Development of synaptic transmission to respiratory motoneurons

Abstract

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. Further, the relative role of each receptor type in inspiratory-phase motoneuron depolarization is dependent on the type of preparation used (in vitro versus in vivo; neonatal versus adult). Respiratory motoneurons receive both glycinergic and GABAergic inhibitory synaptic inputs. During inspiration phrenic and HMs receive concurrent excitatory and inhibitory synaptic inputs. During postnatal development in HMs GABAergic and glycinergic synaptic inputs have slow kinetics and are depolarizing and with postnatal development they become faster and hyperpolarizing. Additionally shunting inhibition may play an important role in synaptic processing by respiratory motoneurons.

KCC2-mediated regulation of respiration-related rhythmic activity during postnatal development in mouse medulla oblongata

“…In addition, Sebe et al (2006) reported that GABAergic and glycinergic transmission are required to generate robust synchronous burst oscillations of neurons in 12 N over postnatal development. This result and our data suggest that decreasing of [Cl À ] i during development might increase the frequency of burst oscillations of neurons in 12 N. Since this phenomenon cause that the time course of inhibitory synaptic transmission speeds up with postnatal development (Berger, 2011), it means that the duration time of RRA could be decreased. Therefore, neurons in 12 N might prepare for the next burst activity very quickly but it is still unclear that inhibitory GABAergic responses can increase the RRA frequency.…”

Respiratory muscles and motoneurons

“…A consideration of the major gaps in our understanding of tongue muscle and hypoglossal motoneuron anatomy and physiology is considered next (Fregosi, 2011), followed by a detailed discussion of the respiration-related and volitional control of genioglossus muscle motor units (Bailey, 2011). The issue concludes with a consideration of how synaptic transmission in the hypoglossal motoneuron pool develops (Berger, 2011), as well as how excitotoxic and oxidative stress alters the function of developing hypoglossal motoneurons (Cifra et al, 2011). …”

Pre- and postsynaptic modulations of hypoglossal motoneurons by α-adrenoceptor activation in wild-type and Mecp2−/Y mice

“…The main source of GABAergic and glycinergic inhibitory inputs to the HNs derives from the nucleus of Roller (2, 62), which affect the HNs via activation of postsynaptic GABA A and glycine receptors (2, 5, 52, 62). These inhibitory synaptic inputs control hypoglossal responses to other synaptic inputs, shape the temporospatial pattern of neuronal activity during reflex and rhythmic behaviors, and contribute to the generation of inspiratory motoneuronal synchrony (5,49,53).The strength of these synaptic inhibitions of HNs is modulated by brainstem norepinephrine (NE) systems by ␣-adrenoceptors (18). The ␣-adrenoceptors contain two main types including ␣ 1 and ␣ 2 , each comprising at least three subtypes (13, 42).…”

“…The HNs receive excitatory and inhibitory synaptic inputs (1,7,19,47,51,69). The main source of GABAergic and glycinergic inhibitory inputs to the HNs derives from the nucleus of Roller (2,62), which affect the HNs via activation of postsynaptic GABA A and glycine receptors (2,5,52,62). These inhibitory synaptic inputs control hypoglossal responses to other synaptic inputs, shape the temporospatial pattern of neuronal activity during reflex and rhythmic behaviors, and contribute to the generation of inspiratory motoneuronal synchrony (5,49,53).…”

“…Such defects should have profound impact on the inhibitory synaptic transmissions, especially in the motorneuronal system including HNs, as motor defects are characteristic in people with RTT (11,22,53). Under the condition of GABAergic defects, the motoneuronal system may rely more on glycinergic system, because the glycinergic system plays an important role in inhibitory synaptic transmission in motoneurons (5,59,67), suggesting the necessity to know how the Mecp2 disruption affects the glycinergic system. Therefore, we performed whole cell patch-clamp studies to determine what happens to the glycinergic synaptic currents in Mecp2-null mice and how the modulation of glycinergic synaptic transmission by ␣ 1 -adrenoceptor is affected.…”