Playing Quake with a Real Mouse

Most people play Quake with a computer mouse, but researchers in David Tank’s lab at Princeton have done it with a living mouse, AND they are recording the intracellular activity of individual neurons of the mouse during the gaming session. As reported in Intracellular dynamics of hippocampal place cells during virtual navigation, the virtual reality environment of the video game was sufficiently realistic to generate place cell activity in the mouse’s hippocampus. 

Now where did I see that cheese power-up?

Place cells modulate their activity dependent on the location the mouse is at. They have mostly been identified with extracellular recordings in freely moving mice. Extracellular recording only permits the detection of the rates of action potential firing, rather then the subtle intracellular voltage changes that could help explain the mechanism of place cell activity generation.  A few pioneers, such as Albert “my greatest strength is a tremendous capacity for boredom” Lee, have recorded intracellularly in freely moving animals, but these experiments are fiendishly difficult, as the motion of the animal’s head tends to break the seal on the recorded neuron.  Only a few cells have been recorded in that manner for more than a few minutes, though the success rate has been improving recently.  

Experimental setup

In Chris Harvey’s technique, they fix the head of the mouse to a bar and let the mouse walk on a floating ball, while a virtual reality screen is projected in the mouse’s field of view.  The motion of the ball controls the motion on the screen.  The head never moves, so intracellular recordings can be made relatively easily and held for long periods of time.

The authors find three characteristics of place cell activity that could explain their generation and function.

“An asymmetric ramp-like depolarization of the baseline membrane potential, an increase in the amplitude of intracellular theta oscillations, and a phase precession of the intracellular theta oscillation relative to the extracellularly recorded theta rhythm.” 

Intracellular voltage dynamics in place cells

These could be used to explain how place cells remap their selectivity when a mouse (or a human) moves into a new environment.  This also could be used to do more in depth studies of the mental replay of place locations that has been previously recorded in the activity patterns of the hippocampus.  The technique itself is about as sexy as neuroscience gets.  Unfortunately, this paper also provides an additional piece of evidence for Karel to use in motivating lab post-docs, “Look at Chris, he left the lab after you got here and already has a Nature article…”‘