Development of adult-type inhibitory glycine receptors in the central auditory system of rats

Friauf, Eckhard; Hammerschmidt, Brigitte; Kirsch, Joachim

doi:10.1002/(sici)1096-9861(19970818)385:1<117::aid-cne7>3.0.co;2-5

Cited by 101 publications

(81 citation statements)

References 68 publications

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“…During the first 1.5 weeks after birth, glycine receptor mRNA and protein expression increases in the cochlear nuclei (24,34). This increase parallels the presynaptic glycine receptor localization that we have observed and coincides with an increase in glycine immunoreactivity of the glycinergic MNTB neurons themselves (35).…”

Section: Discussionsupporting

confidence: 85%

Reciprocal developmental regulation of presynaptic ionotropic receptors

Tureček

Trussell

2002

Proc. Natl. Acad. Sci. U.S.A.

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Activation of ionotropic glycine receptors potentiates glutamate release in mature calyceal nerve terminals of the rat medial nucleus of the trapezoid body, an auditory brainstem nucleus. In young rats, glycine and its receptors are poorly expressed. We therefore asked whether GABA (␥-aminobutyric acid) might play a larger role than glycine in the regulation of glutamate release in the absence of glycine receptors. Indeed, in rats younger than postnatal day 11 (P11), and before the onset of hearing, calyces expressed high levels of ionotropic GABAA receptors but few glycine receptors. Isoguvacine, a selective agonist at GABAA receptors, strongly enhanced excitatory postsynaptic currents in young rats but had little effect in rats older than P11. Down-regulation of presynaptic GABAA receptors did not reflect global changes in receptor expression, because the magnitude of GABA and glycine responses was similar at P13 in the parent-cell bodies of the calyces, the bushy cells of the cochlear nucleus. In outside-out patches excised from the nonsynaptic face of calyces, GABA and glycine evoked singlechannel currents consistent with the properties of postsynaptic GABAA and glycine receptors. Inhibitory GABAB receptors were present on the calyx at all developmental stages examined. Thus, GABA initially acts on two receptor subtypes, both promoting and inhibiting glutamate release. With age, the former role is transferred to the glycine receptor during the period in which postsynaptic glycinergic transmission is acquired. L igand-gated ion channels (ionotropic receptors) aggregate in subsynaptic membrane shortly after pre-and postsynaptic cells come in close contact (1-4). During maturation of the synapse, changes often occur in the subtypes of postsynaptic receptor (5, 6). Recently, it has become clear that many synapses contain presynaptic ionotropic receptors, such as glutamate, GABA A (␥-aminobutyric acid type A), or acetylcholine receptors, whose activation regulates transmitter release in response to presynaptic action potentials (7). Unlike many postsynaptic receptors, it is not known whether presynaptic receptors are expressed in parallel with the development of their corresponding transmitter systems. This problem is accentuated by the fact that presynaptic receptors generally are not directly apposed to presynaptic terminals (axo-axonic synapses) but, rather, are activated by ''spillover'' of transmitter from distant terminals (8, 9). Moreover, it is not known whether these receptors are selectively targeted to axon terminals or, instead, appear in proportion to global changes in receptor expression over the entire neuron.The calyx of Held is a large glutamatergic nerve terminal found on neurons of the medial nucleus of the trapezoid body (MNTB), a brainstem auditory relay nucleus. Postsynaptic neurons in MNTB are glycinergic and supply fast inhibition to diverse targets in the superior olivary complex. We previously have shown that presynaptic glycine receptors are expressed on the calyx terminal and that acti...

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Section: Discussionsupporting

confidence: 85%

Reciprocal developmental regulation of presynaptic ionotropic receptors

Tureček

Trussell

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…On the level of SG neurons, a dot-like staining pattern, which is typical of glycine receptors in CNS neurons (Friauf et al 1997;Becker et al 1991), was observed for GlyR 3 (Fig. 5a, open arrows) and gephyrin protein (Fig.…”

Section: Mrna Localization Of Glycine Receptors and Gephyrin By In Simentioning

confidence: 86%

“…6c-e) and in OHCs (Fig. 6c, d, f) of the adult (>P21) rat cochlea, reminiscent of postsynaptic GlyR clusters in the cell membrane of CNS neurons (Friauf et al 1997;Becker et al 1991).…”

Section: Glyr and Gephyrinmentioning

confidence: 92%

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Expression of glycine receptors and gephyrin in the rat cochlea

Dlugaiczyk

Singer

Schick

et al. 2008

Histochem Cell Biol

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The cochlear efferent feedback system exerts direct impact on cochlear nerve activity and balances interaural sensitivity. So far, acetylcholine, GABA and dopamine are known to be transmitters of the inhibitory efferent system. Despite the wealth of information about glycinergic neurotransmission in the central auditory system, the inhibitory glycine receptor (GlyR) has not yet been regarded as a target molecule of efferent transmission in the cochlea. Using RT-PCR, in situ hybridization and immunohistochemistry, we show that GlyRalpha3, GlyRbeta and gephyrin are expressed in the organ of Corti and spiral ganglion neurons. Furthermore, two alternative splice variants of GlyRalpha3, corresponding to the long (alpha3_L) and short (alpha3_K) human isoforms, could be distinguished. The localization of glycine receptors below inner hair cells and in outer hair cells of the adult cochlea suggests that these inhibitory receptors may serve as target molecules of the efferent olivocochlear bundle.

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“…This switch is synchronized with the maturation of calyceal transmission (Awatramani et al, 2003). However, anatomical studies suggest that the expression of the "adult" glycine receptor subunit (␣1) does not peak until ϳ3 weeks after birth (Friauf et al, 1997;Piechotta et al, 2001). This led us to investigate the properties of inhibition in older animals.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Control at a Synaptic Relay

Awatramani

Tureček²,

Trussell³

2004

J. Neurosci.

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The mammalian medial nucleus of the trapezoid body (MNTB) harbors one of the most powerful terminals in the CNS, the calyx of Held. The mechanisms known to regulate this synaptic relay are relatively ineffective. Here, we report the presence of a remarkably robust and fast-acting glycinergic inhibitory system capable of suppressing calyceal transmission.Evoked glycinergic IPSCs were relatively small in 2-week-old rats, an age by which calyceal maturation has reportedly neared completion. However, by postnatal day 25 (P25), glycinergic transmission had undergone a vigorous transformation, resulting in peak synaptic conductances as high as 280 nS. These are comparable with glutamatergic conductances activated by calyceal inputs. Decay kinetics for IPSCs were severalfold faster than for glycinergic synaptic events reported previously. At physiological temperatures in P25 rats, IPSCs decayed in ϳ1 msec and could be elicited at frequencies up to 500 Hz. Moreover, EPSPs triggered by glutamatergic signals derived from the calyx or simulated by conductance clamp were suppressed when preceded by simulated glycinergic IPSPs. The matching of excitatory transmission in the calyx of Held by a powerful, precision inhibitory system suggests that the relay function of the MNTB may be rapidly modified during sound localization.

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Development of adult-type inhibitory glycine receptors in the central auditory system of rats

Cited by 101 publications

References 68 publications

Reciprocal developmental regulation of presynaptic ionotropic receptors

Reciprocal developmental regulation of presynaptic ionotropic receptors

Expression of glycine receptors and gephyrin in the rat cochlea

Inhibitory Control at a Synaptic Relay

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