Fitting behavior inside a 40x40x40 cm box

The central question in neuroscience is to understand the physical basis of behavior. But what kinds of behavior can be studied in a lab? Mice and rats can be placed in chambers and mazes to perform tasks. One can then study the effects of lesions on behavior. But if cell recordings are performed the constraints are much more severe. Until just a few years ago, this required a fair amount of cabling to link the brain to signal amplifiers and other electronics. Experiments in primates are performed in a “monkey chair” that keeps the animal’s body and head in place. Humans, of course, are studied inside MRI tubes that are anything but organic. With the technology available, getting closer to natural behaviors has simply not been possible.

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A type of behavior that fits inside a 40x40x40 cm box is classical conditioning.  Indeed, it has been extensively studied by psychologists since the early twentieth century, and for those interested in studying the biological mechanisms of fear, the paradigm has been a godsend. It has offered a window into this process, while allowing careful control over experimental variables, a fundamental consideration in experimental science. With the paradigm, the neuroscience of fear has been one of the most active areas of inquiry.

The fixation with this paradigm has also incurred nontrivial costs, leading to led to a type of tunnel vision[1]. As Dennis Pare and Gregory Quirk, very prominent “fear” researchers themselves, state:

When a rat is presented with only one threatening stimulus in a testing box that allows for a single reflexive behavioral response, one is bound to find exactly what the experimental situation allows: neuronal responses that appear tightly linked to the CS and seem to obligatorily elicit the conditioned behavior. Paré, D., & Quirk, G. J. (2017, p. 6)

The very success of the approach has led to shortsightedness.

Placed inside a small, enclosed chamber the animal is limited to a sole response: upon detecting the CS, it ceases all overt behavior and freezes in place. It can’t consider other options, such as dashing to a corner to escape; it cannot try to attack the source of threat either, as there isn’t another animal around – the shock comes out of nowhere! Now, when researchers study the rat’s brain under such conditions, a close relationship between brain and behavior is established. But as Pare and Quirk warn, the tight link might be apparent insofar as it would not hold under more general conditions. Neuroscience is experiencing a methodological renaissance. Advances in chemistry and genetics allow precision in targeting regions and circuits in a way that would have sounded like science fiction a decade ago. But if we continue using the paradigms that have been the mainstay of field, we will be cornering ourselves into a scientific cul-de-sac[2]. It’s time to think outside the box.

[1] Text here builds directly from Paré, D., & Quirk, G. J. (2017). When scientific paradigms lead to tunnel vision: lessons from the study of fear. npj Science of Learning, 2(1), 6.

[2] “Cul-de-sac” expression inspired by Kim and Jung (2018).