Novel MultiMAP Technique Measures Neural Mechanisms Underlying Alertness
Excessive alertness has been linked to several mental disorders including PTSD, depression, anxiety, and mania. Scientists at Stanford University recently developed a new technique for visualizing neuronal activity to examine the origins of “alertness” in the brain.
The technique, termed multiplexed-alignment of molecular and activity phenotypes or MultiMAP, exhibits excellent spatial and temporal resolution. It circumvents the need for transgenic techniques by allowing real-time recording of neural activity and, subsequently, identification of active neurons.
In the Stanford study, researchers used MultiMAP to record brain activity in zebrafish as they were exposed to aversive stimuli. This caused them to become “alert” and move their tails which then triggered the influx of signaling molecules in neurons. The activated brain regions were bioengineered to display a fluorescent signal.
The fluorescent signal was measured as fish responded to stimuli, and brain imaging provided accurate visualizations of which neurons were activating. The brains were then labeled with fluorophore-linked antibodies specific to proteins expressed in different types of cells modulating neuronal activity.
The brains were imaged once more to map the specific neurons involved in alertness. Scientists discovered several circuits containing cholinergic, serotonergic, dopaminergic and CART neurons, which are believed to be involved in different aspects of alertness. The findings also reaffirmed the role of norepinephrine-secreting neurons projecting from the brainstem.
The team repeated the experiment on mice, slightly altering the procedure by optogenetically stimulating the mice’s brainstems. Their results aligned with the zebrafish data indicating that alertness circuits are highly conserved across species.
Karl Deisseroth, one of the scientists, states that “this tight conservation of alertness-promoting circuits over such long epochs of evolutionary time… strongly implies relevance to humans as well.”
These findings not only bring us one step closer to developing future treatments for alertness-linked disorders but also establish MultiMAP as a useful mapping tool in many subfields of neuroscience.