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Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2013)

Locomotion is a behavior essential for survival. It is important for guiding goal-directed approach towards desired outcomes and avoidance of aversive stimuli. To this end, a large number of processes in the brain are both regulated by and serve to inform the locomotor behavior of animals. Here, we attempt to define the neural circuits underlying locomotor control, the associated changes that locomotion has upon brain states, and the neurobiological basis of locomotor decisions. In Chapter 1, we describe what is known regarding the neural circuits guiding locomotor behaviors. We provide background also regarding the known mechanisms that guide changes in brain states and are associated with locomotion. We then touch upon recent literature attempting to understand how information is used to guide decision-making to better understand the specific problem of how locomotor decisions are made. In Chapter 2, we then present novel findings, identifying brainstem circuits that control locomotion and concurrently regulate visual processing of information in the cortex through the basal forebrain. These findings may apply to other networks beyond the visual system and form a general mechanism by which various brain regions are modulated by behavioral state. In Chapter 3, we demonstrate that these brainstem circuits are under the regulation of the basal ganglia. These studies identify a conserved, phylogenetically ancient pathway for guiding locomotion that may exist in all vertebrates and represent one of the earliest functions of the basal ganglia system. In chapter 4, we leverage our understanding of the basal ganglia pathways for locomotor control to understand the processes of goal-directed decision-making. In chapter 5, we find that the ventral striatal shares a parallel organization to the dorsal striatum for implementing reinforcement learning to guide future locomotor decision-making. These studies into the basis of goal-directed locomotor behaviors may elucidate general principles for decision-making. Collectively, these results demonstrate control systems for locomotion are deeply interconnected with a diverse array of processes throughout the brain that guide goal-directed locomotor behaviors.

    Cover page: Neural Circuit for Locomotor Control, Brain State Regulation, and Decision-Making
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2015)
    Decision making can be defined as the flexible integration and transformation of information from the external world into action. Recently, the development of novel genetic tools and new behavioral paradigms has made it attractive to study behavior of all kinds in rodents. By some perspectives, rodents are not an acceptable model for the study of decision making due to their simpler behavior often attributed to their less extensive cortical development when compared to non-human primates. We argue that decision making can be approached with a common framework across species. We review insights from comparative anatomy that suggest the expansion of cortical-striatal connectivity is a key development in evolutionary increases in behavioral flexibility. We briefly review studies that establish a role for corticostriatal circuits in integrative decision making. Finally, we provide an overview of a few recent, highly complementary rodent decision making studies using genetic tools, revealing with new cellular and temporal resolution how, when and where information can be integrated and compared in striatal circuits to influence choice.
      Cover page: Between the primate and ‘reptilian’ brain: Rodent models demonstrate the role of corticostriatal circuits in decision making
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2016)
      The basal ganglia (BG) are critical for adaptive motor control, but the circuit principles underlying their pathway-specific modulation of target regions are not well understood. Here, we dissect the mechanisms underlying BG direct and indirect pathway-mediated control of the mesencephalic locomotor region (MLR), a brainstem target of BG that is critical for locomotion. We optogenetically dissect the locomotor function of the three neurochemically distinct cell types within the MLR: glutamatergic, GABAergic, and cholinergic neurons. We find that the glutamatergic subpopulation encodes locomotor state and speed, is necessary and sufficient for locomotion, and is selectively innervated by BG. We further show activation and suppression, respectively, of MLR glutamatergic neurons by direct and indirect pathways, which is required for bidirectional control of locomotion by BG circuits. These findings provide a fundamental understanding of how BG can initiate or suppress a motor program through cell-type-specific regulation of neurons linked to specific actions.
        Cover page: Cell-Type-Specific Control of Brainstem Locomotor Circuits by Basal Ganglia.
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2014)
        Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion.
          Cover page: Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2012)
          In changing environments, animals must adaptively select actions to achieve their goals. In tasks involving goal-directed action selection, striatal neural activity has been shown to represent the value of competing actions. Striatal representations of action value could potentially bias responses toward actions of higher value. However, no study to date has demonstrated the direct effect of distinct striatal pathways in goal-directed action selection. We found that transient optogenetic stimulation of dorsal striatal dopamine D1 and D2 receptor-expressing neurons during decision-making in mice introduced opposing biases in the distribution of choices. The effect of stimulation on choice was dependent on recent reward history and mimicked an additive change in the action value. Although stimulation before and during movement initiation produced a robust bias in choice behavior, this bias was substantially diminished when stimulation was delayed after response initiation. Together, our data suggest that striatal activity is involved in goal-directed action selection.
            Cover page: Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2021)
            Vision is the primary sense humans use to evaluate and respond to threats. Understanding the biological underpinnings of the human threat response has been hindered by lack of realistic in-lab threat paradigms. We established an immersive virtual reality (VR) platform to simultaneously measure behavior, physiological state, and neural activity from the human brain using chronically implanted electrodes. Subjects with high anxiety showed increased visual scanning in response to threats as compared to healthy controls. In both healthy and anxious subjects, the amount of scanning behavior correlated with the magnitude of physiological arousal, suggesting that visual scanning behavior is directly linked to internal state. Intracranial electroencephalography (iEEG) recordings from three subjects suggested that high-frequency gamma activity in the insula positively correlates with physiological arousal induced by visual threats and that low-frequency theta activity in the orbitofrontal cortex (OFC) negatively correlates with physiological arousal induced by visual threats. These findings reveal a key role of eye movements and suggest that distinct insula and OFC activation dynamics may be important for detecting and adjusting human stress in response to visually perceived threats.
              Cover page: Human Responses to Visually Evoked Threat
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