Operant Procedures for Assessing Behavioral Flexibility in Rats

Abstract

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one's environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer's disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

Adolescent binge ethanol exposure alters specific forebrain cholinergic cell populations and leads to selective functional deficits in the prefrontal cortex

“…Testing parameters were adapted from (Brady and Floresco, 2015), with 11 operant chambers (30 cm × 33 cm × 23 cm; Med Associates Inc., St. Albans, VT) located inside sound-attenuating boxes (59 cm × 55 cm × 36 cm). Each box was outfitted with a fan in order to provide white noise.…”

Persistent cognitive and morphological alterations induced by repeated exposure of adolescent rats to the abused inhalant toluene

“…Subjects were monitored to ensure both rats sampled the SCM. Lever press training was subsequently conducted in operant chambers (Med Associates, St. Albans, VT) that began during adulthood (P60) and proceeded as described previously (Brady & Floresco, 2015). Briefly, rats were first trained to lever press on a fixed-ratio (FR) 1 schedule for 45 µl SCM dispensed from a central feeding well over the course of three phases (1–3).…”

“…If the extended lever was not pressed during a trial, it was retracted and the house light was illuminated for a 30 s time out period which was recorded as an “omission”. Once a subject reached criteria (10 or fewer omissions per session for two consecutive days) a side preference test was performed as previously described (Brady & Floresco, 2015; Floresco, Block, & Tse, 2008). For each of 60 trials, both levers extended simultaneously and were reinforced on an FR1 schedule.…”

“…left vs right lever) now delivered the reward irrespective of the position of the visual cue (Brady & Floresco, 2015). We chose to use this visual cue-response shift because our primary interest was in ascertaining how toluene exposure may affect PFC functioning, and previous studies have shown that performance on this type of shift is more sensitive to disruption following PFC inactivation (Floresco et al, 2008).…”

“…Once rats achieved criterion performance (8 consecutive correct lever presses under 30 trials for two days in a row) on the strategy shift task, the response discrimination was reversed so that responses on the previously incorrect lever were now reinforced, as described previously (Brady & Floresco, 2015). Again, the visual cue lights were illuminated above one of the levers on each trial, but here, they served as distractors.…”