Probing Cortical Activity During Head-Fixed Behavior

Abstract

The cortex is crucial for many behaviors, ranging from sensory-based behaviors to working memory and social behaviors. To gain an in-depth understanding of the contribution to these behaviors, cellular and sub-cellular recordings from both individual and populations of cortical neurons are vital. However, techniques allowing such recordings, such as two-photon imaging and whole-cell electrophysiology, require absolute stability of the head, a requirement not often fulfilled in freely moving animals. Here, we review and compare behavioral paradigms that have been developed and adapted for the head-fixed preparation, which together offer the needed stability for live recordings of neural activity in behaving animals. We also review how the head-fixed preparation has been used to explore the function of primary sensory cortices, posterior parietal cortex (PPC) and anterior lateral motor (ALM) cortex in sensory-based behavioral tasks, while also discussing the considerations of performing such recordings. Overall, this review highlights the head-fixed preparation as allowing in-depth investigation into the neural activity underlying behaviors by providing highly controllable settings for precise stimuli presentation which can be combined with behavioral paradigms ranging from simple sensory detection tasks to complex, cross-modal, memory-guided decision-making tasks.

Keywords: 2AFC; Go/NoGo; anterior lateral motor cortex; cortex; head-fixed; posterior parietal cortex; primary sensory cortices; sensory-based behavior.

Figure 1

Head-fixed behavioral paradigms. (A) Schematic of the Go/NoGo task often referred to as a detection task. The animal should only respond upon detecting the stimulus. (B) Schematic of the Go/NoGo task involving discrimination of two stimuli. The animal should only respond to the Go-stimulus. This task is often referred to as a discrimination task. (C) Schematic of the two-alternative forced-choice (2AFC) task. Similar to (B), this task requires the discrimination between two different stimuli however, to eliminate pseudo responses, the animal must respond to both stimuli, for example by either licking left or licking right. (D) Schematic of the Go/NoGo discrimination task with delay. This task differs from (B) by having a delay separating the stimulus and the response. (E) Schematic of the Nonmatch to Sample Working memory task, based on the Go/NoGo discrimination paradigm. In this task, the animal is presented with two consecutive stimuli, separated by a delay. The animal must compare the two stimuli and respond accordingly.

Figure 2

Cortical activity during a delay 2AFC task. (A) Schematic of a whisker-mediated object localization 2AFC task. Modified from O’Connor et al. (2010a,b), Guo et al. (2014b) and Chen et al. (2017). (B) The primary somatosensory cortex (S1) has maximal influence during stimulus presentation (Guo et al., 2014b). (C) Anterior lateral motor cortex (ALM) ramps activity during the delay epoch and reaches a maximum during the response epoch (Guo et al., ; Li et al., ; Inagaki et al., 2018). (D) The posterior parietal cortex (PPC) is active throughout the 2AFC task, especially the stimulus and response epochs (Harvey et al., ; Goard et al., 2016).