Biology subjects

Tien, N.-W.

Publications and source records attributed to Tien, N.-W..

5 recordsLinked to original sources

bioRxiv2025

Activation of the medial entorhinal cortex drives memory-guided navigation behavior

The cognitive map in the medial entorhinal cortex (MEC) is essential for spatial memory and exhibits experience-dependent changes. Yet, it remains unclear whether MEC activation is sufficient to bias the network toward memory-guided navigation, precluding a causal link between the MEC and spatial memory. To address this gap, we examined and optogenetically manipulated MEC activity as mice navigated a virtual track for a water reward based on memory. During learning, spatial activity in the pre-reward region showed the highest consistency along the track and closely paralleled improvements in reward-predictive behaviors. This elevated pre-reward consistency was widespread across MEC neurons, rather than confined to a particular cell type, indicating a network-level representation supporting reward prediction. Strikingly, optogenetic activation of MEC at non-reward locations biased reward-predictive behaviors toward stimulation sites, but only when stimulation patterns were spatially consistent. Consistent stimulation also induced anticipatory reward-seeking before stimulation onset and this behavior gradually developed with repeated stimulation, reflecting memory formation for stimulation locations. Moreover, in animals that failed to learn the track well, consistent pre-reward activation, alone or combined with landmark activation, significantly enhanced their reward prediction. Thus, spatially consistent MEC activation underlies memory-guided reward prediction, supporting a causal role for the MEC in spatial memory.

neuroscience↗

bioRxiv2025

Slow synaptic plasticity from the hippocampus underlies gradual mapping and fragmentation of novel spaces by grid cells

Animals construct internal "cognitive maps" of the world during navigation in spatial and non-spatial domains, with grid cells in the medial entorhinal cortex (MEC) playing a key role. This requires associating internal position estimates with external cues to reduce spatial uncertainty over time. However, how grid cell representations evolve in novel spaces to support map formation is unclear. To address this question, we longitudinally imaged calcium dynamics of grid cells over 10 days as mice learn operant tasks in novel virtual linear tracks. We observe that spatial tuning of grid cells is present immediately in novel tracks but evolves as a significant fraction of spatial fields shift backward on a run-by-run basis, within and across days. Backward shifts are more prevalent and persistent in successful learners. The fields gradually stabilize across days, anchored by landmarks, suggesting slow plasticity. The backward shifts partially reset daily, reflecting a slower consolidation timescale. While individual fields of a cell shift differentially, co-active fields of co-modular grid cells shift together, indicating their coupled dynamics on the same two-dimensional torus. Spatial learning leads to systematic changes and stabilization of their population phase trajectory, including lateral shift, rotation, and phase resets at landmarks, forming a landmark-fragmented representation for the environment. Next, we build an entorhinal-hippocampal model that provides a mechanistic explanation of the diverse phenomena - grid field shifts, increasing fidelity, and fragmentation of the spatial map - and predicts slow Hebbian plasticity in the hippocampus-to-entorhinal pathway. Supporting this, electrophysiology demonstrates that learning-performance-correlated weakening of local inhibition facilitates potentiation of indirect hippocampal inputs to superficial MEC. Together, our study provides multifaceted evidence of slow hippocampus-to-MEC plasticity, elucidating the formation of stable and fragmented cognitive maps that combine internal and cue-driven positional estimates in rich environments during learning. This mechanism may extend to broader memory processes involving this circuit.

neuroscience↗

bioRxiv2023

A consistent map in the medial entorhinal cortex supports spatial memory

The medial entorhinal cortex (MEC) is hypothesized to function as a cognitive map for memory-guided navigation. How this map develops during learning and influences memory remains unclear. By imaging MEC calcium dynamics while mice successfully learned a novel virtual environment over ten days, we discovered that the dynamics gradually became more spatially consistent and then stabilized. Additionally, grid cells in the MEC not only exhibited improved spatial tuning consistency, but also maintained stable phase relationships, suggesting a network mechanism involving synaptic plasticity and rigid recurrent connectivity to shape grid cell activity during learning. Increased c-Fos expression in the MEC in novel environments further supports the induction of synaptic plasticity. Unsuccessful learning lacked these activity features, indicating that a consistent map is specific for effective spatial memory. Finally, optogenetically disrupting spatial consistency of the map impaired memory-guided navigation in a well-learned environment. Thus, we demonstrate that the establishment of a spatially consistent MEC map across learning both correlates with, and is necessary for, successful spatial memory.

neuroscience↗

bioRxiv2023

Brain-wide neural activity underlying memory-guided movement

Behavior requires neural activity across the brain, but most experiments probe neurons in a single area at a time. Here we used multiple Neuropixels probes to record neural activity simultaneously in brain-wide circuits, in mice performing a memory-guided directional licking task. We targeted brain areas that form multi-regional loops with anterior lateral motor cortex (ALM), a key circuit node mediating the behavior. Neurons encoding sensory stimuli, choice, and actions were distributed across the brain. However, in addition to ALM, coding of choice was concentrated in subcortical areas receiving input from ALM, in an ALM-dependent manner. Choice signals were first detected in ALM and the midbrain, followed by the thalamus, and other brain areas. At the time of movement initiation, choice-selective activity collapsed across the brain, followed by new activity patterns driving specific actions. Our experiments provide the foundation for neural circuit models of decision-making and movement initiation.

neuroscience↗

bioRxiv2021

Layer-specific developmentally precise axon targeting of transient suppressed-by-contrast retinal ganglion cells (tSbC RGCs)

The mouse retina encodes diverse visual features in the spike trains of more than 40 retinal ganglion cell (RGC) types. Each RGC type innervates a specific subset of the more than 50 retinorecipient brain areas. Our catalog of RGC types and feature representations is nearing completion. Yet, we know little about where specific RGC types send their information. Furthermore, the developmental strategies by which RGC axons choose their targets and pattern their terminal arbors remain obscure. Here we identify a genetic intersection (Cck-Cre and Brn3cCKOAP) that selectively labels transient Suppressed-by-Contrast (tSbC) RGCs, a member of an evolutionarily conserved functionally mysterious RGC subclass. We find that tSbC RGCs selectively innervate the dorsolateral and ventrolateral geniculate nuclei of the thalamus (dLGN and vLGN), the superior colliculus (SC), and the nucleus of the optic tract (NOT). They binocularly innervate dLGN and vLGN but project only contralaterally to SC and NOT. In each target, tSbC RGC axons occupy a specific sublayer, suggesting that they restrict their input to specific circuits. The tSbC RGC axons span the length of the optic tract by birth and remain poised there until they simultaneously innervate their four targets around postnatal day five. The tSbC RGC axons make no errors in choosing their targets and establish mature stratification patterns from the outset. This precision is maintained in the absence of Brn3c. Our results provide the first map of SbC inputs to the brain, revealing a narrow target set, unexpected laminar organization, target-specific binocularity, and developmental precision. Significance statementIn recent years, we have learned a lot about the visual features encoded by retinal ganglion cells (RGCs), the eyes output neurons. In contrast, we know little about where RGCs send their information and how RGC axons, which carry this information, target specific brain areas during development. Here, we develop an intersectional strategy to label a unique RGC type, the tSbC RGC, and map its projections. We find that tSbC RGC axons are highly selective. They innervate few retinal targets and restrict their arbors to specific sublayers within these targets. The selective tSbC RGC projection patterns develop synchronously and without trial and error, suggesting molecular determinism and coordination.

neuroscience↗