Chronic, episodic developmental nicotine exposure alters GABAergic synaptic transmission to hypoglossal motor neurons at a critical developmental age in rats

Abstract

The adverse effects of nicotine exposure on brain structural and functional development is attributed to its action on the nicotinic acetylcholine receptors (nAChRs). nAChRs are expressed post‐synaptically on hypoglossal motor neurons (XIIMNs), the neurons that innervate the tongue. We recently showed that chronic, episodic developmental nicotine exposure alters the intrinsic properties of these neurons, which may be one mechanism to explain impaired tongue muscle function that is commonly observed in nicotine‐ exposed human and animal neonates. Importantly, along with the intrinsic properties of XIIMNs, the balance of excitatory and inhibitory fast‐synaptic inputs to these neurons is important in dictating the strength of motor output to the tongue. nAChRs are also located on the soma, dendrites, and axon end terminals of excitatory and inhibitory interneurons that synapse onto XIIMNs, activation of which increases action potential firing and neurotransmitter release. Here, we tested the hypothesis that chronic, episodic developmental nicotine exposure alters GABAergic transmission, a major source of fast‐synaptic inhibition, to XIIMNs. XIIMNs were recorded in brainstem slices from control and nicotine‐ exposed rats in two age groups: postnatal days (P)1‐5 and P10‐12, which is considered a critical period of brain development. In voltage‐ clamp mode, the frequency of GABAergic spontaneous inhibitory post‐synaptic currents (sIPSCs) was recorded at baseline and in response to activation of nAChRs with acute, bath‐applied nicotine. The baseline frequency of GABAergic sIPSCs was not different between control and nicotine‐exposed neurons at either age. In the P1‐5 age group, acute nicotine increased the frequency of GABAergic sIPSCs in both control and nicotine‐exposed neurons. However, at ages P10‐12, acute nicotine increased the frequency of GABAergic sIPSCs in nicotine‐exposed neurons, but had no effect in control neurons. These findings indicate that chronic, episodic nicotine exposure alters GABAergic synaptic transmission to XIIMNs at a critical developmental age, and may contribute to excitatory/inhibitory imbalance that underlies impaired control of the muscles of the tongue.