Narcolepsy, a brain disorder that affects a patient's sleep-wake
cycle, is caused by the loss of a peptide - a short chain of amino
acids - called orexin/hypocretin in the brain.
Now, research has shown that natural release of
orexin/hypocretin generates a unique signature of brain
activity.
The work was led by Dr Denis Burdakov at the Medical Research
Council's National Institute for Medical Research (NIMR; now part
of the Francis Crick Institute). He explained: "Like a swan
smoothly gliding on water with frantic paddling underneath, the
orexin system is thought to make numerous computations and
corrections to make consciousness flow smoothly from one state to
the next.
"However, beyond this normally smooth surface, control signals
generated by orexin remain hidden from sight, and so it is not
clear why loss of orexin produces unstable consciousness."
Dr Burdakov's team stimulated the orexin circuit and measured
outputs of brain histamine cells (which stimulate wakefulness,
explaining drowsiness caused by anithistamine drugs) . This enabled
them to obtain experimental estimates of the input-output
computations performed by orexin in the brain.
The results suggest that orexin is required for generating a
unique kind of brain activity - sustained and integrative impulses
in brain cells that promote wakefulness. These kinds of signals
could not be generated by glutamate, one of the most common
signalling molecules (neurotransmitters) in the brain. The findings
help to explain why the brain uses energy making peptide
neurotransmitters such as orexin/hypocretin in addition to
glutamate.
Dr Burdakov said: "The results are interesting because they
suggest a specific task for which orexins are required in brain
circuits.
"Our study offers new insights into the brain signals that are
lacking in people with narcolepsy and point to processes that need
to be mimicked by treatments for the condition."
The paper, Coreleased orexin and glutamate evoke nonredundant spike outputs
and computations in histamine neurons, is published in Cell
Reports.