Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Bussey, Timothy

2nd Supervisor

Saksida, Lisa

Joint Supervisor

Abstract

Habits enable animals to efficiently navigate their surroundings while tending to more cognitively demanding environmental factors. One mechanism underlying habit is known as stimulus-response (S-R) learning, which takes place in the dorsolateral striatum (DLS). However, there is limited knowledge regarding the complex striatal microcircuits involved in S-R learning and cognitive flexibility. Recently, attention has turned toward the GABAergic Parvalbumin-expressing (PV) interneurons that can modulate striatal outputs. Here, we utilized chemogenetic techniques and touchscreen cognitive assessments to analyze the influence of PV neurons on S-R learning in mice. When PV neurons were inhibited, during the acquisition of a S-R and cognitive flexibility cognitive assessment, there were no significant differences in the percent accuracy. Further exploratory analysis, however, revealed a significant difference in the male mice but not the female mice between the experimental groups for the acquisition of the S-R task. Furthermore, PV neuron inhibition did not affect performance of a previously acquired S-R task. These findings contribute to our understanding of what mechanisms are and are not necessary for the various cognitive functions in which the dorsal striatum is involved.

Summary for Lay Audience

Habit formation is a critical part of the everyday lives of animals, including humans. It allows animals to reduce cognitive effort to allow interaction with environmental cues that require immediate attention. One proposed mechanism underlying habit is known as stimulus-response learning, which is thought to be mediated by a specific part of the rodent brain called the dorsolateral striatum (DLS). Through repetition, associations made between environmental cues and responses (stimulus-response associations) are strengthened in the DLS. This causes the behavioural response to become solely dependent on the specific environmental cue. Cognitive flexibility is of equal importance and refers to the ability of animals to adapt to changes in associations between environmental cues. While extensive research has been conducted on the DLS’s contribution to these types of learning, there is less knowledge concerning the complex interactions between different groups of neurons (brain cells) within the DLS. Specifically, attention has turned towards a population of neurons called Parvalbumin-expressing (PV) interneurons. These cells can strongly control and reduce the activity of other brain cells within the DLS. Ultimately, they help in adjusting and regulating the overall activity of the striatum and contribute to its normal functioning. Thus, there is a need to explore the role that PV neurons play in stimulus-response learning and cognitive flexibility. In this current study, we aimed to understand whether PV neurons are necessary for the expression and acquisition of stimulus-response learning and for cognitive flexibility. To do this, we combined the use of touchscreen cognitive assessments with a technique called chemogenetics to precisely manipulate these interneurons in freely behaving mice. We found that the silencing of PV neurons did not impair the acquisition of a stimulus-response and cognitive flexibility task. However, an exploratory analysis found a significant difference in the percent accuracy of the male mice but not the female mice between the experimental groups during stimulus-response acquisition. Furthermore, silencing did not impair the performance of the previously learned stimulus-response task. These findings highlight the significance of delving deeper into the differences between males and females in the striatum and continuing research to unravel the complex neural connections within the DLS.

Creative Commons License

Creative Commons Attribution-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.

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