Professional Education

  • Bachelor of Arts, Williams College (2006)
  • Doctor of Philosophy, University of California San Francisco (2011)

Stanford Advisors

Journal Articles

  • Rapid and Continuous Modulation of Hippocampal Network State during Exploration of New Places PLOS ONE Kemere, C., Carr, M. F., Karlsson, M. P., Frank, L. M. 2013; 8 (9)


    Hippocampal information processing is often described as two-state, with a place cell state during movement and a reactivation state during stillness. Relatively little is known about how the network transitions between these different patterns of activity during exploration. Here we show that hippocampal network changes quickly and continuously as animals explore and become familiar with initially novel places. We measured the relationship between moment-by-moment changes in behavior and information flow through hippocampal output area CA1 in rats. We examined local field potential (LFP) patterns, evoked potentials and ensemble spiking and found evidence suggestive of a smooth transition from strong CA3 drive of CA1 activity at low speeds to entorhinal cortical drive of CA1 activity at higher speeds. These changes occurred with changes in behavior on a timescale of less than a second, suggesting a continuous modulation of information processing in the hippocampal circuit as a function of behavioral state.

    View details for DOI 10.1371/journal.pone.0073114

    View details for Web of Science ID 000324238400044

    View details for PubMedID 24023818

  • Hippocampal SWR Activity Predicts Correct Decisions during the Initial Learning of an Alternation Task NEURON Singer, A. C., Carr, M. F., Karlsson, M. P., Frank, L. M. 2013; 77 (6): 1163-1173


    The hippocampus frequently replays memories of past experiences during sharp-wave ripple (SWR) events. These events can represent spatial trajectories extending from the animal's current location to distant locations, suggesting a role in the evaluation of upcoming choices. While SWRs have been linked to learning and memory, the specific role of awake replay remains unclear. Here we show that there is greater coordinated neural activity during SWRs preceding correct, as compared to incorrect, trials in a spatial alternation task. As a result, the proportion of cell pairs coactive during SWRs was predictive of subsequent correct or incorrect responses on a trial-by-trial basis. This effect was seen specifically during early learning, when the hippocampus is essential for task performance. SWR activity preceding correct trials represented multiple trajectories that included both correct and incorrect options. These results suggest that reactivation during awake SWRs contributes to the evaluation of possible choices during memory-guided decision making.

    View details for DOI 10.1016/j.neuron.2013.01.027

    View details for Web of Science ID 000316645000016

    View details for PubMedID 23522050

  • Transient Slow Gamma Synchrony Underlies Hippocampal Memory Replay NEURON Carr, M. F., Karlsson, M. P., Frank, L. M. 2012; 75 (4): 700-713


    The replay of previously stored memories during hippocampal sharp wave ripples (SWRs) is thought to support both memory retrieval and consolidation in distributed hippocampal-neocortical circuits. Replay events consist of precisely timed sequences of spikes from CA3 and CA1 neurons that are coordinated both within and across hemispheres. The mechanism of this coordination is not understood. Here, we show that during SWRs in both awake and quiescent states there are transient increases in slow gamma (20-50 Hz) power and synchrony across dorsal CA3 and CA1 networks of both hemispheres. These gamma oscillations entrain CA3 and CA1 spiking. Moreover, during awake SWRs, higher levels of slow gamma synchrony are predictive of higher quality replay of past experiences. Our results indicate that CA3-CA1 gamma synchronization is a central component of awake memory replay and suggest that transient gamma synchronization serves as a clocking mechanism to enable coordinated memory reactivation across the hippocampal network.

    View details for DOI 10.1016/j.neuron.2012.06.014

    View details for Web of Science ID 000307914500017

    View details for PubMedID 22920260

  • A single microcircuit with multiple functions: state dependent information processing in the hippocampus CURRENT OPINION IN NEUROBIOLOGY Carr, M. F., Frank, L. M. 2012; 22 (4): 704-708


    Many neural circuits process information in multiple distinct modes. For example, the hippocampus is involved in memory encoding, retrieval, and consolidation processes. These different mnemonic computations require processing of differing balances of current sensory input and previously stored associations. Here we explore patterns of activity in hippocampal output area CA1 associated with different information processing states. We discuss the evidence linking these patterns to specific inputs to CA1 and describe behavioral factors that are related to the balance of synaptic drive. We suggest that understanding the factors that influence information flow in the hippocampal circuit could provide important new insights into how neural circuits are reconfigured on the fly to perform different functions at different times.

    View details for DOI 10.1016/j.conb.2012.03.007

    View details for Web of Science ID 000309331200019

    View details for PubMedID 22480878

  • Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval NATURE NEUROSCIENCE Carr, M. F., Jadhav, S. P., Frank, L. M. 2011; 14 (2): 147-153


    The hippocampus is required for the encoding, consolidation and retrieval of event memories. Although the neural mechanisms that underlie these processes are only partially understood, a series of recent papers point to awake memory replay as a potential contributor to both consolidation and retrieval. Replay is the sequential reactivation of hippocampal place cells that represent previously experienced behavioral trajectories and occurs frequently in the awake state, particularly during periods of relative immobility. Awake replay may reflect trajectories through either the current environment or previously visited environments that are spatially remote. The repetition of learned sequences on a compressed time scale is well suited to promote memory consolidation in distributed circuits beyond the hippocampus, suggesting that consolidation occurs in both the awake and sleeping animal. Moreover, sensory information can influence the content of awake replay, suggesting a role for awake replay in memory retrieval.

    View details for DOI 10.1038/nn.2732

    View details for Web of Science ID 000286595400010

    View details for PubMedID 21270783

  • Experience-Dependent Development of Coordinated Hippocampal Spatial Activity Representing the Similarity of Related Locations JOURNAL OF NEUROSCIENCE Singer, A. C., Karlsson, M. P., Nathe, A. R., Carr, M. F., Frank, L. M. 2010; 30 (35): 11586-11604


    To learn we must identify and remember experiences uniquely but also generalize across experiences to extract common features. Hippocampal place cells can show similar firing patterns across locations, but the functional significance of this repetitive activity and the role of experience and learning in generating it are not understood. We therefore examined rat hippocampal place cell activity in the context of spatial tasks with multiple similar spatial trajectories. We found that, in environments with repeating elements, about half of the recorded place cells showed path-equivalent firing, where individual neurons are active in multiple similar locations. In contrast, place cells from animals performing a similar task in an environment with fewer similar elements were less likely to fire in a path-equivalent manner. Moreover, in the environment with multiple repeating elements, path equivalence developed with experience in the task, and increased path equivalence was associated with increased moment-by-moment correlations between pairs of path-equivalent neurons. As a result, correlated firing among path-equivalent neurons increased with experience. These findings suggest that coordinated hippocampal ensembles can encode generalizations across locations. Thus, path-equivalent ensembles are well suited to encode similarities among repeating elements, providing a framework for associating specific behaviors with multiple locations, while neurons without this repetitive structure maintain a distinct population code.

    View details for DOI 10.1523/JNEUROSCI.0926-10.2010

    View details for Web of Science ID 000281607300006

    View details for PubMedID 20810880