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Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2025)

Detecting and responding to emotionally salient stimuli is essential for adaptive behavior. The ventral hippocampus (vHPC) has been implicated in the evaluation of environmental threats and rewards, but the mechanisms by which upstream input modulates hippocampal encoding of salience remain incompletely understood. In this dissertation, I investigated the circuit architecture, input modulation, and neural dynamics that confer salience processing within the vHPC. Across five chapters, I work to define the organizational principles and functional role of these circuits in regulating emotionally charged behaviors.

In the first set of studies, I used high-throughput projection mapping techniques, retrograde tracing, and transcriptome profiling to define the molecular and anatomical organization of vHPC projection neurons. These experiments revealed that the majority of vHPC neurons are segregated into distinct projection-defined subpopulations that target limbic structures with a significant proportion of broadcasting neurons that collateralize to multiple areas especially the lateral septum. Furthermore, I identified several biased upstream inputs onto specific vHPC neurons and differential gene expression suggesting vHPC neurons form defined cell types beyond projection target.

Building on this framework, I next explored the role of a biased input from the thalamus in shaping vHPC activity. Using 1- and 2-photon in vivo calcium imaging during behavior, combined with chemogenetic inhibition of paraventricular thalamus (PVT) projections to vHPC, I found that thalamic input dynamically modulates the encoding of salient stimuli. Disrupting PVT→vHPC (PVTvHPC) communication impaired both behavioral discrimination and the emergence of salience-specific neural representations, highlighting a critical role for thalamic afferents in guiding hippocampal salience processing.Together, these findings support a model in which ventral hippocampal output neurons are organized into discrete, projection-specific modules, and salience representations within these modules are actively gated by dynamic thalamic input. These results revise classical circuit models of hippocampal function and suggest new mechanistic frameworks for understanding the neural basis of anxiety, depression, and other disorders of maladaptive salience evaluation.

    Cover page: Thalamus gates the coding of salient experiences in the hippocampus.
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2025)
    Anhedonia, the diminished drive to seek, value, and learn about rewards, is a core feature of major depressive disorder1-3. The neural underpinnings of anhedonia and how this emotional state drives behaviour remain unclear. Here we investigated the neural code of anhedonia by taking advantage of the fact that when mice are exposed to traumatic social stress, susceptible animals become socially withdrawn and anhedonic, whereas others remain resilient. By performing high-density electrophysiology to record neural activity patterns in the basolateral amygdala (BLA) and ventral CA1 (vCA1), we identified neural signatures of susceptibility and resilience. When mice actively sought rewards, BLA activity in resilient mice showed robust discrimination between reward choices. By contrast, susceptible mice exhibited a rumination-like signature, in which BLA neurons encoded the intention to switch or stay on a previously chosen reward. Manipulation of vCA1 inputs to the BLA in susceptible mice rescued dysfunctional neural dynamics, amplified dynamics associated with resilience, and reversed anhedonic behaviour. Finally, when animals were at rest, the spontaneous BLA activity of susceptible mice showed a greater number of distinct neural population states. This spontaneous activity allowed us to decode group identity and to infer whether a mouse had a history of stress better than behavioural outcomes alone. This work reveals population-level neural dynamics that explain individual differences in responses to traumatic stress, and suggests that modulating vCA1-BLA inputs can enhance resilience by regulating these dynamics.
      Cover page: Understanding the neural code of stress to control anhedoniaCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2020)
      The ventral hippocampus (vHPC) is a critical hub in networks that process emotional information. While recent studies have indicated that ventral CA1 (vCA1) projection neurons are functionally dissociable, the basic principles of how the inputs and outputs of vCA1 are organized remain unclear. Here, we used viral and sequencing approaches to define the logic of the extended vCA1 circuit. Using high-throughput sequencing of genetically barcoded neurons (MAPseq) to map the axonal projections of thousands of vCA1 neurons, we identify a population of neurons that simultaneously broadcast information to multiple areas known to regulate the stress axis and approach-avoidance behavior. Through molecular profiling and viral input-output tracing of vCA1 projection neurons, we show how neurons with distinct projection targets may differ in their inputs and transcriptional signatures. These studies reveal new organizational principles of vCA1 that may underlie its functional heterogeneity.
        Cover page: Circuit and molecular architecture of a ventral hippocampal network
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