P2 Receptor–Mediated Signaling in Spherical Bushy Cells of the Mammalian Cochlear Nucleus

Milenković, Ivan; Rinke, Ilka; Witte, Mirko; Dietz, Beatrice; Rübsamen, Rudolf

doi:10.1152/jn.00186.2009

Cited by 18 publications

(45 citation statements)

References 125 publications

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“…Morphological characterization of the recorded neurons was assessed (as previously shown for CN neurons; Milenkovic et al, 2009) by a post hoc labeling of biocytin-filled neurons with Cy2-conjugated streptavidin, according to the protocol described by (Bischofberger et al, 2006). After recording and fixation in 4% paraformaldehyde (PFA; in 0.1 M PBS, pH 7.3), the slices were washed (6 ϫ 5 min with TBS and 6 ϫ 5 min with TBS/0.3% Triton X-100) and incubated with Cy2-conjugated streptavidin (5 g/ml; Jackson ImmunoResearch) 2.5 h at RT.…”

Section: Methodsmentioning

confidence: 99%

“…(1) The slices were bulk labeled by incubation in ACSF supplemented with Fura 2 acetoxymethyl ester (10 M Fura-2 AM; Invitrogen) and 0.025% (w/v) pluronic acid, for 30 min at 37°C, as described previously (Milenkovic et al, 2009). (2) Alternatively, the measurement of intracellular calcium was performed simultaneously with whole-cell recordings.…”

Section: Fluorometric Ca 2ϩ Measurementsmentioning

confidence: 99%

“…However, purinergic signaling in the developing auditory system is not restricted to the organ of Corti. Recently, it was shown that activation of P2 purinoreceptors evokes APs in spherical bushy cells (SBCs) of the CN (Milenkovic et al, 2009). The modulatory effect of ATP on AP firing was observed before and shortly after the onset of hearing.…”

Section: Introductionmentioning

confidence: 99%

“…These data raised the question whether purinergic signaling might attune the activity of central auditory neurons and thereby contribute to developmental processes. In Mongolian gerbils, P2Rs show a differential distribution in the anteroventral cochlear nucleus (AVCN), i.e., they are present on SBCs, but not on stellate cells (Milenkovic et al, 2009). Purinergic signaling was also shown in neurons of the lateral superior olive (LSO) (Kreinest et al, 2009) and the medial nucleus of the trapezoid body (MNTB) (Watano et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Purinergic Modulation of Neuronal Activity in Developing Auditory Brainstem

Dietz

Jovanovic²,

Wielsch³

et al. 2012

Journal of Neuroscience

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In the developing nervous system, spontaneous neuronal activity arises independently of experience or any environmental input. This activity may play a major role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. In the auditory system, endogenously released ATP in the cochlea activates inner hair cells to trigger bursts of action potentials (APs), which are transferred to the central auditory system. Here we show the modulatory role of purinergic signaling beyond the cochlea, i.e., the developmentally regulated and cell-type-specific depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We assessed the effects of P2X receptors (P2XRs) on neuronal excitability from prehearing to early stages of auditory signal processing. Our results demonstrate that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with Ca 2ϩ signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous and also acoustically evoked activity in vivo, but these effects diminish with maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also evoked APs in the absence of glutamatergic transmission. In vivo recordings also revealed that endogenously released ATP in the CN contributes to neuronal firing activity by facilitating AP generation and prolonging AP duration. Given the enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable that purinergic signaling plays a specific role in the development of neuronal brainstem circuits.

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Section: Methodsmentioning

confidence: 99%

Section: Fluorometric Ca 2ϩ Measurementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Purinergic Modulation of Neuronal Activity in Developing Auditory Brainstem

Dietz

Jovanovic²,

Wielsch³

et al. 2012

Journal of Neuroscience

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“…The P2Y-activated cation nonselective, depolarizing conductance, can reinforce neuronal excitability at the level of the perikaryon and facilitate the propagation of action potentials along the nerve fibers. Interestingly, it has recently been shown that P2Y receptors, cooperating with a simultaneously evoked P2X conductance, increased the neuronal firing rates in the mammalian cochlear nucleus [73]. Moreover, control of intracellular calcium can modify neuronal survival (trophic effect), and the neurons can recognize environmental pathologic events by sensing dispersed ATP via purinergic receptors (damage confrontation), thereby invoking (so far unknown) self-defense intracellular mechanisms.…”

Section: Neuromodulation In Sgn/vgnmentioning

confidence: 99%

Purinergic signaling in cochleovestibular hair cells and afferent neurons

Ito

Dulon

2010

Purinergic Signalling

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Purinergic signaling in the mammalian cochleovestibular hair cells and afferent neurons is reviewed. The scope includes P2 and P1 receptors in the inner hair cells (IHCs) of the cochlea, the type I spiral ganglion neurons (SGNs) that convey auditory signals from IHCs, the vestibular hair cells (VHCs) in the vestibular end organs (macula in the otolith organs and crista in the semicircular canals), and the vestibular ganglion neurons (VGNs) that transmit postural and rotatory information from VHCs. Various subtypes of P2X ionotropic receptors are expressed in IHCs as well as P2Y metabotropic receptors that mobilize intracellular calcium. Their functional roles still remain speculative, but adenosine 5′-triphosphate (ATP) could regulate the spontaneous activity of the hair cells during development and the receptor potentials of mature hair cells during sound stimulation. In SGNs, P2Y metabotropic receptors activate a nonspecific cation conductance that is permeable to large cations as NMDG + and TEA + . Remarkably, this depolarizing nonspecific conductance in SGNs can also be activated by other metabotropic processes evoked by acetylcholine and tachykinin. The molecular nature and the role of this depolarizing channel are unknown, but its electrophysiological properties suggest that it could lie within the transient receptor potential channel family and could regulate the firing properties of the afferent neurons. Studies on the vestibular partition (VHC and VGN) are sparse but have also shown the expression of P2X and P2Y receptors. There is still little evidence of functional P1 (adenosine) receptors in the afferent system of the inner ear.

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