Slow angled-descent forepaw grasping (SLAG): an innate behavioral task for identification of individual experimental mice possessing functional vision

Behavioral and Brain Functions Gil-Pags et al. 0 Initiative to Maximize Student Diversity (IMSD), Mayo Clinic , Rochester, MN , USA 1 Undergraduate Research Employment Program (UREP), Mayo Clinic , Rochester, MN , USA 2 Departamento de Psicologia Biologica y de Salud, Programa de Licenciatura de Psicologia, Universidad Autonoma de Madrid , Madrid , Spain 3 College of Medicine, Mayo Clinic , Rochester, MN , USA 4 MD/PhD program, Mayo Medical School (MMS), Mayo Clinic , Rochester, MN , USA 5 PhD program, Mayo Graduate School (MGS), Mayo Clinic , Rochester, MN , USA 6 Summer Undergraduate Research Fellowship (SURF) program, Mayo Clinic , Rochester, MN , USA - Slow angled-descent forepaw grasping (SLAG): an innate behavioral task for identification of individual experimental mice possessing functional vision Gil-Pags et al. Behavioral and Brain Functions 2013, 9:35 http://www.behavioralandbrainfunctions.com/content/9/1/35 Open Access Slow angled-descent forepaw grasping (SLAG): an innate behavioral task for identification of individual experimental mice possessing functional vision Background: There is significant interest in the generation of improved assays to clearly identify experimental mice possessing functional vision, a property that could qualify mice for inclusion in behavioral and neuroscience studies. Widely employed current methods rely on mouse responses to visual cues in assays of reflexes, depth perception, or cognitive memory. However, commonly assessed mouse reflexes can sometimes be ambiguous in their expression, while depth perception assays are sometimes confounded by variation in anxiety responses and exploratory conduct. Furthermore, in situations where experimental groups vary in their cognitive memory capacity, memory assays may not be ideal for assessing differences in vision. Results: We have optimized a non-invasive behavioral assay that relies on an untrained, innate response to identify individual experimental mice possessing functional vision: slow angled-descent forepaw grasping (SLAG). First, we verified that SLAG performance depends on vision and not olfaction. Next, all members of an age-ranged cohort of 158 C57BL/6 mice (57 wild-type, 101 knockout, age range 44241 days) were assessed for functional vision using the SLAG test without training or conditioning. Subjecting the population to a second innate behavioral test, Dark Chamber preference, corroborated that the functional vision assessment of SLAG was valid. Conclusions: We propose that the SLAG assay is immediately useful to quickly and clearly identify experimental mice possessing functional vision. SLAG is based on a behavioral readout with a significant innate component with no requirement for training. This will facilitate the selection of mice of known sighted status in vision-dependent experiments that focus on other types of behavior, neuroscience, and/or cognitive memory. Background The visual system is of outstanding interest in behavioral and neural sciences. Historically, the anatomy of the eye and its neuronal associations made the system accessible to mapping the pathways that encode sensation and perception of an external stimulus in the brain [1-3]. Modern experimentation in behavioral neuroscience often relies on test subjects visual capacity to accomplish requisite tasks. In mice, as nocturnal rodents, olfaction and hearing are * Correspondence: 7College of Medicine, Mayo Clinic, Rochester, MN, USA Full list of author information is available at the end of the article considered the more dominant senses for perception of objects at a distance; however, mouse vision is appreciated as an important contributing sense despite an estimated 20/2000 acuity [4,5]. Cognitive memory experiments in mice often require the measurement of responses to visual cues. Because of this, such memory assays themselves can sometimes be used to detect differences in mouse visual acuity [6-8]. This requires the assumption or demonstration that the mice involved possess equivalent memory capacity, allowing differences in performance to be attributed to differences in vision. Common memory assays that have been applied in this way include some that are maze-based, or involve Pavlovian cue/context fear conditioning, or conditioned suppression of specific behaviors [9]. However, quite often the converse experiment is desirable, such that cognitive memory capacity can be treated as the variable, when baseline visual performance can be considered equivalent between responding mice. There is a recognized need in the field for assays that would improve identification of individual mice possessing functional vision that are to be used in subsequent behavioral/memory experiments [9]. Ideally, such assays should be robust, reproducible, simple, and economical, require no mouse behavioral training or conditioning, and require no behavior-altering procedures such as whisker (vibrissae) trimming or tail amputation. Two common procedures examine vision-based behavioral reflexes in the mouse: eye-blink and visual placing (forepawreaching) tests [10]. Both invoke a response to an object approaching the eye: in the eye-blink test, a cotton swab approaching the eye induces the mouse to wince or blink, while in the visual placing test, descent of a suspended mouse toward an incoming flat surface induces a forward stretching motion of the forepaws. However, vision is not the only sense that can induce these responses, which can also occur if the whiskers or nose are touched during either procedure. Furthermore, expression of these reflexes in sighted mice can sometimes appear ambiguous. A third reflex-based functional vision assessment tool has not yet been adopted for general use as a pre-test in cognitive behavioral studies, but holds outstanding promise for potential general application in this field: Optokinetic tracking involves assessment of the optokinetic reflex with an optokinetic drum [11-15]. Conceivably, the instrumentation and procedures involved could be optimized and/or validated in a minimally invasive, behavior non-modifying format to identify individual sighted mice for subsequent behavioral experimentation. Beyond reflexes, two common tests rely on untrained behavioral responses to visual depth perception: visual cliff [16] and elevated-plus maze [17] tests. However, since up to 10% of mice from the best performing strains can fail, these tests may be most suitable for general strain characterization, while they somewhat more cautiously supply the sighted vs. blind status for each individual mouse [9]. Vision scoring errors on these tests may occur due to the use of other senses to perceive and judge distances, or variation in innate fear vs. exploratory impulses during task performance [18]. We have prepared a simple, economical, behavioral assay that uses an untrained, innate behavioral response to identify individual experimental mice that possess functional vision: slow ang (...truncated)