Tonic nicotinic transmission enhances spinal <scp>GABA</scp>ergic presynaptic release and the frequency of spontaneous network activity

González-Islas, Carlos; García-Bereguiaín, Miguel Angel; O'Flaherty, Brendan M.; Wenner, Peter

doi:10.1002/dneu.22315

Cited by 13 publications

(6 citation statements)

References 54 publications

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“…In the brainstem, nAChRs are expressed postsynaptically on hypoglossal motoneurons (XIIMNs), where they evoke direct depolarization, but are also located on glutamatergic, GABAergic, and glycinergic neurons, where their role is to regulate neurotransmitter release (Bradaia & Trouslard, ; Gonzalez‐Islas et al . ; Howe et al . ).…”

Section: Introductionmentioning

confidence: 99%

Developmental plasticity of GABAergic neurotransmission to brainstem motoneurons

Wollman

Levine

Fregosi

2018

The Journal of Physiology

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Nicotinic acetylcholine receptor (nAChR) signalling regulates neuronal differentiation and synaptogenesis. Here we test the hypothesis that developmental nicotine exposure (DNE) disrupts the development of GABAergic synaptic transmission to hypoglossal motoneurons (XIIMNs). GABAergic spontaneous and miniature inhibitory postsynaptic currents (sIPSCs/mIPSCs) were recorded from XIIMNs in brainstem slices from control and DNE rat pups of either sex, 1-5 days old, at baseline and following acute stimulation of nAChRs with nicotine. At baseline, sIPSCs were less frequent and smaller in DNE cells (consistent with decreased action potential-mediated GABA release), and mIPSCs were more frequent (consistent with increased vesicular GABA release from presynaptic terminals). Acute nicotine challenge increased sIPSC frequency in both groups, though the increase was greater in DNE cells. Acute nicotine challenge did not change the frequency of mIPSCs in either group, though mIPSC amplitude increased significantly in DNE cells, but not control cells. Stimulation of postsynaptic GABA receptors with muscimol caused a significantly greater chloride current in DNE cells than in control cells. The increased quantal release of GABA, coupled with the rise in the strength of postsynaptic inhibition may be homeostatic adjustments to the decreased action-potential-mediated input from GABAergic interneurons. However, this will exaggerate synaptic inhibition under conditions where the release of GABA (e.g. hypoxia) or ACh (sleep-wake transitions) is increased. These findings reveal a mechanism that may explain why DNE is associated with deficits in the ability to respond appropriately to chemosensory stimuli or to changes in neuromodulation secondary to changes in central nervous system state.

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Section: Introductionmentioning

confidence: 99%

Developmental plasticity of GABAergic neurotransmission to brainstem motoneurons

Wollman

Levine

Fregosi

2018

The Journal of Physiology

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“…Nicotinic cholinergic signaling also plays a key role during development, including driving the expression of the chloride transporter found in mature neurons, which results in the inhibitory action of glycine (Spitzer 2010). Moreover, activation of nicotinic acetylcholine receptors (nAChRs) can modulate glycine release because of their expression at multiple locations on glycinergic neurons, including dendrites, cell body, and axon end terminals (Bradaïa and Trouslard 2002;Gonzalez-Islas et al 2016;Howe et al 2016). Many studies report that perinatal exposure to nicotine alters the morphology and normal function of neurons (Blood-Siegfried and Rende 2010;Muhammad et al 2012;Roy et al 2002), and the function of nAChRs in many brain regions (Picciotto et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Developmental nicotine exposure alters glycinergic neurotransmission to hypoglossal motoneurons in neonatal rats

Wollman

Levine

Fregosi

2018

Journal of Neurophysiology

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We tested the hypothesis that nicotine exposure in utero and after birth [developmental nicotine exposure (DNE)] disrupts development of glycinergic synaptic transmission to hypoglossal motoneurons (XIIMNs). Glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brain stem slices from 1- to 5-day-old rat pups of either sex, under baseline conditions and following stimulation of nicotinic acetylcholine (ACh) receptors with nicotine (i.e., an acute nicotine challenge). Under baseline conditions, there were no significant effects of DNE on the amplitude or frequency of either sIPSCs or mIPSCs. In addition, DNE did not alter the magnitude of the whole cell current evoked by bath application of glycine, consistent with an absence of change in postsynaptic glycine-mediated conductance. An acute nicotine challenge (bath application of 0.5 μM nicotine) increased sIPSC frequency in the DNE cells, but not control cells. In contrast, nicotine challenge did not change mIPSC frequency in either control or DNE cells. In addition, there were no significant changes in the amplitude of either sIPSCs or mIPSCs in response to nicotine challenge. The increased frequency of sIPSCs in response to an acute nicotine challenge in DNE cells reflects an enhancement of action potential-mediated input from glycinergic interneurons to hypoglossal motoneurons. This could lead to more intense inhibition of hypoglossal motoneurons in response to exogenous nicotine or endogenous ACh. The former would occur with smoking or e-cigarette use while the latter occurs with changes in sleep state and with hypercapnia. NEW & NOTEWORTHY Here we show that perinatal nicotine exposure does not impact baseline glycinergic neurotransmission to hypoglossal motoneurons but enhances glycinergic inputs to hypoglossal motoneurons in response to activation of nicotinic acetylcholine (ACh) receptors with acute nicotine. Given that ACh is the endogenous ligand for nicotinic ACh receptors, the latter reveals a potential mechanism whereby perinatal nicotine exposure alters motor function under conditions where ACh release increases, such as the transition from non-rapid-eye movement to rapid-eye movement sleep, and during hypercapnia.

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“…It has been recently reported that simply reducing GABA A R activation due to spontaneous miniature release of GABA vesicles (spontaneous GABAergic transmission) was sufficient to trigger upscaling (Garcia-Bereguiain et al, 2016). We were able to do this by taking advantage of our observation that manipulating nicotinic receptor activation altered spontaneous GABAergic release (Gonzalez-Islas et al, 2016). In this previous study, we showed that the nicotinic antagonist DHb E reduces GABA A , but not AMPA, mPSCs by ;30%.…”

Section: The Trigger For Changes In Rmp Was Distinct From the Homeostmentioning

confidence: 73%

Homeostatic Recovery of Embryonic Spinal Activity Initiated by Compensatory Changes in Resting Membrane Potential

González-Islas

García-Bereguiaín

Wenner

2020

eNeuro

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When baseline activity in a neuronal network is modified by external challenges, a set of mechanisms is prompted to homeostatically restore activity levels. These homeostatic mechanisms are thought to be profoundly important in the maturation of the network. It has been shown that blockade of either excitatory GABAergic or glutamatergic transmission in the living chick embryo transiently blocks the movements generated by spontaneous network activity (SNA) in the spinal cord. However, the embryonic movements then begin to recover by 2 h and are completely restored by 12 h of persistent receptor blockade. It remains unclear what mechanisms mediate this early recovery (first hours) after neurotransmitter blockade, or even if the same mechanisms are triggered following GABAergic and glutamatergic antagonists. Here we find two distinct mechanisms that could underlie this homeostatic recovery. First, we see a highly robust compensatory mechanism observed shortly after neurotransmitter receptor blockade. In the first 2 h of GABAergic or glutamatergic blockade in vitro, there was a clear depolarization of resting membrane potential (RMP) in both motoneurons and interneurons. These changes reduced threshold current and were observed in the continued presence of the antagonist. Therefore, it appears that fast changes in RMP represent a key fast homeostatic mechanism for the maintenance of network activity. Second, we see a less consistent compensatory change in the absolute threshold voltage in the first several hours of in vitro and in vivo neurotransmitter blockade. These mechanisms likely contribute to the homeostatic recovery of embryonic movements following neurotransmitter blockade.

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Tonic nicotinic transmission enhances spinal GABAergic presynaptic release and the frequency of spontaneous network activity

Cited by 13 publications

References 54 publications

Developmental plasticity of GABAergic neurotransmission to brainstem motoneurons

Developmental plasticity of GABAergic neurotransmission to brainstem motoneurons

Developmental nicotine exposure alters glycinergic neurotransmission to hypoglossal motoneurons in neonatal rats

Homeostatic Recovery of Embryonic Spinal Activity Initiated by Compensatory Changes in Resting Membrane Potential

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