Convulsants Acting at the Inhibitory Glycine Receptor

Becker, Cord‐Michael

doi:10.1007/978-3-642-85117-9_15

Cited by 16 publications

(14 citation statements)

References 172 publications

(188 reference statements)

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“…The inhibitory actions of glycine receptors (GlyRs) sensitive to strychnine acting as competitive antagonist (Young and Snyder, 1973) lead to an increased chloride conductance through a ligand-gated ion channel resulting in hyperpolarization of the postsynaptic membrane (Bormann et al, 1987). The strychninebinding site of the GlyR protein complex is located in the ␣1-␣4-subunit variants, which constitute all GlyR isoforms (Becker, 1992). Because sensitivity to strychnine is indicative of ␣-subunits being present, we decided to study whether cuneate neurons possessing GlyRs were differently distributed in the cutaneous core or cluster region relative to the rvCN and/or the mvCN.…”

Section: Methodsmentioning

confidence: 99%

Processing Afferent Proprioceptive Information at the Main Cuneate Nucleus of Anesthetized Cats

Leiras¹,

Velo²,

Martín-Cora³

et al. 2010

J. Neurosci.

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Medial lemniscal activity decreases before and during movement, suggesting prethalamic modulation, but the underlying mechanisms are largely unknown. Here we studied the mechanisms underlying proprioceptive transmission at the midventral cuneate nucleus (mvCN) of anesthetized cats using standard extracellular recordings combined with electrical stimulation and microiontophoresis. Dual simultaneous recordings from mvCN and rostroventral cuneate (rvCN) proprioceptive neurons demonstrated that microstimulation through the rvCN recording electrode induced dual effects on mvCN projection cells: potentiation when both neurons had excitatory receptive fields in muscles acting at the same joint, and inhibition when rvCN and mvCN cells had receptive fields located in different joints. GABA and/or glycine consistently abolished mvCN spontaneous and sensory-evoked activity, an effect reversed by bicuculline and strychnine, respectively; and immunohistochemistry data revealed that cells possessing strychnine-sensitive glycine receptors were uniformly distributed throughout the cuneate nucleus. It was also found that proprioceptive mvCN projection cells sent ipsilateral collaterals to the nucleus reticularis gigantocellularis and the mesencephalic locomotor region, and had slower antidromic conduction speeds than cutaneous fibers from the more dorsally located cluster region.The data suggest that (1) the rvCN-mvCM network is functionally related to joints rather than to single muscles producing an overall potentiation of proprioceptive feedback from a moving forelimb joint while inhibiting, through GABAergic and glycinergic interneurons, deep muscular feedback from other forelimb joints; and (2) mvCN projection cells collateralizing to or through the ipsilateral reticular formation allow for bilateral spreading of ascending proprioceptive feedback information.

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Section: Methodsmentioning

confidence: 99%

Processing Afferent Proprioceptive Information at the Main Cuneate Nucleus of Anesthetized Cats

Leiras¹,

Velo²,

Martín-Cora³

et al. 2010

J. Neurosci.

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“…Glycinergic synapses were thought for some time to be mainly localized in the spinal cord and brainstem (for review, see [21,22]). It is now well established that glycinecontaining fibers and cell bodies and GlyRs are more widely distributed in the CNS.…”

Section: Localization Of Glycinergic Inhibitory Neurons Glycine-contmentioning

confidence: 99%

The glycinergic inhibitory synapse

Legendre¹

2001

CMLS, Cell. Mol. Life Sci.

481

474

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Glycine is one of the most important inhibitory neurotransmitters in the spinal cord and the brainstem, and glycinergic synapses have a well-established role in the regulation of locomotor behavior. Research over the last 15 years has yielded new insights on glycine neurotransmission. Glycinergic synapses are now known not to be restricted to the spinal cord and the brainstem. Presynaptic machinery for glycine release and uptake, the structure and function of postsynaptic receptors and the factors (both pre- and postsynaptic) which control the strength of glycinergic inhibition have been extensively studied. It is now established that glycinergic synapses can be excitatory in the immature brain and that some inhibitory synapses can corelease gamma-aminobutyric acid (GABA) and glycine. Moreover, the presence of glycine transporters on glial cells and the capacity of these cells to release glycine suggest that glycine may also act as a neuromodulator. Extensive molecular studies have revealed the presence of distinct subtypes of postsynaptic glycine receptors with different functional properties. Mechanisms of glycine receptors aggregation at postsynaptic sites during development are better understood and functional implications of variation in receptor number between postsynaptic sites are partly elucidated. Mutations of glycine receptor subunits have been shown to underly some human locomotor disorders, including the startle disease. Clearly, recent work on glycine receptor channels and the synapses at which they mediate inhibitory signalling in both young and adult animals necessitates an update of our vision of glycinergic inhibitory transmission.

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“…This is supported by the eVects of strychnine, the competitive antagonist of the inhibitory glycine receptor. One of the prodromal symptoms in strychnine intoxication is hyperacusis (Becker 1992). It is not known, however, whether this phenomenon is due to central or peripheral disinhibition or both.…”

Section: Glycine Receptors In Ohcsmentioning

confidence: 99%

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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Convulsants Acting at the Inhibitory Glycine Receptor

Cited by 16 publications

References 172 publications

Processing Afferent Proprioceptive Information at the Main Cuneate Nucleus of Anesthetized Cats

Processing Afferent Proprioceptive Information at the Main Cuneate Nucleus of Anesthetized Cats

The glycinergic inhibitory synapse

Expression of glycine receptors and gephyrin in the rat cochlea

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