Chronic, episodic nicotine exposure alters GABAergic synaptic transmission to hypoglossal motor neurons and genioglossus muscle function at a critical developmental age.

Regulation of GABAergic signaling through nicotinic acetylcholine receptor (nAChR) activation is critical for neuronal development. Here, we test the hypothesis that chronic episodic developmental nicotine exposure (eDNE) disrupts GABAergic signaling, leading to dysfunction of hypoglossal motor neurons (XIIMNs), which innervate the tongue muscles. We studied control and eDNE pups at two developmentally vulnerable age ranges: postnatal days (P)1-5 and P10-12. The amplitude and frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs, mIPSCs) at baseline were not altered by eDNE at either age. In contrast, eDNE increased GABAAR-α1 receptor expression on XIIMNs and, in the older group, the postsynaptic response to muscimol (GABAA receptor agonist). Activation of nAChRs with exogenous nicotine increased the frequency of GABAergic sIPSCs in control and eDNE neurons at P1-5. By P10-12, acute nicotine increased sIPSC frequency in eDNE but not control neurons. In vivo experiments showed that the breathing-related activation of tongue muscles, which are innervated by XIIMNs, is reduced at P10-12. This effect was partially mitigated by subcutaneous muscimol, but only in the eDNE pups. Taken together, these data indicate that eDNE alters GABAergic transmission to XIIMNs at a critical developmental age, and this is expressed as reduced breathing-related drive to XIIMNs in vivo.NEW & NOTEWORTHY Here, we provide a thorough assessment of the effects of nicotine exposure on GABAergic synaptic transmission, from the cellular to the systems level. This work makes significant advances in our understanding of the impact of nicotine exposure during development on GABAergic neurotransmission within the respiratory network and the potential role this plays in the excitatory/inhibitory imbalance that is thought to be an important mechanism underlying neonatal breathing disorders, including sudden infant death syndrome.

Translating evidence-based parenting programs for primary care: Stakeholder recommendations for sustainable implementation.

AIMS: To translate evidence-based programs (EBP) for a new setting, attention must be given to the characteristics of the intervention and the local setting, as well as evidence that is compelling to decision-makers. This paper describes the history of a partnership and stakeholder recommendations to inform the adaptation of an EBP for primary care. METHODS: We established a community advisory board (CAB) consisting of stakeholders with expertize in primary care delivery. A thematic analysis was conducted with fieldnotes and transcriptions from CAB meetings and regular meetings with participating clinics. RESULTS: We found that (a) parenting programs with a focus on behavioral and physical health are appropriate for this setting, (b) variability in the structure of primary care means implementation must be tailorable, and (c) financial and organizational outcomes are compelling for decision-makers. CONCLUSION: Factors related to the content and structure of evidence-based programs are uniquely related to distinct implementation outcomes of interest to key stakeholders.