Procedures for Behavioral Experiments in Head-Fixed Mice

Abstract

The mouse is an increasingly prominent model for the analysis of mammalian neuronal circuits. Neural circuits ultimately have to be probed during behaviors that engage the circuits. Linking circuit dynamics to behavior requires precise control of sensory stimuli and measurement of body movements. Head-fixation has been used for behavioral research, particularly in non-human primates, to facilitate precise stimulus control, behavioral monitoring and neural recording. However, choice-based, perceptual decision tasks by head-fixed mice have only recently been introduced. Training mice relies on motivating mice using water restriction. Here we describe procedures for head-fixation, water restriction and behavioral training for head-fixed mice, with a focus on active, whisker-based tactile behaviors. In these experiments mice had restricted access to water (typically 1 ml/day). After ten days of water restriction, body weight stabilized at approximately 80% of initial weight. At that point mice were trained to discriminate sensory stimuli using operant conditioning. Head-fixed mice reported stimuli by licking in go/no-go tasks and also using a forced choice paradigm using a dual lickport. In some cases mice learned to discriminate sensory stimuli in a few trials within the first behavioral session. Delay epochs lasting a second or more were used to separate sensation (e.g. tactile exploration) and action (i.e. licking). Mice performed a variety of perceptual decision tasks with high performance for hundreds of trials per behavioral session. Up to four months of continuous water restriction showed no adverse health effects. Behavioral performance correlated with the degree of water restriction, supporting the importance of controlling access to water. These behavioral paradigms can be combined with cellular resolution imaging, random access photostimulation, and whole cell recordings.

Robust neuronal dynamics in premotor cortex during motor planning

“…On other days, mice were tested in experimental sessions lasting 1 to 2 hours where they received all their water (range, 0.5 to 2 mL). If mice did not maintain a stable body weight, they received supplementary water 48 . All surgical procedures were carried out aseptically under 1-2 % isofluorane anesthesia.…”

“…A layer of cyanoacrylate adhesive (Krazy glue, Elmer's Products Inc) was directly applied to the intact skull. A custom made headpost 48 was placed on the skull with its anterior edge aligned with the suture lambda (approximately over cerebellum) and cemented in place with clear dental acrylic (Lang Dental Jet Repair Acrylic; Part# 1223-clear). A thin layer of clear dental acrylic was applied over the cyanoacrylate adhesive covering the entire exposed skull, followed by a thin layer of clear nail polish (Electron Microscopy Sciences, Part# 72180).…”

“…The behavioral task and training have been described 3,48 . The stimulus was a metal pin (0.9 mm in diameter), presented at one of two possible positions (Fig.…”

Chronic imaging of movement-related Purkinje cell calcium activity in awake behaving mice

“…In addition, the olivo-cerebellar system may play a more general role in organizing motor control through temporal pattern generation (Jacobson et al 2008). Merging these findings into an improved model of cerebellar function will require a more detailed exploration of movement behavior in animals likely requiring new methodological approaches for functional evaluation of cerebellar circuits, for example, using trained mice to perform skilled licking or whisking movements for a water reward while under restricted water intake (e.g., Guo et al 2014).…”

MATLAB-based automated patch-clamp system for awake behaving mice

“…Not only do mice have well-established advantages for cellular and molecular neurobiology, such as transgenic methods for identifying and manipulating specific cell populations, but also they have a rich behavioral repertoire that includes sensory, motor, and cognitive aspects (Guo et al 2014). Moreover, recent experiments indicate that this behavioral repertoire is only partly diminished when mice are subjected to head fixation.…”