Connecting the Dots: Integrating Visual Projections, Observational Learning, and Behavior Representation in Rodent Prefrontal Cortices
Doctoral thesis
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https://hdl.handle.net/11250/3115057Utgivelsesdato
2024Metadata
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Sammendrag
The medial prefrontal cortex (mPFC) has been studied extensively across species, across functions and across experimental paradigms. Despite this, we still have not fully elucidated what this brain area truly does and how, especially in naturalistic, non-restrained environments. There is consensus in the field that the medial prefrontal area is important for behavioral flexibility and contextually appropriate action selection. For a brain area to successfully perform these kinds of computations, a vast range of cognitive functions must be utilized and different sensory information streams must be integrated into a coherent representation of the current context. This includes representations of ongoing behaviors, so that necessary adjustments can be made based on sensory feedback and changes in one’s internal state. The work in this thesis reflects an effort to understand how the mPFC is able to integrate these disparate computations successfully. In doing so, the work here gives insights into a possible anatomical pathway by which visual signals reach frontal cortices in mice, demonstrates a social learning paradigm that likely depends on such a pathway, as well as showing that the actual neural representation of behavior dynamically changes in freely moving rats.
A visuomotor pathway important for enabling proper interaction with objects in one’s spatial surroundings is known as the “dorsal stream” of visual processing. This concept is introduced in the first paper, and the work I present characterizes anatomical connections in this pathway in mice in greater detail than previous studies. The study investigated the intersection of primary visual cortex (V1) output fibers onto secondary motor cortex (M2)-projecting neurons in the extrastriate cortex of mice. Utilizing high resolution analyses on 3D reconstructed cellular data, we confirmed that visual and motor pathways overlap in extrastriate cortex, primarily in the anterior and medial extrastriate areas. This confirms previous findings of such a pathway between visual and motor areas. As these areas also project to other prefrontal areas, this pathway constitutes a possible anatomical pathway supporting visuomotor behavior and may inform cognitive processes, like during social interactions, including observational learning. The prefrontal areas are hypothesized to be important for observational learning based on their involvement in various aspects of social cognition, as well as their extensive connections with sensory, motor, and cognitive areas.
My second study investigated observational learning, for which I developed a paradigm that does not rely on fear, aversive stimuli or food deprivation to motivate the learning of a task. The field has been lacking such a paradigm that would enable mechanistic investigations of pathways other than cortico-limbic ones in social fear learning, or how the process of observational learning is represented in the brain when animals are not under stress. In the paradigm, using intracranial stimulation as a reinforcer, observer animals are able to learn a 2-step behavioral sequence purely through observation of well-trained demonstrators after only three days of observation. The observer animals outperformed control animals during testing, indicating successful observational learning. However, a subgroup of animals did not learn the task. Hence, I suggest adjustments for future iterations of the protocol in the hopes that my work has laid a solid foundation for a non-fear based observational learning paradigm.
As the mPFC has been shown to support social cognition in addition to a host of other behaviorally relevant functions, my third study used an unbiased approach to analyze neural data in freely moving rats across different behavioral contexts. As most studies of prefrontal areas have been done in well-defined and tightly controlled experimental paradigms on isolated cognitive features, I wanted to break with tradition and characterize neural dynamics in the mPFC in relation to naturalistic behavior itself, that could explain and tie the different findings together. To do so, I wanted animals to be allowed to move freely in different contexts that would prompt them to exhibit a range of naturalistic and spontaneous behaviors, like animals do outside a strictly task-based context. I was able to show that the mPFC carries neural representations at the population level for different behavioral states that evolve dynamically as the animal engages with its environment, potentially recruiting single neurons into meaningful ensembles depending on the momentary needs and motivations of the animal. Physical features and kinematics did not account for the entirety of the behavioral representations, indicating that the internal state of the animal, cognitive processes and/or sensory input from the environment might also contribute. Thus, I show that the mPFC encodes flexible behaviors necessary for solving ecologically relevant tasks, and I use this study as a backdrop to discuss the importance of both well-controlled and naturalistic experiments for a comprehensive understanding of the function of the brain.
Består av
Paper 1: Hovde, Karoline; Rautio, Ida Välikangas; Hegstad, Andrea Marie; Witter, Menno Peter; Whitlock, Jonathan Robert. Visuomotor interactions in the mouse forebrain mediated by extrastriate cortico-cortical pathways. Frontiers in Neuroanatomy 2023 ;Volum 17. s. – Published by Frontiers Media. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Available at: http://dx.doi.org/10.3389/fnana.2023.1188808Paper 2: Rautio, Ida Välikangas; Holmberg, Ella Holt; Kurup, Devika; Dunn, Benjamin Adric; Whitlock, Jonathan Robert. A novel paradigm for observational learning in rats. Cognitive Neurodynamics 2023 s. – Published by Springer. This article is licensed under a Creative Commons Attribution 4.0 International License CC BY. Available at: http://dx.doi.org/10.1007/s11571-023-10022-8
Paper 3: Rautio, Ida Välikangas; Nevjen, Fredrik; Hem, Ingeborg; Dunn, Benjamin Adric; Whitlock, Jonathan Robert. Behavior-state representation in the rat medial prefrontal cortex. This paper will be submitted for publication and is therefore not included.