The head-fixed behaving rat—Procedures and pitfalls

Abstract

This paper describes experimental techniques with head-fixed, operantly conditioned rodents that allow the control of stimulus presentation and tracking of motor output at hitherto unprecedented levels of spatio-temporal precision. Experimental procedures for the surgery and behavioral training are presented. We place particular emphasis on potential pitfalls using these procedures in order to assist investigators who intend to engage in this type of experiment. We argue that head-fixed rodent models, by allowing the combination of methodologies from molecular manipulations, intracellular electrophysiology, and imaging to behavioral measurements, will be instrumental in combining insights into the functional neuronal organization at different levels of observation. Provided viable behavioral methods are implemented, model systems based on rodents will be complementary to current primate models—the latter providing highest comparability with the human brain, while the former offer hugely advanced methodologies on the lower levels of organization, for example, genetic alterations, intracellular electrophysiology, and imaging.

Choice ball: a response interface for two-choice psychometric discrimination in head-fixed mice

“…Our device has several advantages over previously used methods. By divorcing the animal's method of acquiring reward (licking) from its method of choice response (paw motion), our paradigm does not require conditioning the animal to suppress anticipatory licking (Andermann et al 2010;Schwarz et al 2010) and leaves lick rate available as an additional behavioral metric. By providing high-resolution trackball movement data, our device opens an additional facet of the animal's choice response to analysis that is lost in experiments with a binary readout, the ability to detect and study changes of mind.…”

“…Likewise, epochs of relative disengagement in Go/No-Go tasks are difficult to differentiate from a preference for No-Go responses. For these reasons, the process of making an active choice response on each trial makes behavior in 2AFC tasks considerably easier to interpret (Schwarz et al 2010). Moreover, the symmetrical reward contingencies of 2AFC tasks enable reaction time measurements that are not confounded by choice-specific motivational factors typical in Go/No-Go task designs (Zariwala et al 2006).…”

“…Studies conducted in awake head-fixed mice that require a behavioral choice readout have previously been limited to Go/No-Go behavioral responses (Andermann et al 2010;Histed et al 2012;Komiyama et al 2010;Mehta et al 2007) or virtual navigation (Harvey et al 2009). Although considerable progress has been made using these classes of behavior in the rodent, epochs of disengagement and impulsivity in Go/No-Go tasks complicate the interpretation behavioral choices (Schwarz et al 2010;Stüttgen et al 2006;Stüttgen and Schwarz 2008).…”

Flat-floored Air-lifted Platform: A New Method for Combining Behavior with Microscopy or Electrophysiology on Awake Freely Moving Rodents

“…Indeed, even though in the studies where head fixation was done under anesthesia and the actual experiments were started after a brief waiting period 13 , one cannot exclude possible long-lasting effects of the brief anesthesia episode on the experimental data. Other studies have relied on water deprivation for systematic habituation of the animals to head fixation and used water reward as the means of motivating the animal to remain immobile 36 . However, the reward-based head fixation method limits the choice of applicable behavioral tests and, importantly, occupies one of the wellestablished stimulus-reward associations.…”

Design and performance of an ultra-flexible two-photon microscope for in vivo research

“…The head fixed preparation, known for its wellcontrolled psychophysical conditions (stimulus delivery and response monitoring) in nonhuman primate studies, has been adapted to rodents by numerous groups [14][15][16][17][18][19]. Twophoton imaging of lateral cortical regions in awake, head-fixed animals poses a problem, since tilting the animal to adjust the imaging plane to be tangential to the cortical surface should be avoided.…”