Marielena Sosa

All Publications

• The grid code for ordered experience. Nature reviews. Neuroscience Rueckemann, J. W., Sosa, M., Giocomo, L. M., Buffalo, E. A. 2021

  Abstract

  Entorhinal cortical grid cells fire in a periodic pattern that tiles space, which is suggestive of a spatial coordinate system. However, irregularities in the grid pattern as well as responses of grid cells in contexts other than spatial navigation have presented a challenge to existing models of entorhinal function. In this Perspective, we propose that hippocampal input provides a key informative drive to the grid network in both spatial and non-spatial circumstances, particularly around salient events. We build on previous models in which neural activity propagates through the entorhinal-hippocampal network in time. This temporal contiguity in network activity points to temporal order as a necessary characteristic of representations generated by the hippocampal formation. We advocate that interactions in the entorhinal-hippocampal loop build a topological representation that is rooted in the temporal order of experience. In this way, the structure of grid cell firing supports a learned topology rather than a rigid coordinate frame that is bound to measurements of the physical world.

  View details for DOI 10.1038/s41583-021-00499-9

  View details for PubMedID 34453151

• Navigating for reward. Nature reviews. Neuroscience Sosa, M., Giocomo, L. M. 2021

  Abstract

  An organism's survival can depend on its ability to recall and navigate to spatial locations associated with rewards, such as food or a home. Accumulating research has revealed that computations of reward and its prediction occur on multiple levels across a complex set of interacting brain regions, including those that support memory and navigation. However, how the brain coordinates the encoding, recall and use of reward information to guide navigation remains incompletely understood. In this Review, we propose that the brain's classical navigation centres - the hippocampus and the entorhinal cortex - are ideally suited to coordinate this larger network by representing both physical and mental space as a series of states. These states may be linked to reward via neuromodulatory inputs to the hippocampus-entorhinal cortex system. Hippocampal outputs can then broadcast sequences of states to the rest of the brain to store reward associations or to facilitate decision-making, potentially engaging additional value signals downstream. This proposal is supported by recent advances in both experimental and theoretical neuroscience. By discussing the neural systems traditionally tied to navigation and reward at their intersection, we aim to offer an integrated framework for understanding navigation to reward as a fundamental feature of many cognitive processes.

  View details for DOI 10.1038/s41583-021-00479-z

  View details for PubMedID 34230644

• Dorsal and Ventral Hippocampal Sharp-Wave Ripples Activate Distinct Nucleus Accumbens Networks. Neuron Sosa, M., Joo, H. R., Frank, L. M. 2020; 105 (4): 725-741.e8

  Abstract

  Memories of positive experiences link places, events, and reward outcomes. These memories recruit interactions between the hippocampus and nucleus accumbens (NAc). Both dorsal and ventral hippocampus (dH and vH) project to the NAc, but it remains unknown whether dH and vH act in concert or separately to engage NAc representations related to space and reward. We recorded simultaneously from the dH, vH, and NAc of rats during an appetitive spatial task and focused on hippocampal sharp-wave ripples (SWRs) to identify times of memory reactivation across brain regions. Here, we show that dH and vH awake SWRs occur asynchronously and activate distinct and opposing patterns of NAc spiking. Only NAc neurons activated during dH SWRs were tuned to task- and reward-related information. These temporally and anatomically separable hippocampal-NAc interactions point to distinct channels of mnemonic processing in the NAc, with the dH-NAc channel specialized for spatial task and reward information. VIDEO ABSTRACT.

  View details for DOI 10.1016/j.neuron.2019.11.022

  View details for PubMedID 31864947

  View details for PubMedCentralID PMC7035181

• Constant Sub-second Cycling between Representations of Possible Futures in the Hippocampus CELL Kay, K., Chung, J. E., Sosa, M., Schor, J. S., Karlsson, M. P., Larkin, M. C., Liu, D. F., Frank, L. M. 2020; 180 (3): 552-+

  Abstract

  Cognitive faculties such as imagination, planning, and decision-making entail the ability to represent hypothetical experience. Crucially, animal behavior in natural settings implies that the brain can represent hypothetical future experience not only quickly but also constantly over time, as external events continually unfold. To determine how this is possible, we recorded neural activity in the hippocampus of rats navigating a maze with multiple spatial paths. We found neural activity encoding two possible future scenarios (two upcoming maze paths) in constant alternation at 8 Hz: one scenario per ∼125-ms cycle. Further, we found that the underlying dynamics of cycling (both inter- and intra-cycle dynamics) generalized across qualitatively different representational correlates (location and direction). Notably, cycling occurred across moving behaviors, including during running. These findings identify a general dynamic process capable of quickly and continually representing hypothetical experience, including that of multiple possible futures.

  View details for DOI 10.1016/j.cell.2020.01.014

  View details for Web of Science ID 000512977500011

  View details for PubMedID 32004462

• Are We There Yet? Identification of Reward-Selective Cells in the Hippocampus. Neuron Sosa, M., Frank, L. M. 2018; 99 (1): 7-10

  Abstract

  Navigation to a previously visited reward site requires a reliable and accurate spatial memory. In this issue of Neuron, Gauthier and Tank (2018) use two-photon calcium imaging to uncover a discrete hippocampal subpopulation specialized for encoding reward location.

  View details for DOI 10.1016/j.neuron.2018.06.037

  View details for PubMedID 30001513

• Distinct hippocampal-cortical memory representations for experiences associated with movement versus immobility. eLife Yu, J. Y., Kay, K., Liu, D. F., Grossrubatscher, I., Loback, A., Sosa, M., Chung, J. E., Karlsson, M. P., Larkin, M. C., Frank, L. M. 2017; 6

  Abstract

  While ongoing experience proceeds continuously, memories of past experience are often recalled as episodes with defined beginnings and ends. The neural mechanisms that lead to the formation of discrete episodes from the stream of neural activity patterns representing ongoing experience are unknown. To investigate these mechanisms, we recorded neural activity in the rat hippocampus and prefrontal cortex, structures critical for memory processes. We show that during spatial navigation, hippocampal CA1 place cells maintain a continuous spatial representation across different states of motion (movement and immobility). In contrast, during sharp-wave ripples (SWRs), when representations of experience are transiently reactivated from memory, movement- and immobility-associated activity patterns are most often reactivated separately. Concurrently, distinct hippocampal reactivations of movement- or immobility-associated representations are accompanied by distinct modulation patterns in prefrontal cortex. These findings demonstrate a continuous representation of ongoing experience can be separated into independently reactivated memory representations.

  View details for DOI 10.7554/eLife.27621

  View details for PubMedID 28826483

  View details for PubMedCentralID PMC5576488

• A hippocampal network for spatial coding during immobility and sleep. Nature Kay, K., Sosa, M., Chung, J. E., Karlsson, M. P., Larkin, M. C., Frank, L. M. 2016; 531 (7593): 185-90

  Abstract

  How does an animal know where it is when it stops moving? Hippocampal place cells fire at discrete locations as subjects traverse space, thereby providing an explicit neural code for current location during locomotion. In contrast, during awake immobility, the hippocampus is thought to be dominated by neural firing representing past and possible future experience. The question of whether and how the hippocampus constructs a representation of current location in the absence of locomotion has been unresolved. Here we report that a distinct population of hippocampal neurons, located in the CA2 subregion, signals current location during immobility, and does so in association with a previously unidentified hippocampus-wide network pattern. In addition, signalling of location persists into brief periods of desynchronization prevalent in slow-wave sleep. The hippocampus thus generates a distinct representation of current location during immobility, pointing to mnemonic processing specific to experience occurring in the absence of locomotion.

  View details for DOI 10.1038/nature17144

  View details for PubMedID 26934224

  View details for PubMedCentralID PMC5037107

• Neural Activity Patterns Underlying Spatial Coding in the Hippocampus Behavioral Neuroscience of Learning and Memory Sosa, M., Gillespie, A. K., Frank, L. M. edited by Clark, R. E., Martin, S. J. Springer. 2016: 43–100