Researchers at the Allen Institute have uncovered subtle but intriguing differences between a mouse and human neuron of the same kind. The differences they found could have implications for studying human brain disorders or brain therapies in laboratory mice.
Looking at living neurons from one region of the cortex, the outermost part of the mammalian brain that is responsible for our higher cognitive functions, the research team found that one kind of human neuron sends and receives electrical signals in a different way than does the mouse version of the same cell. The researchers published a study in print today in the journal Neuron describing their comparison.
The researchers found that the human neurons are studded with groups of proteins known as h-channels, while the mouse cells of this class are largely devoid of h-channels.
That finding could have implications for mouse models of human brain disorders and for drug development studies, the researchers said. If drugs are developed that act on h-channels, they’d likely have different effects in humans than they would in mouse studies, which are often a necessary precursor to clinical trials.
“If human neurons have different electrical properties than rodent neurons of the same type, it has implications for how you identify dysfunctions relevant to a brain disorder, or even how you’d test a new therapeutic and how it works,” said Jonathan Ting, Ph.D., a neuroscientist at the Allen Institute for Brain Science, a division of the Allen Institute, and senior author on the study.
That’s not just a hypothetical concern. An existing epilepsy drug, lamotrigine, acts in part by changing h-channel activity. The research team hasn’t yet shown that the human and mouse neurons respond differently to different drugs — that’s on their future to-do list. But because h-channels act as a gatekeeper between the neuron and its environment, letting in or out certain atoms during brain signaling in response to changes in voltage across the cell surface, it’s reasonable to assume these channels could affect how the brain responds to some drugs which would also act from the outside of the cell.
