James D. Rowan’s research while affiliated with Wesleyan College and other places

Recombinant DNA technology has facilitated animal models that could be used to investigate candidate gene contributions to acquisition and retention. In practice, researchers focus on genetics or simple behaviors, rarely combining both or investigating genetic contributions to complex behaviors. We investigated inbred C57BL/6 and outbred CF1 mice’s ability to perform single-alternation and double-alternation patterns. C57BL/6 mice performed better, especially on double-alternation patterns. We also observed sex differences in the inbred C57BL/6 strain for the double alternation pattern. This suggests paradigms for investigating complex behaviors can be useful in uncovering strain differences and contributions of candidate genes to learning, retention, and performance.

Many organisms show aptitude for learning and performing patterned sequences. However, we do not yet have a complete account of how they accomplish this. One of the most successful is Restle’s hierarchical model, which supposes organisms represent sequences using the simplest form available through using hierarchies to organize the sequences’ elements. In two experiments, we evaluated if Restle’s model accurately accounted for rats’ patterned sequence learning. First, we compared rats’ learning of a runs pattern with three levels of hierarchical organization with no violations of pattern structure to learning of the same pattern with one violation of pattern structure in the pattern’s second half. Restle’s model predicts rats should have more difficulty learning the violation pattern and that rats learning the pattern with the violation in the second half of the pattern should attempt to reflect that violation to the first half. The results indicated that rats had more difficulty learning the violation pattern and that inserting a violation in the second half of the pattern led rats to make significantly more errors on the second half of the pattern relative to the first half of the pattern. Rats did not insert the violation from the second half of the pattern into the first half of the pattern. In a second experiment, we continued to explore if Restle’s model accurately accounted for rats’ pattern learning using more complex patterns. The present results of both experiments and prior work with humans were inconsistent with Restle’s model, suggesting more work is needed to develop a model that accurately accounts for rats’ learning of complex patterned sequences.

Numerous investigators have examined the hypothesis that males and females learn or perform differentially on various tasks. However, many of the behavioural investigations with nonhuman animals (e.g., rats) have used paradigms that do not permit the exploration of complex learning and memory between the sexes. To this end, we explored the ability of male versus female mice to learn three different patterns in succession in three separate experiments: single alternation (e.g., right, left, right, left), double alternation (e.g., right, right, left, left), and runs (e.g., 123, 234, 345, 456, 567, 678, 781, 812, where digits represent locations within a circular array in the counterclockwise direction). We hypothesized that sex differences, if they existed, would be most likely to appear as the pattern to be learned became more complex (required more rules to capture how elements relate to one another). The results indicated that mice can learn all three pattern types, but learning was more difficult as pattern complexity increased. Males learned the runs pattern significantly more quickly than females did; no significant differences were found between males and females for acquisition of the single-alternation or double-alternation patterns. These results suggest that sex differences in serial pattern learning within rodents are not unique to rats and are more likely to be seen during acquisition of more complex patterns.

The effects of chronic adolescent fluoxetine (FLX, Prozac®) exposure on adult cognition are largely unknown. We used a serial multiple choice (SMC) task to characterize the effects of adolescent FLX exposure on rat serial pattern learning in adulthood. Male rats were exposed to either 1.0, 2.0, or 4.0 mg/kg/day FLX for five consecutive days each week for five weeks during adolescence, followed by a 35-day drug-free period. As adults, the rats were trained in a task that required them to learn a highly structured sequential pattern of responses in an octagonal chamber for water reinforcement. In a transfer phase, the terminal element of the pattern was replaced by a violation element that was inconsistent with previously learned pattern structure. Results indicated that adolescent FLX exposure caused differential learning deficits for different types of elements in the serial pattern. Adolescent exposure to 1.0 or 4.0 mg/kg/day FLX, but not 2.0 mg/kg/day FLX, impaired chunk-boundary element learning, which is known to be mediated by stimulus-response (S-R) learning. All three doses of FLX impaired violation element learning, which is known to be mediated by multiple-cue learning. FLX did not impair within-chunk element learning, which is known to be mediated by rule-learning mechanisms. The results indicate that adolescent FLX exposure produced multiple cognitive impairments that were detectable in adulthood long after drug exposure ended.

Researchers investigating how organisms learn patterns of information have dedicated much attention to determining how sequences that can be meaningfully organized are parsed during learning. Results have indicated that cues, often termed phrasing cues, from many domains, including visual, auditory, temporal, and spatial, can influence how patterns of information are interpreted and learned. For example, the sequence of numbers 123234345456 is made easier to learn when the cues imposed by experimenters (here, spaces) match the transitions between groups of related elements (i.e., chunks) in the sequence (i.e., 123 234 345 456). When such cues do not match the natural transitions of the pattern between chunks (i.e., 12 323 43 45 456), performance is not facilitated and instead is often hindered. Additionally, the placement of such cues can affect how the same sequence is encoded (i.e., runs: …234 345 456… vs. trills: …232 343 454…). Through four experiments, we explored the effect of incorporating responses as spatial phrasing cues on humans’ and rats’ pattern production. The results indicated that the spatial phrasing cues were interpreted as phrasing cues rather than as part of the structure of the pattern and that they facilitated performance when placed congruent to the natural structure of the sequence. Additionally, rats and humans appeared to use their own responses as phrasing cues.

The long-term effects of adolescent exposure to methylphenidate (MPD) on adult cognitive capacity are largely unknown. We utilized a serial multiple choice (SMC) task, which is a sequential learning paradigm for studying complex learning, to observe the effects of methylphenidate exposure during adolescence on later serial pattern acquisition during adulthood. Following 20.0mg/kg/day MPD or saline exposure for 5days/week for 5weeks during adolescence, male rats were trained to produce a highly structured serial response pattern in an octagonal operant chamber for water reinforcement as adults. During a transfer phase, a violation to the previously-learned pattern structure was introduced as the last element of the sequential pattern. Results indicated that while rats in both groups were able to learn the training and transfer patterns, adolescent exposure to MPD impaired learning for some aspects of pattern learning in the training phase which are learned using discrimination learning or serial position learning. In contrast adolescent exposure to MPD had no effect on other aspects of pattern learning which have been shown to tap into rule learning mechanisms. Additionally, adolescent MPD exposure impaired learning for the violation element in the transfer phase. This indicates a deficit in multi-item learning previously shown to be responsible for violation element learning. Thus, these results clearly show that adolescent MPD produced multiple cognitive impairments in male rats that persisted into adulthood long after MPD exposure ended. Copyright © 2015. Published by Elsevier Inc.

Many have investigated how organisms detect and learn about the patterned sequences of stimuli that they regularly encounter. In some cases, a sequence of stimuli may be structurally ambiguous. That is, more than one rule might be generated in attempts to describe or organize the sequence in a meaningful way. Past studies exploring learning of such sequences have indicated that while subjects can learn about the rules describing such sequences, they often make errors in learning consistent with holding multiple representations of the sequence. Here, we examined the ability of humans and rats to perform runs and trills sequences over the same spatial locations in a pattern production task using a touchscreen (humans) or a circular operant chamber array (rats). One of two signals, presented immediately prior to the start of each trial, indicated which sequence to perform. The results indicated that both species were able to learn to produce runs and trills sequences at levels exceeding chance, which provides additional evidence that humans and rats may hold multiple representations of structurally ambiguous sequences.

Two experiments examined whether muscarinic cholinergic systems play a role in rats' ability to perform well-learned highly-structured serial response patterns, particularly focusing on rats' performance on pattern elements learned by encoding rules versus by acquisition of stimulus-response (S-R) associations. Rats performed serial patterns of responses in a serial multiple choice task in an 8-lever circular array for hypothalamic brain-stimulation reward. Two experiments examined the effects of atropine, a centrally-acting muscarinic cholinergic receptor antagonist, on rats' ability to perform pattern elements where responses were controlled by rules versus elements, such as rule-inconsistent "violation elements" and elements following "phrasing cues," where responses were controlled by associative cues. In Experiment 1, 3-element chunks of both patterns were signaled by pauses that served as phrasing cues before chunk-boundary elements, but one pattern also included a violation element that was inconsistent with pattern structure. Once rats reached a high criterion of performance, the drug challenge was intraperitoneal injection of a single dose of 50 mg/kg atropine sulfate. Atropine impaired performance on elements learned by S-R learning, namely, chunk-boundary elements and the violation element, but had no effect on performance of rule-based within-chunk elements. In Experiment 2, patterns were phrased and unphrased perfect patterns (i.e., without violation elements). To control for peripheral effects of atropine, rats were treated with a series of doses of either centrally-acting atropine or peripherally-acting atropine methyl nitrate (AMN), which does not cross the blood-brain barrier. Once rats reached a high criterion, the drug challenges were on alternate days in the order 50, 25, and 100 mg/kg of either atropine sulfate or AMN. Atropine, but not AMN, impaired performance in the phrased perfect pattern for pattern elements where S-R associations were important for performance, namely, chunk-boundary elements. However, in the structurally more ambiguous unphrased perfect pattern where rats had fewer cues and presumably relied more on S-R associations throughout, atropine impaired performance on all pattern elements. Thus, intact muscarinic cholinergic systems were shown to be necessary for discriminative control previously established by S-R learning, but were not necessary for rule-based serial pattern performance.

This study was designed to determine whether deficits in adult serial pattern learning caused by adolescent nicotine exposure persist as impairments in asymptotic performance, whether adolescent nicotine exposure differentially retards learning about pattern elements that are inconsistent with "perfect" pattern structure, and whether there are sex differences in rats' response to adolescent nicotine exposure as assessed by a serial multiple choice task. The current study replicated the results of our initial report (Fountain, Rowan, Kelley, Willey, & Nolley, 2008) using this task by showing that adolescent nicotine exposure (1.0mg/kg/day nicotine for 35days) produced a specific cognitive impairment in male rats that persisted into adulthood at least a month after adolescent nicotine exposure ended. In addition, sex differences were observed even in controls, with additional evidence that adolescent nicotine exposure significantly impaired learning relative to same-sex controls for chunk boundary elements in males and for violation elements in females. All nicotine-induced impairments were overcome by additional training so that groups did not differ at asymptote. An examination of the types of errors rats made indicated that adolescent nicotine exposure slowed learning without affecting rats' cognitive strategy in the task. This data pattern suggests that exposure to nicotine in adolescence may have impaired different aspects of adult stimulus-response discrimination learning processes in males and females, but left abstract rule learning processes relatively spared in both sexes. These effects converge with other findings in the field and reinforce the concern that adolescent nicotine exposure poses an important threat to cognitive capacity in adulthood.