Cellular bursts of energy may play a larger role in healthy development than researchers ever imagined. Scientists at Emory University School of Medicine have discovered that when circuits within the spinal cords of embryos create short bursts of energy, called spontaneous network activity (SNA), it also aids the normal development of synaptic connections. Synapses, highly focused links between cells, create neural circuits that enable coordination within the nervous system and support physical movement and the effective maturation of organs, senses and muscles.
The discovery is reported in the February 16 issue of the journal "Neuron." Peter Wenner, PhD, assistant professor in Emory's Department of Physiology, is lead investigator of the study. Carlos Gonzales-Islas, PhD, postdoctoral fellow in physiology, is first author of the paper.
Keeping an even level of spontaneous network activity allows synapses to mature and perform normally, and the presence of too much or too little SNA could alter synaptic strength with negative developmental consequences.
Scientists had previously shown that SNA is generated by both excitatory and inhibitory neurotransmitters, which serve to transmit messages between cells and neurons. Excitatory neurotransmitters signal for an increase of activity, and inhibitory neurotransmitters signal for a decrease in activity. However, the neurotransmitters that will become inhibitory in adulthood can inspire network activity in early development.
"Those same neurotransmitters that produce inhibition in adults actually produce excitation in the embryo," Dr. Wenner explains. "As excitatory synapses and the synapses that will become inhibitory in adulthood grow in strength, they also appear to act to maintain an appropriate level of SNA."
SNA causes fetal kicking, which itself induces healthy development of muscles, joints and bones. However, though fetal kicking is indisputably important, the large amount of energy needed to make this network activity and subsequent movement possible seemed inordinate, leading Dr. Wenner to wonder if perhaps the SNA served another purpose. In addition, the presence of SNA in other areas of the body -- including the brain and eyes -- clearly had no connection to fetal kicking.
The study built on an earlier finding that showed if drugs preventing activity were introduced, the network would compensate by strengthening the connection -- or level of excitability -- of the neurotransmitters. In effect, decreasing network activity stimulated increased power of synapses, at least in tissue cultures. As Dr. Wenner says, "It is a compensatory synaptic response. Our idea was that maybe activity in the spinal cord could maintain itself in the same way that these tissue cultures do. If the activity were reduced, the system would act to increase the connection strength of the excitatory synapses and make the spinal cord more excitable."
Dr. Wenner and Dr. Gonzalez-Islas began by inserting a drug into chick embryos to stop virtually all spontaneous network activity. After two days of dramatically reducing the activity, the scientists examined the strength of the synaptic connections of individual cells within the spinal cord. As projected, they found that the amplitude, or strength, of the connections, had increased by 50 percent.
In addition, the researchers observed that the early excitatory synapses that will later become inhibitory also had strengthened synaptic connections, playing their own part in compensating for the activity-reducing drugs. The similar reactions indicate that both types of synapses can be affected by the same variables, and subsequently act the same way to achieve a balanced development of excitatory and inhibitory synapses.
The study was funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke.