Cell's Tiny Power Source Critical For Synapse Function

Each living cell is a miniature breathing, eating, waste-expelling organism. Hundreds or thousands of little footprint-shaped mitochondria generate energy for cell functions from sugar and oxygen. They are particularly important in brain cells, where they perform additional jobs related to signaling and programmed cell death, but little is known about how their distribution and movement relates to the synaptic activity crucial for learning and memory, said Morgan Sheng, the Menicon Professor of Neuroscience at MIT and an investigator with the Howard Hughes Medical Institute.

Compared with most cells, neurons are more elongated and complex. Neurons are divided into different sections: the long, thin axon and the branching, tree-like dendrites that receive signals from other neurons via the suction cup-shaped synapses. Synapses, tiny gaps separating neurons, consist of a presynaptic ending at the very tip of an axon that contains neurotransmitters, a postsynaptic ending that contains neurotransmitter receptor sites, and the space between the two endings. Both presynaptic and postsynaptic endings require the energy generated by mitochondria.

Critical functions, such as synapses' transmission of information and ability to change rapidly in response to stimuli, are managed by distant cellular compartments that can become isolated from their nearest mitochondria. Sheng and postdoctoral fellow Zheng Li explored whether having the power source far away, like a too-distant room heater, would affect synaptic function.

The researchers looked at mitochrondria in living hippocampal neurons. The hippocampus, a seahorse-shaped brain region in the temporal lobe, is known to play a critical role in memory.

When synapses were stimulated, the researchers found, mitochrondria in the dendrites changed from being long and thin to more aggregated, collecting in globules near the enlarged dendritic spines, as if the mitochondria were reporting for duty at the active part of the neuron.

"Our studies reveal that mitochrondria dynamically redistribute into dendritic protrusions in response to synaptic excitation … The dendritic distribution of mitochondria appears to be an essential and limiting factor for synaptic density and plasticity," the authors wrote. If mitochondria don't migrate into the distant reaches of the dendrites--where most synapses are present--the synapses become less numerous and lose some of their ability to respond to external input. Enhancing mitochondria with the nutrient creatine also promoted synaptic density, the study showed.

These findings on mitochondrial function correlate with the fact that neurodegenerative diseases such as Alzheimer's and Parkinson's are associated with abnormal mitochondria. The synapse loss characteristic of these diseases may stem in part from mitochondrial dysfunction, the authors write.

In addition to Li and Sheng, authors include Picower Center researchers Yasunori Hayashi, assistant professor of brain and cognitive sciences, and postdoctoral associate Ken-Ichi Okamoto.

This work is funded by the Howard Hughes Medical Institute.