Development of synaptic transmission to respiratory motoneurons.

Respiratory motoneurons provide the exclusive drive to respiratory muscles and therefore are a key relay between brainstem neural circuits that generate respiratory rhythm and respiratory muscles that control moment of gases into and out of the airways and lungs. This review is focused on postnatal development of fast ionotropic synaptic transmission to respiratory motoneurons, with a focus on hypoglossal motoneurons (HMs). Glutamatergic synaptic transmission to HMs involves activation of both non-NMDA and NMDA receptors and during the postnatal period co-activation of these receptors located at the same synapse may occur.

Spike-firing resonance in hypoglossal motoneurons.

During an inspiration the output of hypoglossal (XII) motoneurons (HMs) in vitro is characterized by synchronous oscillatory firing in the 20- to 40-Hz range. To maintain synchronicity it is important that the cells fire with high reliability and precision. It is not known whether the intrinsic properties of HMs are tuned to maintain synchronicity when stimulated with time-varying inputs.

Developmental effects of ketamine on inspiratory hypoglossal nerve activity studied in vivo and in vitro.

The effects of the anesthetic ketamine on properties of inspiratory bursts (I-bursts) in mouse hypoglossal nerve activity were studied in vivo and in vitro. In urethane anesthetized mice we observed rhythmic I-phase activity in only one of eight pups at P9 days. In contrast in older mice rhythmic I-phase hypoglossal activity was almost always observed.

Inhibitory synaptic transmission governs inspiratory motoneuron synchronization.

Neurons within the intact respiratory network produce bursts of action potentials that cause inspiration or expiration. Within inspiratory bursts, activity is synchronized on a shorter timescale to generate clusters of action potentials that occur in a set frequency range and are called synchronous oscillations. We investigated how GABA and glycine modulate synchronous oscillations and respiratory rhythm during postnatal development.

GABA(B) modulation of GABA(A) and glycine receptor-mediated synaptic currents in hypoglossal motoneurons.

We studied the effects of GABA(B) receptor activation on either glycine or GABA(A) receptor-mediated synaptic transmission to hypoglossal motoneurons (HMs, P8-13) using a rat brainstem slice preparation. Activation of GABA(B) receptors with baclofen, a GABA(B) receptor agonist, inhibited the amplitude of evoked glycine and GABA(A) receptor-mediated inhibitory postsynaptic currents. Additionally, with blockade of postsynaptic GABA(B) receptors baclofen decreased the frequency of both glycine and GABA(A) receptor-mediated spontaneous miniature inhibitory postsynaptic currents (mIPSCs), indicating a presynaptic site of action.

Blockade of glycine transporter-1 (GLYT-1) potentiates NMDA receptor-mediated synaptic transmission in hypoglossal motorneurons.

NMDA receptor (NMDAR)-mediated spontaneous miniature excitatory postsynaptic currents (mEPSCs) are potentiated by exogenously applied glycine. In this study, we have investigated the effect of blocking glycine uptake on NMDAR-mediated responses from hypoglossal motorneurons (HMs) of rats. We have used N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-propyl]sarcosine (NFPS; 500 nM), an antagonist of glycine transporter-1 (GLYT1), to study the effect of blocking endogenous glycine uptake on NMDAR-mediated synaptic transmission.

Mechanisms for the modulation of native glycine receptor channels by ethanol.

Previously, we showed that ethanol increases synaptic glycine currents, an effect that depends on ethanol concentration and developmental age of the preparation. Glycine receptor (GlyR) subunits undergo a shift from alpha2/beta to alpha1/beta from neonate to juvenile ages, with synaptic glycine currents from neonate hypoglossal motoneurons (HMs) being less sensitive to ethanol than those from juvenile HMs. Here we investigate whether these dose and developmental effects are also present in excised membrane patches containing GlyRs and if ethanol changes response kinetics.

Differential effects of ethanol on GABA(A) and glycine receptor-mediated synaptic currents in brain stem motoneurons.

Ethanol potentiates glycinergic synaptic transmission to hypoglossal motoneurons (HMs). This effect on glycinergic transmission changes with postnatal development in that juvenile HMs (P9-13) are more sensitive to ethanol than neonate HMs (P1-3). We have now extended our previous study to investigate ethanol modulation of synaptic GABA(A) receptors (GABA(A)Rs), because both GABA and glycine mediate inhibitory synaptic transmission to brain stem motoneurons.

Activation of 5HT1B receptors inhibits glycinergic synaptic inputs to mammalian motoneurons during postnatal development.

We investigated whether 5-HT(1B) receptor-mediated inhibition of evoked glycinergic inhibitory postsynaptic currents (eIPSCs) in hypoglossal motoneurons (HMs) changed postnatally. In HMs from postnatal days 2-3 (P2-3, neonate) and P10-11 (juvenile) rats bath application of 5-HT (10 microM) caused a not significantly different large reduction in eIPSC amplitude to 35.0+/-22.