Researchers at Seattle Children’s Research Institute have discovered that populations of neurons in the brain stem have a previously unrecognized susceptibility to disruption by nicotine during early brain development.
Published in the Journal of Comparative Neurology, their findings offer a clue to how nicotine exposure in utero could have a lasting effect on the brain’s wiring and give rise to negative outcomes like sudden infant death syndrome (SIDS).
Researchers zero in on morphing neurons affected by nicotine
In the paper, authors Drs. Nino Ramirez and Eric Turner in the research institute’s Center for Integrative Brain Research combined their experience looking at unusual neurons found deep in the brain that co-express glutamate, the major excitatory neurotransmitter used in the brain, and acetylcholine, a more specialized neurotransmitter.
Ramirez previously found neurons with these characteristics in a circuit just above the spinal cord that regulates breathing. Turner described their presence in the habenula, which is implicated in the regulation of mood and nicotine addiction. Together, they wanted to learn what other neurons in the brain shared the property of expressing both neurotransmitters together.
Using a genetic trick in mice, they mapped all the neurons in the brain that express acetylcholine and glutamate. As expected, this system marked the neurons previously reported. Surprisingly, it also marked new populations of neurons in several other areas of the brain relevant to cognition, motor control, arousal in response to distress and respiration. A closer look revealed they appeared to be glutamatergic, excitatory neurons that unexpectedly express acetylcholine early in brain development and then turn it off as the brain matures.
Findings point to new areas of the brain where nicotine could disrupt development
Nicotine, which acts by binding to acetylcholine receptors, can disrupt any brain circuit that uses acetylcholine as a signal. Because this research strongly suggests acetylcholine is needed to establish pathways in the developing brain, the authors hypothesize nicotine exposure in utero could potentially cause abnormalities in these circuits.
“Our findings point to new areas in the brain where nicotine could act a developmental disruptor and could be important to understanding sudden infant death syndrome,” Turner said, noting that while maternal smoking has long been associated with bad outcomes for babies, including SIDS, a mechanism for the direct and lasting effect of nicotine on brain development has been poorly understood.
Ramirez added, “A major contributor to SIDS is the failure to arouse from respiratory distress. You can begin to imagine if the brain circuit that is responsible for arousal from suffocation doesn’t develop properly, how that could lead to this devastating cause of death in infants less than a year old.”
As a next step, the researchers plan to perform further studies to define the roles and functions of the newly discovered neurotransmitter properties of these neurons.
- Link to the full paper, “Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons”
- Researchers discover area of the brain that controls breathing