Developmental nicotine exposure alters neurotransmission and excitability in hypoglossal motoneurons.
Hypoglossal motoneurons (XII MNs) control muscles of the mammalian tongue and are rhythmically active during breathing. Acetylcholine (ACh) modulates XII MN activity by promoting the release of glutamate from neurons that express nicotinic ACh receptors (nAChRs). Chronic nicotine exposure alters nAChRs on neurons throughout the brain, including brain stem respiratory neurons. Here we test the hypothesis that developmental nicotine exposure (DNE) reduces excitatory synaptic input to XII MNs. Voltage-clamp experiments in rhythmically active medullary slices showed that the frequency of excitatory postsynaptic currents (EPSCs) onto XII MNs from DNE animals is reduced by 61% (DNE = 1.7 ± 0.4 events/s; control = 4.4 ± 0.6 events/s; P < 0.002). We also examine the intrinsic excitability of XII MNs to test whether cells from DNE animals have altered membrane properties. Current-clamp experiments showed XII MNs from DNE animals had higher intrinsic excitability, as evaluated by measuring their response to injected current. DNE cells had high-input resistances (DNE = 131.9 ± 13.7 MΩ, control = 78.6 ± 9.7 MΩ, P < 0.008), began firing at lower current levels (DNE = 144 ± 22 pA, control = 351 ± 45 pA, P < 0.003), and exhibited higher frequency-current gain values (DNE = 0.087 ± 0.012 Hz/pA, control = 0.050 ± 0.004 Hz/pA, P < 0.02). Taken together, our data show previously unreported effects of DNE on XII MN function and may also help to explain the association between DNE and the incidence of central and obstructive apneas.
The University of Arizona, College of Medicine, Department of Physiology, P.O. Box 210093, Tucson, AZ 85721-0093, USA. pilarski@email.arizona.edu
Jason Q
JQ
Pilarski
Hilary E
HE
Wakefield
Andrew J
AJ
Fuglevand
Richard B
RB
Levine
Ralph F
RF
Fregosi
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000502:physiology*; D055592:Biophysical Phenomena; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007002:Hypoglossal Nerve / Q000187:drug effects* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D009538:Nicotine