Understanding Neural Connections
In graduate school you initially test out different labs by doing short-term research projects with different professors. While I tested subjects as varied as evolution and biochemistry, I still found myself drawn to neuroscience. I joined the laboratory of Kang Shen in order to study how neurons set-up connections to each other and other tissues. These connections are called synapses, and they are what allows the brain to transmit signals so that you can understand the sentences you just read.
From Scientific American and adapted from the Worm Atlas. C. elegans is a 1 mm long nematode worm. It is the only organism where the connections of all the neurons to each other has been mapped out. The connectome, or map of connections, was made possible by the fact that C.elegans has only 302 neurons. The combination of the relative simplicity of the worm and the highly detailed understanding of its development make it an amazing tool to study how neurons are able to form specific connections that are pictured in this image.
The formation and maintenance of the proper number of synapses is crucial to proper signaling in the brain. In many systems, synapse number is dynamic. An excess of connections is formed early in development and then the number decreases as neuronal activity strengthens the connections that are needed. Improper regulation of synapse number is associated with some forms of mental retardation and a reduced number of synapses is a strong correlate of cognitive impairment in Alzheimer’s Disease.
Schematic of the neuron (DA9) that I studied. DA9 forms connections on to muscle, as represented by the red puncta.
In order to study how a neuron maintains a certain number of synapses I use a nematode worm called C.elegans. C. elegans means “elegant incandescent rod” in latin, and the more time I spend with them, the more elegant they seem. They are small. At only 1 mm long, their adult form is barely visible to the naked eye. Yet, they are one of the best understood organisms in the history of science. Each worm has only 959 cells, and the history of each cell is nearly identical from worm to worm. This allowed researchers to create a map of the cells in the worm and a lineage tracing the history each of the 959 cells. In total, there are 302 neurons, and each one has a name. This incredible detail allows us to understand subtle changes in the history of the neurons.
Comparison of a normal, or wild-type, DA9 neuron to a mutant DA9 neuron. The mutant, mtm-6, causes the neuron form fewer connections on to muscle. The bracket shows the length of the mutant synapse region, which is shorter than the wild-type. The asterisk marks the cell body of the neuron.
The neuron I studied is in the tail and forms a series of connections on to muscle. Madina Tugizova, an undergraduate in the lab working with Kerri Spilker, found that loss of a gene called mtm-6 caused fewer synapses. I’ve worked to understand how the loss of this genes caused the reduction in synapse number.
Additionally, as I studied the pattern of connections in the neuron, I noticed that there was a shift in where the synapses were forming. Further research demonstrated that this shift is linked to a secreted signal that the lab previously studied. Based on prior research we knew the signal is secreted from the tissue around the neuron. Our data that suggested that mtm-6 regulates the secretion of the signal from surrounding tissue, but regulated the number of connections from the neuron itself.