Autoradiographic localization of neurotransmitter binding sites in the hypoglossal and motor trigeminal nuclei of the rat

Abstract

The hypoglossal and motor trigeminal nuclei contain somatic motoneurons innervating the tongue, jaw, and palate. These two cranial motor nuclei are myotopically organized and contain neurotransmitter binding sites for thyrotropin-releasing hormone, substance P, and serotonin. Quantitative autoradiography was used to localize thyrotropin-releasing hormone, substance P, and serotonin-1A and serotonin-1B binding sites in the hypoglossal and motor trigeminal nuclei and to relate the relative distributions of these binding sites to the myotopic organizations of the two nuclei. In the hypoglossal nucleus, high-to-moderate concentrations of all four binding sites were present in the dorsal and ventromedial subnuclei, whereas low concentrations were noted in the ventrolateral subnucleus. In the motor trigeminal nucleus, high concentrations of serotonin-1B, moderate densities of thyrotropin-releasing hormone, and low levels of substance P and serotonin-1A binding sites were present in both the ventromedial and dorsolateral subnuclei. These observations demonstrate that neurotransmitter binding sites in the hypoglossal and motor trigeminal nuclei are heterogeneously localized and that their distributions correspond to the previously described myotopic organizations of each nucleus.

Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro

“…SP interacts with NK1 receptors, NKA with NK2 receptors and NKB with NK3 receptors (Rekling et al 2000). Our focus on NK1 receptors was based on extensive anatomical and electrophysiological evidence that: (i) of the three neurokinin receptors, NK1 receptors are predominantly expressed in spinal motoneurons (Dam et al 1990a(Dam et al ,b, 1993Yashpal et al 1990;Beresford et al 1992;Nakaya et al 1994;Ding et al 1996;Manaker & Zucchi, 1998); (ii) that the postsynaptic actions of SP are mimicked by NK1 agonists (Fisher et al 1994;Lepre et al 1996);and (iii) that the minor effects of NKA and NKB receptor stimulation are largely blocked by TTX, suggesting a presynaptic location (Matsuto et al 1984;Fisher et al 1994;Ptak et al 2000). Antagonism of NK1 receptors has variable effects on SP or NK1 agonistinduced depolarization in neonatal tissue.…”

“…Recent data on phrenic MNs suggest that the effects of SP differ between endogenous inspiratory inputs and somally injected inputs (Ptak et al 2000). In addition, the high expression of NK1 receptors in spinal (particularly phrenic) MN pools relative to moderate or low expression in XII, facial and trigeminal motoneuron pools (Charlton & Helke, 1985;Yashpal et al 1990;Nakaya et al 1994;Manaker & Zucchi, 1998) suggests that actions may differ between motoneuron pools. Given the hypothesis that a mismatch of activity in upper airway and inspiratory pump muscles contributes to apnoea (Hudgel & Harasick, 1990), there is considerable interest in understanding the basis of this differential excitability.…”

“…In XII MNs, NK1 receptor expression is only moderate relative to the high levels observed in spinal, particularly phrenic, motoneurons (Charlton & Helke, 1985;Yashpal et al 1990;Nakaya et al 1994;Manaker & Zucchi, 1998). However, potentiation of inspiratory output and MN excitability by the NK1-selective agonist [SAR 9 ,Met (O 2 ) 11 ]-SP and the sensitivity of these actions to GR82334 confirm that NK1 receptors increase XII MN excitability to exogenous inputs and endogenous inspiratory drive.…”

“…That these effects are physiological rather than pharmacological is supported by: (i) the presence of SPcontaining terminals in the XII nucleus (Connaughton et al 1986;Gatti et al 1999) (Fig. 14); (ii) EM evidence for synaptic interactions between XII MNs and SPcontaining terminals (Gatti et al 1996); (iii) receptor immunoreactvity (Nakaya et al 1994) and binding sites (Manaker & Zucchi, 1998) in the XII nucleus; (iv) the presence of SP in raphe neurons that innervate the XII nucleus (Henry & Manaker, 1998); and (v) our observation that GR82334 inhibits endogenous inspiratory output and generates an outward current in individual XII MNs.…”

Synaptic Control of Motoneuronal Excitability

“…The expression of NK 1 receptors is not uniform among motoneuronal pools, however, implying that effects of substance P may vary depending on the particular motoneuronal pool. For example, some motoneuronal populations express very high levels, e.g., phrenic, pudendal motoneurons, whereas others express moderate, e.g., hypoglossal motoneurons, or only very low levels of NK 1 receptor, e.g., facial, trigeminal motoneurons (210,791,892,1405). The NK 2 receptor is preferentially located in the periphery with only low levels of binding sites in the CNS, whereas the NK 3 receptor has a widespread CNS distribution; neither NK 2 or NK 3 receptors, however, are prominent in motor nuclei (272,293,1149,1405).…”