I can just hear Sarah Palin now: “And sometimes taxpayer money goes to projects . . . where scientists get paid to tickle mouse whiskers. I kid you not!”
As funny as it sounds, a group of scientists out of Johns Hopkins University did precisely that. They stimulated single whiskers on mice while using two-photon microscopy on mouse sensory cortex to study just how stimulation changed glutamate receptor availability. (Glutamate is the primary excitatory neurotransmitter in the brain.) They found that following stimulation, the number of surface AMPA receptors (AMPAR) dramatically increased in pre-existing spines by about 30%. Interestingly, this increase occurred within 1 hour of the start of stimulation and persisted for at least 3 hours following its cessation.
Spines in whisker-stimulated and control animals. The arrows in the control denote the consistency in AMPAR levels, while below they indicate increased AMPAR subunit A1 expression. The AMPAR subunit A2 is marked in violet, while the A1 subunit is green. Overlap is shown as white, indicating that the AMPAR Glu A1 subunit dramatically increases.
Not all dendrites showed such increases in AMPAR availability. For instance, Zhang et al. (2015) report that only 11 out of 52 dendrites studied showed increased Glu A1 intensity, but within those 11, intensity was increased by an average of 202%. This suggests that neurons in layers II/III can show high stimulus selectivity, even within the same neuron.
The team also found smaller spines were much more likely to increase in size and AMPAR content than larger spines following whisker stimulation, indicating that pre-existing spinal properties strongly influence their propensities for change.
Long-term potentiation (LTP) is a strengthening of synapses based on previous activity, which is usually NMDA receptor-dependent, and it is roughly equated with the molecular process of “learning”. NMDA receptors (NMDAR) bind the excitatory neurotransmitter, glutamate, opening ion channels that allow sodium and calcium into the cell. Calcium in particular is important for controlling LTP given that the ion sits upstream of many cellular functions.
Zhang et al. found that when they applied an NMDAR antagonist to mouse cortex during whisker stimulation, AMPAR increase was completely blocked, indicating that the previous increase was completely NMDAR-dependent. Another characteristic of LTP is its propensity to be long-lasting. The researchers found that an increase in Glu A1 intensity in dendritic spines, though it decreased somewhat by 6 hours after stimulation, was still moderately present up to 48 hours post-stimulation. Thus, whisker stimulation, through an NMDAR-dependent process, leads to LTP and “learning”.
So, yes, some scientists get paid to tickle mouse whiskers for a living. And from it, we discover more about the basis of how we learn.