporter is essential
for the maintenance of spontaneous activity of auditory nerve
neurons and their responsiveness to sound stimulation. J.
Neurochem. 2006, 97: 190-200.
Eybalin M, Caicedo A, Renard N, Ruel J, Puel JL.
Transient Ca2+-permeable AMPA receptors in postnatal rat primary
auditory neurons. Eur. J. Neurosci. 2004, 20: 2981-2989.
Rebillard G, Ruel J, Nouvian R, Saleh H, Pujol R, Dehnes Y,
Raymond J, Puel JL, Devau G. Glutamate transporters
in the guinea pig cochlea : partial mRNA sequences, cellular
expression and functional implications. Eur. J. Neurosci.
2003, 17: 83-92.
Ruel J, Nouvian R, Gervais d’Aldin C, Pujol R, Eybalin
M, Puel JL. Dopamine inhibition of the auditory nerve
activity in the adult mammalian cochlea. Eur. J. Neurosci.
2001, 14: 977-986.
