Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons

Abstract

Developmental nicotine exposure (DNE) is associated with increased risk of cardiorespiratory, intellectual, and behavioral abnormalities in neonates, and is a risk factor for apnea of prematurity, altered arousal responses and Sudden Infant Death Syndrome. Alterations in nicotinic acetylcholine receptor signaling (nAChRs) after DNE lead to changes in excitatory neurotransmission in neural networks that control breathing, including a heightened excitatory response to AMPA microinjection into the hypoglossal motor nucleus. Here, we report on experiments designed to probe possible postsynaptic and presynaptic mechanisms that may underlie this plasticity. Pregnant dams were exposed to nicotine or saline via an osmotic mini-pump implanted on the 5th day of gestation. We used whole-cell patch clamp electrophysiology to record from hypoglossal motoneurons (XIIMNs) in thick medullary slices from neonatal rat pups (N= 26 control and 24 DNE cells). To enable the translation of our findings to breathing-related consequences of DNE, we only studied XIIMNs that were receiving rhythmic excitatory drive from the respiratory central pattern generator. Tetrodotoxin was used to isolate XIIMNs from presynaptic input, and their postsynaptic responses to bath application of L-glutamic acid (glutamate) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were studied under voltage clamp. DNE had no influence on inward current magnitude evoked by either glutamate or AMPA. However, in cells from DNE animals, bath application of AMPA was associated with a right shift in the amplitude distribution (P = 0.0004), but no change in the inter-event interval distribution of miniature excitatory postsynaptic currents (mEPSCs). DNE had no influence on mEPSC amplitude or frequency evoked by glutamate application, or under (unstimulated) baseline conditions. Thus, in the presence of AMPA, DNE is associated with a small but significant increase in quantal size, but no change in the probability of glutamate release.

Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons

“…Much work on the neuropathology of SIDS has focused on the role of brainstem serotonin signaling (Haynes et al, ; Kinney, Richerson, Dymecki, Darnall, & Nattie, ), and the link to chemosensation (Buchanan, Smith, MacAskill, & Richerson, ; Ray et al, ), the hypoxic response of the respiratory network (J. M. Ramirez, Folkow, & Blix, ; S. Ramirez et al, ; Tryba, Pena, & Ramirez, ), and arousal (Buchanan & Richerson, ; Iwasaki et al, ; Mateika, Komnenov, Pop, & Kuhn, ). Yet many aspects of cardiorespiratory control also depend on cholinergic mechanisms, and are altered by nicotine exposure (Cerpa et al, ; Shao & Feldman, ; Vivekanandarajah, Waters, & Machaalani, ), including the respiratory chemosensory response (Coddou, Bravo, & Eugenin, ; Eugenin et al, ), and multiple aspects of upper airway control (Cholanian, Powell, Levine, & Fregosi, ; Cholanian, Wealing, Levine, & Fregosi, ; Powell, Levine, Frazier, & Fregosi, ; Wollman, Levine, & Fregosi, ). Chat‐Vglut2 tdT expression identifies two known groups of cholinergic/glutamatergic neurons in the medulla, located in IRt and RVLM.…”

Interaction of Valproic Acid vs. Neurotransmitters and the Relationship to Nicotine by the Quantum Method

“…[12,14] This alkaloid modifies the concentration of some neurotransmitters (NT) and their particular function. [15][16] NIC consumption develops tolerance and withdrawal symptoms. [17][18] The release of several NT mediated the action of the alkaloid: acetylcholine, beta endorphin, dopamine, norepinephrine, and serotonin (5-HT).…”