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Open Access Publications from the University of California

Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2017)

The brain is constantly bombarded with sensory stimuli. In order to process and perceive such diverse information streams simultaneously, the brain prioritizes information relevant to an animal’s current behavioral needs. In this thesis, I investigate the neural mechanisms that enable the brain to increase or decrease visual signals depending on an animal’s behavioral state. In chapter 1, I illustrate a novel mechanism, 3-5 Hz membrane potential (Vm) oscillations, that decreases the responsiveness of neurons in the primary visual cortex (V1) of mice. Using 2-photon guided whole-cell recordings as mice passive viewed and actively engaged drifting sine-wave gratings, I discovered that these visually-evoked phenomena were not influenced by changes in arousal or animal movement, but their timing was influenced by an animal’s behavioral state. In addition to uncovering a novel mechanism for reducing the responsiveness of neurons in the brain, this chapter substantially furthers the field’s knowledge of how behavior and arousal affect the membrane potential of neurons in the cerebral cortex. In chapter 2, I develop a method to train animals how to perform a visual attention task. I describe the hardware and software tools used to actuate the task and the method used to train the animals. Using the method outlined in this chapter, I was able to routinely train animals to perform a multimodal attention task with approximately one month of training. In chapter 3, I employed this new attention model and, using 2-photon guided whole-cell recordings in behaving animals, I discovered that attention boosts the depolarization associated with visual stimulation in layer 2/3 V1 neurons, illustrating a potential mechanism that causes neurons to be more responsive to visual cues during attention. Finally, using 128 channel silicon nanoprobes chronically implanted in V1, I verified that the attention task increased the responsiveness of V1 neurons and desynchronized the local network in mice, replicating results previously obtained in non-human primate models and setting the groundwork for future study. As a result, my thesis details novel neural mechanisms for enhancing or dampening visual signals and expands our knowledge of how the brain prioritizes information according to an animal’s behavioral context.

    Cover page: Behavioral State Modulates Primary Visual Cortex Responsiveness in Mice
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2017)
    Low-frequency membrane potential (Vm) oscillations were once thought to only occur in sleeping and anesthetized states. Recently, low-frequency Vm oscillations have been described in inactive awake animals, but it is unclear whether they shape sensory processing in neurons and whether they occur during active awake behavioral states. To answer these questions, we performed two-photon guided whole-cell Vm recordings from primary visual cortex layer 2/3 excitatory and inhibitory neurons in awake mice during passive visual stimulation and performance of visual and auditory discrimination tasks. We recorded stereotyped 3-5 Hz Vm oscillations where the Vm baseline hyperpolarized as the Vm underwent high amplitude rhythmic fluctuations lasting 1-2 s in duration. When 3-5 Hz Vm oscillations coincided with visual cues, excitatory neuron responses to preferred cues were significantly reduced. Despite this disruption to sensory processing, visual cues were critical for evoking 3-5 Hz Vm oscillations when animals performed discrimination tasks and passively viewed drifting grating stimuli. Using pupillometry and animal locomotive speed as indicators of arousal, we found that 3-5 Hz oscillations were not restricted to unaroused states and that they occurred equally in aroused and unaroused states. Therefore, low-frequency Vm oscillations play a role in shaping sensory processing in visual cortical neurons, even during active wakefulness and decision making.SIGNIFICANCE STATEMENT A neuron's membrane potential (Vm) strongly shapes how information is processed in sensory cortices of awake animals. Yet, very little is known about how low-frequency Vm oscillations influence sensory processing and whether they occur in aroused awake animals. By performing two-photon guided whole-cell recordings from layer 2/3 excitatory and inhibitory neurons in the visual cortex of awake behaving animals, we found visually evoked stereotyped 3-5 Hz Vm oscillations that disrupt excitatory responsiveness to visual stimuli. Moreover, these oscillations occurred when animals were in high and low arousal states as measured by animal speed and pupillometry. These findings show, for the first time, that low-frequency Vm oscillations can significantly modulate sensory signal processing, even in awake active animals.
      Cover page: Visually Evoked 3–5 Hz Membrane Potential Oscillations Reduce the Responsiveness of Visual Cortex Neurons in Awake Behaving Mice
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2023)
      Effective task execution requires the representation of multiple task-related variables that determine how stimuli lead to correct responses. Even the primary visual cortex (V1) represents other task-related variables such as expectations, choice, and context. However, it is unclear how V1 can flexibly accommodate these variables without interfering with visual representations. We trained mice on a context-switching cross-modal decision task, where performance depends on inferring task context. We found that the context signal that emerged in V1 was behaviorally relevant as it strongly covaried with performance, independent from movement. Importantly, this signal was integrated into V1 representation by multiplexing visual and context signals into orthogonal subspaces. In addition, auditory and choice signals were also multiplexed as these signals were orthogonal to the context representation. Thus, multiplexing allows V1 to integrate visual inputs with other sensory modalities and cognitive variables to avoid interference with the visual representation while ensuring the maintenance of task-relevant variables.
        Cover page: Continuous multiplexed population representations of task context in the mouse primary visual cortex.
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2024)
        Attention supports decision making by selecting the features that are relevant for decisions. Selective enhancement of the relevant features and inhibition of distractors has been proposed as potential neural mechanisms driving this selection process. Yet, how attention operates when relevance cannot be directly determined, and the attention signal needs to be internally constructed is less understood. Here we recorded from populations of neurons in the anterior cingulate cortex (ACC) of mice in an attention-shifting task where relevance of stimulus modalities changed across blocks of trials. In contrast with V1 recordings, decoding of the irrelevant modality gradually declined in ACC after an initial transient. Our analytical proof and a recurrent neural network model of the task revealed mutually inhibiting connections that produced context-gated suppression as observed in mice. Using this RNN model we predicted a correlation between contextual modulation of individual neurons and their stimulus drive, which we confirmed in ACC but not in V1.
          Cover page: Shifts in attention drive context-dependent subspace encoding in anterior cingulate cortex in mice during decision making.
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