Serotoninergic control of glycinergic inhibitory postsynaptic currents in rat hypoglossal motoneurons

Engelhardt, John Kerch; Silveira, Valentina; Morales, Francisco R.; Pose, I.; Chase, Michael H.

doi:10.1016/j.brainres.2010.05.009

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…Serotonin (5‐HT) is such a candidate known to affect the respiratory network (Hilaire & Duron, 1999). A direct modulation of evoked glycinergic IPSCs has recently been reported in HMs (Engelhardt et al . 2010).…”

Section: Discussionmentioning

confidence: 79%

“…Serotonin (5-HT) is such a candidate known to affect the respiratory network (Hilaire & Duron, 1999). A direct modulation of evoked glycinergic IPSCs has recently been reported in HMs (Engelhardt et al 2010). Significantly, the expressions of several serotonergic receptor subunits (including 5-HT 1A R, 5-HT 1B R and 5-HT 2A R) as well as serotonin transporters were found to be highly expressed in multiple brainstem respiratory nuclei, including the hypoglossal nucleus, from P0 to P11, but their expressions precipitously dropped at P12 (Liu & Wong-Riley, 2010a,b).…”

Section: Excitatory-inhibitory Imbalance During the Critical Periodmentioning

confidence: 99%

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Excitatory–inhibitory imbalance in hypoglossal neurons during the critical period of postnatal development in the rat

Gao

Liu

et al. 2011

The Journal of Physiology

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Non-technical summary Previously, our laboratory has reported that within a narrow window toward the end of the second postnatal week in a rat's life, many sudden neurochemical and functional changes occurred that rendered the animal less responsive to decreased oxygen supply. The present study extends these findings to the recordings of single nerve cells and documents that, during this critical period of normal postnatal respiratory network development, the responses to excitation are significantly reduced and those to inhibition are significantly enhanced. Thus, the system is under greater inhibitory influence at this time. These findings may have significant implication for understanding sudden infant death syndrome, whose victims are seemingly normal infants with no known pathologies. The peak incidence of SIDS is not at birth, but between the second and fourth months after birth, a theoretical critical period of postnatal respiratory development.Abstract Hypoglossal motoneurons (HMs) innervate tongue muscles and are critical in maintaining patency of the upper airway during respiration. Abnormalities in HMs have been implicated in sudden infant death syndrome (SIDS) and obstructive sleep apnoea. Previously, we found a critical period in respiratory network development in rats around postnatal day (P) 12-13, when abrupt neurochemical, metabolic and physiological changes occurred. To test our hypothesis that an imbalance between inhibitory and excitatory synaptic transmission exists during the critical period, whole-cell patch-clamp recordings of HMs were done in brainstem slices of rats daily from P0 to P16. The results indicated that: (1) the amplitude and charge transfer of miniature excitatory postsynaptic currents (mEPSCs) were significantly reduced at P12-13; (2) the amplitude, mean frequency and charge transfer of miniature inhibitory postsynaptic currents (mIPSCs) were significantly increased at P12-13; (3) the kinetics (rise time and decay time) of both mEPSCs and mIPSCs accelerated with age; (4) the amplitude and frequency of spontaneous EPSCs were significantly reduced at P12-13, whereas those of spontaneous IPSCs were significantly increased at P12-13; and (5) both glycine and GABA contributed to mIPSCs. However, GABAergic currents fluctuated within a narrow range during the first three postnatal weeks, whereas glycinergic ones exhibited age-dependent changes comparable to those of total mIPSCs, indicating a reversal in dominance from GABA to glycine with development. Thus, our results provide strong electrophysiological evidence for an excitatory-inhibitory imbalance in HMs during the critical period of postnatal development in rats that may have significant implications for SIDS. Abbreviations HMs, hypoglossal motoneurons; mEPSC, miniature excitatory postsynaptic current; mIPSC, miniature inhibitory postsynaptic current; sEPSC, spontaneous excitatory postsynaptic current; SIDS, sudden infant death syndrome; sIPSC, spontaneous inhibitory postsynaptic current.

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Section: Discussionmentioning

confidence: 79%

Section: Excitatory-inhibitory Imbalance During the Critical Periodmentioning

confidence: 99%

Excitatory–inhibitory imbalance in hypoglossal neurons during the critical period of postnatal development in the rat

Gao

Liu

et al. 2011

The Journal of Physiology

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“…In contrast, GABA B receptors couple to Ca 2+ and K + channels via G proteins and second messengers (Bowery, 1989 ). Serotonergic inputs could also potentially modulate glycinergic inhibitory transmission, but there is currently little data on the effects of serotonin on glycinergic inhibition in the IC or other brain areas (Engelhardt et al, 2010 ). For this reason, we will focus on serotonergic modulation of GABAergic transmission by describing (1) the anatomical association between the serotonergic and GABAergic systems, and (2) the modulation of GABAergic transmission by serotonin.…”

Section: Serotonin Receptor Types Define Parallel Pathways For Regulamentioning

confidence: 99%

From behavioral context to receptors: serotonergic modulatory pathways in the IC

Hurley¹,

Sullivan²

2012

Front. Neural Circuits

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In addition to ascending, descending, and lateral auditory projections, inputs extrinsic to the auditory system also influence neural processing in the inferior colliculus (IC). These types of inputs often have an important role in signaling salient factors such as behavioral context or internal state. One route for such extrinsic information is through centralized neuromodulatory networks like the serotonergic system. Serotonergic inputs to the IC originate from centralized raphe nuclei, release serotonin in the IC, and activate serotonin receptors expressed by auditory neurons. Different types of serotonin receptors act as parallel pathways regulating specific features of circuitry within the IC. This results from variation in subcellular localizations and effector pathways of different receptors, which consequently influence auditory responses in distinct ways. Serotonin receptors may regulate GABAergic inhibition, influence response gain, alter spike timing, or have effects that are dependent on the level of activity. Serotonin receptor types additionally interact in nonadditive ways to produce distinct combinatorial effects. This array of effects of serotonin is likely to depend on behavioral context, since the levels of serotonin in the IC transiently increase during behavioral events including stressful situations and social interaction. These studies support a broad model of serotonin receptors as a link between behavioral context and reconfiguration of circuitry in the IC, and the resulting possibility that plasticity at the level of specific receptor types could alter the relationship between context and circuit function.

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“…Serotonergic neurons in the central nervous system could impinge on many synapses to modulate their excitability by both pre‐ and post‐synaptic mechanisms (Filip & Bader, 2009). Recent studies reported that serotonin reduced the glycinergic inhibitory postsynaptic currents in rat hypoglossal motoneurons (Engelhardt et al. , 2010).…”

Section: Discussionmentioning

confidence: 99%

Raphe pallidus modulates Bötzinger complex-induced inhibition of the phrenic nerve activity in rats

Wang

et al. 2011

European Journal of Neuroscience

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The raphe pallidus (RPa) and Bötzinger complex (BötC) represent two important nuclei which project to spinal phrenic motor neurons. Stimulation of the RPa produces facilitative effects on respiratory activity, whereas stimulation of the BötC induces inhibitory effects on respiratory activity. In the present study, we examined the modulatory effects of serotonergic (5-hydroxytryptamine, 5-HT) RPa neurons on the inhibitory response of the phrenic nerve activity elicited from the BötC in rats. Experiments were performed on spontaneously breathing, urethane-anesthetized adult rats. Either high-frequency stimulation or glutamatergic chemical activation of the RPa region significantly attenuated the BötC-induced inhibition of the phrenic nerve. This attenuation showed a post-stimulation time and intensity dependency. Pharmacological experiments showed that intravenous injection of methysergide, a broad-spectrum antagonist of 5-HT receptors, markedly reduced the respiratory facilitation induced by electrical stimulation of the RPa. Furthermore, microinjections of methysergide into the cerebrospinal fluid around the phrenic motor nucleus (PMN) region at spinal cord segments C4 and C5 significantly decreased the RPa-related attenuation effects on BötC-evoked inhibition of phrenic nerve discharge. These results suggest that RPa serotonergic neurons could modulate the inhibition of phrenic nerve activity induced by BötC. Moreover, as the relevant 5-HT receptors for RPa's modulatory effects are located in the cervical spinal cord, 5-HT may, in part, function as a modulator to suppress the BötC neuronal activity via direct RPa-PMN and BötC-PMN convergent projection pathways to phrenic motoneurons.

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Serotoninergic control of glycinergic inhibitory postsynaptic currents in rat hypoglossal motoneurons

Cited by 7 publications

References 31 publications

Excitatory–inhibitory imbalance in hypoglossal neurons during the critical period of postnatal development in the rat

Excitatory–inhibitory imbalance in hypoglossal neurons during the critical period of postnatal development in the rat

From behavioral context to receptors: serotonergic modulatory pathways in the IC

Raphe pallidus modulates Bötzinger complex-induced inhibition of the phrenic nerve activity in rats

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