A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments

Summary

A fully automated protocol for rodent operant conditioning is proposed. The protocol relies on precise temporal control of behavioral events to investigate the extent to which this control influences neural activity underlying sensorimotor integration and cognitive control experiments.

Abstract

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. Higher cognitive functions that require precise control over sensorimotor responses such as decision-making and attentional modulation, however, are typically assessed in nonhuman primates. Despite the richness of primate behavior that allows multiple variants of these functions to be studied, the rodent model remains an attractive, cost-effective alternative to primate models. Furthermore, the ability to fully automate operant conditioning in rodents adds unique advantages over the labor intensive training of nonhuman primates while studying a broad range of these complex functions.

Here, we introduce a protocol for operantly conditioning rats on performing working memory tasks. During critical epochs of the task, the protocol ensures that the animal's overt movement is minimized by requiring the animal to 'fixate' until a Go cue is delivered, akin to nonhuman primate experimental design. A simple two alternative forced choice task is implemented to demonstrate the performance. We discuss the application of this paradigm to other tasks.

Introduction

Studying the relation between neurophysiology and behavior is the ultimate goal in systems neuroscience. Historically, there has been a tradeoff between animal model choice and behavioral repertoire^1-5. While simple organisms like sea slugs⁶ or squids⁷ have been used extensively to study properties of single ion channels, neurons and simple neural circuits, higher order species are needed to study more complex functions such as spatial navigation, decision making^8-11 and cognitive control^12-14. Despite being a standard animal model for human like behavior, use of nonhuman primates prompts cost and ethical consider....

Protocol

All procedures involving animals were approved by the Michigan State University Institutional Animal Care and Use Committee (IACUC).

1. Experimental Setup

1. Use an operant conditioning box which consists of a five-hole nosepoke wall on one side and a food delivery trough on the opposite side.
   1. The center nosepoke hole is considered as a "fixation" hole and the four other holes (two on each side of the fixation hole) are considered motor target holes. Each hole is equipped with a tri-color LED and an infrared beam emitter-detector system that detects when the animal enters and retracts from the fixation hole.

Results

The suggested framework enables training the subject on a range of cognitive tasks. Here we implemented an instructed delay task designed to investigate the mechanisms of goal-directed actions in the rodent prefrontal cortex. Figure 1 shows a flowchart of the experimental design.

To ensure that the subject understands the task requirement at every step, performance measures should be continuously assessed. Figure 2 shows an example performance of one subject a.......

Discussion

Rats have been widely used in neuroscience research for over a century. Since Thorndike's introduction of the concept of the law of effect in cats³⁴, operant conditioning has been the standard approach to test different aspects of animal behavior. Many neuroscience experiments involving decision making and motor preparation include a delay period between the instruction cues and the action interval. It is desirable to minimize movements during these delay periods to reduce any confounds to the neural data .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
5-holed Nose Poke with 3 Stim Cue Light Rat Cage	Coulbourn	H21-06M/R
Test cage	Coulbourn	H10-11R-TC
Graphic State Software	Coulbourn
Programmable tone/noise generator	Coulbourn	A12-33
Dustless precision pellets	Bio-Serv	F0165
Speaker module	Coulbourn	H12-01R