Glycinergic Transmission Shaped by the Corelease of GABA in a Mammalian Auditory Synapse

Lu, Tao; Rubio, María E.; Trussell, Laurence O.

doi:10.1016/j.neuron.2007.12.010

Cited by 114 publications

(125 citation statements)

References 78 publications

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“…However, the effective period of glycinergic inhibition determined in MSO brain slice experiments using multiple inputs was Ͻ1 ms (Grothe and Sanes, 1994). Recently, it was shown in MNTB membrane patches that the kinetics of glycinergic inhibition is accelerated by the corelease of GABA (Lu et al, 2008). Hence, it is currently unclear how fast inhibition can act in vivo and how fast it would have to be to make our scenario feasible [note that Brand et al (2002) only aimed for proof of principle, not for assessing the kinetics required].…”

Section: Pharmacologymentioning

confidence: 99%

Interaural Time Difference Processing in the Mammalian Medial Superior Olive: The Role of Glycinergic Inhibition

Pecka

Brand²,

Behrend³

et al. 2008

Journal of Neuroscience

212

268

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The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.

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Section: Pharmacologymentioning

confidence: 99%

Interaural Time Difference Processing in the Mammalian Medial Superior Olive: The Role of Glycinergic Inhibition

Pecka

Brand²,

Behrend³

et al. 2008

Journal of Neuroscience

212

268

View full text Add to dashboard Cite

show abstract

“…This variability may be underestimated because spontaneous activity samples multiple presynaptic partners, potentially with different IPSC kinetics. Indeed, synaptically released GABA is known to generate fast-decaying glycinergic IPSCs (Lu et al, 2008) caused by the low-affinity binding and rapid unbinding of GABA at the agonist site on GlyRs. If the variability of kinetics is determined by the ratio of GABA and glycine released by GoCs, pIPSC and uIPSC kinetics should vary independently.…”

Section: Ipsc Decay Kinetics and Gaba/glycinergic Inhibitory Profilementioning

confidence: 99%

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Rousseau¹,

Dugué²,

Dumoulin³

et al. 2012

J. Neurosci.

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Inhibitory synapses display a great diversity through varying combinations of presynaptic GABA and glycine release and postsynaptic expression of GABA and glycine receptor subtypes. We hypothesized that increased flexibility offered by this dual transmitter system might serve to tune the inhibitory phenotype to the properties of afferent excitatory synaptic inputs in individual cells. Vestibulocerebellar unipolar brush cells (UBC) receive a single glutamatergic synapse from a mossy fiber (MF), which makes them an ideal model to study excitatory-inhibitory interactions. We examined the functional phenotypes of mixed inhibitory synapses formed by Golgi interneurons onto UBCs in rat slices. We show that glycinergic IPSCs are present in all cells. An additional GABAergic component of large amplitude is only detected in a subpopulation of UBCs. This GABAergic phenotype is strictly anti-correlated with the expression of type II, but not type I, metabotropic glutamate receptors (mGluRs) at the MF synapse. Immunohistochemical stainings and agonist applications show that global UBC expression of glycine and GABA A receptors matches the pharmacological profile of IPSCs. Paired recordings of Golgi cells and UBCs confirm the postsynaptic origin of the inhibitory phenotype, including the slow kinetics of glycinergic components. These results strongly suggest the presence of a functional coregulation of excitatory and inhibitory phenotypes at the single-cell level. We propose that slow glycinergic IPSCs may provide an inhibitory tone, setting the gain of the MF to UBC relay, whereas large and fast GABAergic IPSCs may in addition control spike timing in mGluRII-negative UBCs.

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“…GABA and glycine probably act on different receptors at the same neuron, since their effects were reversed by BiCu and strychnine, respectively. Whether in physiological conditions both neurotransmitters are coreleased by the same or different terminals is unknown, but cotransmission is common in the CNS (Burnstock, 2004); GABA and glycine colocalize in the rat's dorsal column nuclei (Popratiloff et al, 1996), and their functional corelease has been reported in other regions of the brainstem (O'Brien and Berger, 1999;Russier et al, 2002;Awatramani et al, 2005;Lu et al, 2008). Corelease and/or simultaneity of action on postsynaptic receptors will increase the efficiency of synaptic transmission.…”

Section: Gaba and Glycine Constrained Mvcn Responses To A Single Artimentioning

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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Glycinergic Transmission Shaped by the Corelease of GABA in a Mammalian Auditory Synapse

Cited by 114 publications

References 78 publications

Interaural Time Difference Processing in the Mammalian Medial Superior Olive: The Role of Glycinergic Inhibition

Interaural Time Difference Processing in the Mammalian Medial Superior Olive: The Role of Glycinergic Inhibition

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

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

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