@article {70215, title = {Signatures of remote planning in hippocampal replay}, journal = {bioRxiv}, year = {2025}, month = {2025 Dec 04}, abstract = {

During brief, intermittent {\textquotedblleft}replay{\textquotedblright} events, hippocampal activity can express navigational trajectories disconnected from both when and where they originally occurred. While replay biased toward immediate future goals has been observed, there is no evidence yet linking replay to planning beyond the next action. Here, we designed a sequential spatial working memory task which required rats to utilize information across multiple temporally separated actions. Remote replay events matched the animal{\textquoteright}s future navigational choices made after completing an intervening subtask. Critically, this occurred only when the replayed information was useful for reducing memory load, consistent with it being an active process. Our findings suggest these remote replay events are a neural correlate of episodic forethought, allowing animals to use memories to plan beyond their immediate surroundings.

}, doi = {10.64898/2025.12.02.691753}, url = {https://www.biorxiv.org/content/early/2025/12/04/2025.12.02.691753}, author = {Lustig, Brian and Wang, Yingxue and Romani, Sandro and Pastalkova, Eva and Lee, Albert K.} } @article {70220, title = {Time or distance encoding by hippocampal neurons via heterogeneous ramping rates.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Dec 17}, pages = {11083}, abstract = {

To navigate their environments effectively, animals frequently track time elapsed or distance traveled while seeking food and avoiding threats. The hippocampus is implicated in this process, but the neural mechanisms remain unclear. Using virtual reality tasks that require mice to integrate time or distance to collect a reward, we identified two previously unknown functional subpopulations of CA1 pyramidal neurons. Both subpopulations encode time or distance via distinct ramping dynamics. The first subpopulation exhibits a rapid, synchronous rise in activity upon movement-initiated integration. Subsequently, individual neurons ramp down at heterogeneous rates, creating progressively diverging firing rates that encode elapsed time or distance. Closed-loop optogenetic inactivation of somatostatin-positive (SST) interneurons counterintuitively reduced the ramping activity, leading mice to prematurely attempt reward collection, suggesting impaired time/distance estimation. Conversely, the second CA1 subpopulation shows opposite dynamics - an initial rapid suppression followed by a gradual ramp-up. Inactivating parvalbumin-positive (PV) interneurons diminished this initial suppression, resulting in transient attempts to collect reward near integration onset. These findings reveal parallel hippocampal circuits that initiate and maintain time or distance encoding, controlled by PV and SST interneurons, respectively, and provide insights into the neural computations supporting goal-directed navigation.

}, keywords = {Action Potentials, Animals, CA1 Region, Hippocampal, Hippocampus, Interneurons, Male, Mice, Mice, Inbred C57BL, Neurons, Optogenetics, Parvalbumins, Pyramidal Cells, Reward, Somatostatin, Virtual Reality}, issn = {2041-1723}, doi = {10.1038/s41467-025-67038-3}, url = {https://doi.org/10.1038/s41467-025-67038-3}, author = {Heldman, Raphael and Pang, Dongyan and Zhao, Xiaoliang and Mensh, Brett and Wang, Yingxue} } @article {65617, title = {Membrane potential dynamics underlying context-dependent sensory responses in the hippocampus.}, journal = {Nature Neuroscience}, volume = {23}, year = {2020}, month = {2020 Jul 1}, pages = {881-91}, abstract = {

As animals navigate, they must identify features within context. In the mammalian brain, the hippocampus has the ability to separately encode different environmental contexts, even when they share some prominent features. To do so, neurons respond to sensory features in a context-dependent manner; however, it is not known how this encoding emerges. To examine this, we performed electrical recordings in the hippocampus as mice navigated in two distinct virtual environments. In CA1, both synaptic input to single neurons and population activity strongly tracked visual cues in one environment, whereas responses were almost completely absent when the same cue was presented in a second environment. A very similar, highly context-dependent pattern of cue-driven spiking was also observed in CA3. These results indicate that CA1 inherits a complex spatial code from upstream regions, including CA3, that have already computed a context-dependent representation of environmental features.

}, issn = {1546-1726}, doi = {10.1038/s41593-020-0646-2}, author = {Zhao, Xinyu and Wang, Yingxue and Spruston, Nelson and Magee, Jeffrey C} } @article {46924, title = {Oscillatory patterns in hippocampus under light and deep isoflurane anesthesia closely mirror prominent brain states in awake animals.}, journal = {Hippocampus}, volume = {26}, year = {2015}, month = {2015 Jul 18}, pages = {102-9}, abstract = {

The hippocampus exhibits a variety of distinct states of activity under different conditions. For instance the rhythmic patterns of activity orchestrated by the theta oscillation during running and REM sleep are markedly different from the large irregular activity (LIA) observed during awake resting and slow wave sleep. We found that under different levels of isoflurane anesthesia activity in the hippocampus of rats displays two distinct states which have several qualities that mirror the theta and LIA states. These data provide further evidence that the two states are intrinsic modes of the hippocampus; while also characterizing a preparation that could be useful for studying the natural activity states in hippocampus. This article is protected by copyright. All rights reserved.

}, issn = {1098-1063}, doi = {10.1002/hipo.22494}, author = {Lustig, Brian and Wang, Yingxue and Pastalkova, Eva} } @article {45792, title = {Theta sequences are essential for internally generated hippocampal firing fields.}, journal = {Nature Neuroscience}, volume = {18}, year = {2015}, month = {2015 Feb}, pages = {282-8}, abstract = {

Sensory cue inputs and memory-related internal brain activities govern the firing of hippocampal neurons, but which specific firing patterns are induced by either of the two processes remains unclear. We found that sensory cues guided the firing of neurons in rats on a timescale of seconds and supported the formation of spatial firing fields. Independently of the sensory inputs, the memory-related network activity coordinated the firing of neurons not only on a second-long timescale, but also on a millisecond-long timescale, and was dependent on medial septum inputs. We propose a network mechanism that might coordinate this internally generated firing. Overall, we suggest that two independent mechanisms support the formation of spatial firing fields in hippocampus, but only the internally organized system supports short-timescale sequential firing and episodic memory.

}, issn = {1546-1726}, doi = {10.1038/nn.3904}, author = {Wang, Yingxue and Romani, Sandro and Lustig, Brian and Leonardo, Anthony and Pastalkova, Eva} }