Abstract
In order to parse the causal elements underlying complex behaviors and decision-making processes, appropriate behavioral methods must be developed and used in concurrence with molecular, pharmacological, and electrophysiological approaches. Presented is a protocol for a novel Go/No-Go behavioral paradigm to study the brain attention and motivation/reward circuitry in awake, head-restrained rodents. This experimental setup allows: (1) Pharmacological and viral manipulation of various brain regions via targeted guide cannula; (2) Optogenetic cell-type specific activation and silencing with simultaneous electrophysiological recording and; (3) Repeated electrophysiological single and multiple unit recordings during ongoing behavior. The task consists of three components. The subject first makes an observing response by initiating a trial by lever pressing in response to distinctive Go or No-Go tones. Then, after a variable delay period, the subject is presented with a challenge period cued by white noise during which they must respond with a lever press for the Go condition or withhold from lever pressing for the duration of the cue in the No-Go condition. After correctly responding during the challenge period (Challenge) and a brief delay, a final reward tone of the same frequency as the initiation tone is presented and sucrose reward delivery is available and contingent upon lever pressing. Here, we provide a novel procedure and validating data set that allows researchers to study and manipulate components of behavior such as attention, motivation, impulsivity, and reward-related working memory during an ongoing operant behavioral task while limiting interference from non task-related behaviors.
Highlights
The use of operant behavioral tasks that utilize the head-immobilized condition in rodents have some advantages over tasks that occur under freely moving conditions by limiting the range of possible non task-relevant behaviors and distractors
Despite a growing number of studies that utilize head-fixed rodents, very few experiments have assessed psychological and physiological processes simultaneously occurring during operant behavioral tasks that require intentional skilled movements as conditional responses in the awake, head-restrained rodent[1,2]
Impulsivity and motivational deficits are complex behavioral phenotypes implicated in a number of psychiatric disorders including attention deficit hyperactivity disorder (ADHD), mania and depression associated with bipolar disorder, schizophrenia, pathological gambling, borderline personality disorder, and substance abuse[3]
Summary
The use of operant behavioral tasks that utilize the head-immobilized condition in rodents have some advantages over tasks that occur under freely moving conditions by limiting the range of possible non task-relevant behaviors and distractors. Head immobilization is a traditional and common method in electrophysiological studies utilizing behaving monkeys, in which skilled intentional forelimb movements (e.g. grasping) are widely used as conditional responses. Despite a growing number of studies that utilize head-fixed rodents, very few experiments have assessed psychological and physiological processes simultaneously occurring during operant behavioral tasks that require intentional skilled movements (e.g. lever pressing) as conditional responses in the awake, head-restrained rodent[1,2]. Variations of the Go/No-go task have long been applied to electrophysiological, lesion and pharmacological studies[4,5,6,7] This type of behavioral task has a high level of construct validity and clinical utility when studying the brain motivation/reward pathways and behaviors such as impulsivity. Impulsivity and motivational deficits are complex behavioral phenotypes implicated in a number of psychiatric disorders including attention deficit hyperactivity disorder (ADHD), mania and depression associated with bipolar disorder, schizophrenia, pathological gambling, borderline personality disorder, and substance abuse[3]
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