Inhibitory Synaptic Transmission Differs in Mouse Type A and B Medial Vestibular Nucleus Neurons In Vitro (original) (raw)
Related papers
2000
The principal cells of the chick tangential nucleus are vestibular nucleus neurons participating in the vestibular reflexes. In 16-day embryos, the application of glutamate receptor antagonists abolished the postsynaptic responses generated on vestibular-nerve stimulation, but spontaneous synaptic activity was largely unaffected. Here, spontaneous synaptic activity was characterized in principal cells from brain slices at E16 using whole cell voltage-clamp recordings. With KCl electrodes, the frequency of spontaneous inward currents was 3.1 Hz at Ϫ60 mV, and the reversal potential was ϩ4 mV. Cs-gluconate pipette solution allowed the discrimination of glycine/GABA A versus glutamate receptor-mediated events according to their different reversal potentials. The ratio for spontaneous excitatory to inhibitory events was about 1:4. Seventy-four percent of the outward events were GABA A , whereas 26% were glycine receptor-mediated events. Both pre-and postsynaptic GABA B receptor effects were shown, with presynaptic GABA B receptors inhibiting 40% of spontaneous excitatory postsynaptic currents (sEPSCs) and 53% of spontaneous inhibitory postsynaptic currents (sIPSCs). With TTX, the frequency decreased ϳ50% for EPSCs and 23% for IPSCs. These data indicate that the spontaneous synaptic activity recorded in the principal cells at E16 is primarily inhibitory, action potential-independent, and based on the activation of GABA A receptors that can be modulated by presynaptic GABA B receptors.
Molecular Pain, 2009
Background: Neurons in superficial (SDH) and deep (DDH) laminae of the spinal cord dorsal horn receive sensory information from skin, muscle, joints and viscera. In both regions, glycine-(GlyR) and GABA A -receptors (GABA A Rs) contribute to fast synaptic inhibition. For rat, several types of GABA A R coexist in the two regions and each receptor type provides different contributions to inhibitory tone. Recent work in mouse has discovered an additional type of GlyR, (containing alpha 3 subunits) in the SDH. The contribution of differing forms of the GlyR to sensory processing in SDH and DDH is not understood.
Attenuated glycine receptor function reduces excitability of mouse medial vestibular nucleus neurons
Neuroscience, 2010
Spontaneous activity in medial vestibular nucleus (MVN) neurons is modulated by synaptic inputs. These inputs are crucial for maintaining gaze and posture and contribute to vestibular compensation after lesions of peripheral vestibular organs. We investigated how chronically attenuated glycinergic input affects excitability of MVN neurons. To this end we used three mouse strains (spastic, spasmodic, and oscillator), with well-characterized naturally occurring mutations in the inhibitory glycine receptor (GlyR). First, using wholecell patch-clamp recordings, we demonstrated that the amplitude of the response to rapidly applied glycine was dramatically reduced by 25 to 90% in MVN neurons from mutant mice. We next determined how reduced GlyR function affected MVN neuron output. Neurons were classified using two schemas: (1) the shape of their action potential afterhyperpolarization (AHP); and (2) responses to hyperpolarizing current injection. In the first schema, neurons were classified as types A, B and C. The prevalence of type C neurons in the mutant strains was significantly increased. In the second schema, the proportion of neurons lacking post inhibitory rebound firing (PRF-deficient) was increased. In both schemas an increase in AHP amplitude was a common feature of the augmented neuron group (type C, PRF-deficient) in the mutant strains. We suggest increased AHP amplitude reduces overall excitability in the MVN and thus maintains network function in an environment of reduced glycinergic input.
European Journal of Neuroscience, 2007
Inhibitory postsynaptic currents (IPSCs) of the thalamic reticular (RT) nucleus are dramatically slower than in the neighboring ventrobasal (VB) neurons. It has been suggested that a3-subunit-containing receptors underlie slow IPSCs in RT neurons, while rapid synaptic currents in the VB nucleus are due to c-aminobutyric acid A receptors (GABA A Rs), including the a1-subunit. In our recent study Eur. J. Neurosci., 25, 2726J. Neurosci., 25, -2740 we have found that profound differences in kinetics of currents mediated by a3b2c2 and a1b2c3 receptors resulted from distinct binding and desensitization properties. However, a direct comparison between kinetics of neuronal GABA A Rs from RT and VB neurons and a3-and a1-subunit-containing receptors has not been made. For this purpose, current responses to ultrafast GABA applications were recorded from patches excised from neurons in VB and RT areas. Deactivation kinetics determined for RT and VB neurons closely resembled that in currents mediated by a3b2c2 and a1b2c2 receptors. In RT neurons, currents elicited by non-saturating [GABA] had a remarkably slow onset, a hallmark of a3subunit-containing receptors. In VB and RT neurons, single-channel currents elicited by brief GABA pulses had similar characteristics to those of a1b2c2 and a3b2c2 receptors. However, in stationary conditions, similarity between single-channel currents in neurons and respective recombinant receptors was less apparent. We propose that the non-stationary kinetics of GABAergic currents in VB and RT nuclei mimic that of currents mediated by a1-and a3-subunit-containing receptors. The dissimilarity between stationary kinetics of neuronal and recombinant receptors probably reflects differences between GABA A Rs mediating phasic and tonic currents in these neurons.
Eur J Neurosci, 2007
Inhibitory postsynaptic currents (IPSCs) of the thalamic reticular (RT) nucleus are dramatically slower than in the neighboring ventrobasal (VB) neurons. It has been suggested that a3-subunit-containing receptors underlie slow IPSCs in RT neurons, while rapid synaptic currents in the VB nucleus are due to c-aminobutyric acid A receptors (GABA A Rs), including the a1-subunit. In our recent study [Barberis et al. (2007) Eur. J. Neurosci., 25, 2726-2740] we have found that profound differences in kinetics of currents mediated by a3b2c2 and a1b2c3 receptors resulted from distinct binding and desensitization properties. However, a direct comparison between kinetics of neuronal GABA A Rs from RT and VB neurons and a3-and a1-subunit-containing receptors has not been made. For this purpose, current responses to ultrafast GABA applications were recorded from patches excised from neurons in VB and RT areas. Deactivation kinetics determined for RT and VB neurons closely resembled that in currents mediated by a3b2c2 and a1b2c2 receptors. In RT neurons, currents elicited by non-saturating [GABA] had a remarkably slow onset, a hallmark of a3subunit-containing receptors. In VB and RT neurons, single-channel currents elicited by brief GABA pulses had similar characteristics to those of a1b2c2 and a3b2c2 receptors. However, in stationary conditions, similarity between single-channel currents in neurons and respective recombinant receptors was less apparent. We propose that the non-stationary kinetics of GABAergic currents in VB and RT nuclei mimic that of currents mediated by a1-and a3-subunit-containing receptors. The dissimilarity between stationary kinetics of neuronal and recombinant receptors probably reflects differences between GABA A Rs mediating phasic and tonic currents in these neurons.
Neuroscience, 1998
In rat brainstem slices, we investigated the possible role of metabotropic glutamate receptors in modulating the synaptic transmission within the medial vestibular nuclei, under basal and plasticity inducing conditions. We analysed the effect of the metabotropic glutamate receptor antagonist (R,S)-methyl-4-carboxyphenylglycine on the amplitude of the field potentials and latency of unitary potentials evoked in the ventral portion of the medial vestibular nuclei by primary vestibular afferent stimulation, and on the induction and maintenance of long-term potentiation, after high-frequency stimulation. Two effects were observed, consisting of a slight increase of the field potentials and reduction of unit latency during the drug infusion, and a further long-lasting development of these modifications after the drug wash-out. The long-term effect depended on N-methyl--aspartate receptor activation, as ,-2amino-5-phosphonopentanoic acid prevented its development. We suggest that (R,S)-methyl-4carboxyphenylglycine enhances the vestibular responses and induces N-methyl--aspartate-dependent long-term potentiation by increasing glutamate release, through the block of presynaptic metabotropic glutamate receptors which actively inhibit it. The block of these receptors was indirectly supported by the fact that the agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid reduced the vestibular responses and blocked the induction of long-term potentiation by high-frequency stimulation. The simultaneous block of metabotropic glutamate receptors facilitating synaptic plasticity, impedes the full expression of the long-term effect throughout the (R,S)-methyl-4-carboxyphenylglycine infusion. The involvement of such a facilitatory mechanism in the potentiation is supported by its reversible reduction following a second (R,S)-methyl-4-carboxyphenylglycine infusion. The drug also reduced the expression of potentiation induced by high-frequency stimulation. Conversely the electrical long-term potentiation was still induced, but it was occluded by the previous drug potentiation. We conclude that metabotropic glutamate receptors play a dual functional role in the medial vestibular nuclei, consisting in the inhibition of glutamate release under basal conditions, and the facilitation of N-methyl--aspartate-dependent plasticity phenomena. 1998 IBRO. Published by Elsevier Science Ltd.
European Journal of Neuroscience, 2003
The mammalian superior colliculus (SC) is reported to contain g-aminobutyric acid (GABA) C receptors (GABA C Rs) at high concentration. However, their role in GABAergic synaptic transmission is not yet known. The aim of the present study was: (i) to clarify whether GABA C Rs are activated by endogenous GABA; and (ii), to determine whether GABA C Rs play a role in inhibitory synaptic transmission. Experiments were performed on acute horizontal slices from the postnatal rat SC or on collicular neurons in dissociated cell culture. In both preparations, bicuculline-resistant current responses to exogenous GABA and currents elicited by cis-4aminocrotonic acid (CACA) were blocked by (1,2,5,6-tetrahydropyridine-4-yl) methylphosphinic acid (TPMPA), a GABA C R antagonist. The CACA-induced currents exhibited a linear current-voltage relationship and reversed at the Cl À equilibrium potential. These results indicate that functional GABA C Rs are present in the somato-dendritic membrane of collicular neurons. Miniature inhibitory postsynaptic currents (mIPSCs) were recorded using the whole-cell patch clamp technique. TPMPA signi®cantly decreased mIPSC amplitudes in slices, but not in cultured neurons. As TPMPA decreased also the coef®cient of variation of mIPSCs, we suggest that somatodendritic GABA C Rs are located extrasynaptically but can be involved in the generation of IPSCs if GABA diffusion is constrained. In cultures, individual connections were activated by focal electrical stimulation of single neurons, and evoked inhibitory postsynaptic currents (eIPSCs) were recorded. Paired-pulse stimulation revealed that TPMPA signi®cantly decreased the paired-pulse ratio at short (50 ms) interstimulus intervals, and this effect was inversely dependent on the amplitude of the ®rst eIPSC. We conclude that presynaptic GABA C Rs are activated by endogenous GABA and can alleviate the short-term depression resulting from a preceding episode of GABA release. Thus, in GABAergic synapses of the SC GABA C Rs are involved in pre-and postsynaptic functions and may therefore contribute to the activity-dependent adjustment of GABAergic inhibition.