Publications by authors named "Sheng-Jia Zhang"

Head-direction (HD) cells are a fundamental component in the hippocampal-entorhinal circuit for spatial navigation and help maintain an internal sense of direction to anchor the orientation in space. A classical HD cell robustly increases its firing rate when the head is oriented toward a specific direction, with each cell tuned to only one direction. Although unidirectional HD cells are reported broadly across multiple brain regions, computation modelling has predicted the existence of multiple equilibrium states of HD network, which has yet to be proven.

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The medial prefrontal cortex (mPFC) is a key brain structure for higher cognitive functions such as decision-making and goal-directed behavior, many of which require awareness of spatial variables including one's current position within the surrounding environment. Although previous studies have reported spatially tuned activities in mPFC during memory-related trajectory, the spatial tuning of mPFC network during freely foraging behavior remains elusive. Here, we reveal geometric border or border-proximal representations from the neural activity of mPFC ensembles during naturally exploring behavior, with both allocentric and egocentric boundary responses.

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Article Synopsis
  • Spatially modulated grid cells were identified in the rat's secondary visual cortex (V2) while the rats navigated, but their function and underlying processes are still unclear.
  • A biologically inspired neural network was trained for a 2D navigation task using multiple sensory inputs, revealing grid-like responses in both excitatory and inhibitory units.
  • The study also identified connections between grid patterns and their functionality in various tasks, suggesting V2 grid cells share computational mechanisms for both spatial navigation and visual recognition.
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  • * Recent research suggests that grid-like representations may play a crucial role in various perceptual and cognitive tasks, especially those related to movement and mental navigation.
  • * The authors encourage the use of computational modeling to explore grid cell theories and hope that their insights will foster new testable hypotheses in future experiments.
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  • Head direction (HD) cells are crucial for spatial navigation and are connected to spatial memory, acting as an internal compass in the brain.
  • The study highlights two types of HD cells in the somatosensory cortex: regular-spiking (RS) and fast-spiking (FS), with FS cells displaying sharper directionality and unique firing patterns.
  • The coexistence of FS and RS HD cells in different layers suggests a new way of spatial representation, challenging previous beliefs about the tuning of FS interneurons to sensory stimuli.
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  • Spatially selective firing of various cell types, including place and grid cells, is essential for spatial navigation within the hippocampal-entorhinal complex, but head direction cells are found throughout the brain with different representations.
  • Research indicates that sensory inputs, particularly from vision, influence spatial representation in this area, prompting an investigation into other senses like touch.
  • The study revealed similar spatially selective firing patterns in the somatosensory cortex of foraging rats, suggesting that this area of the brain also processes spatial information, which could have implications for rehabilitation through brain-machine interfaces.
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Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuromodulation approaches are, however, invasive since surgical implantation of an optical fiber or wire electrode is required. Here, we have invented a non-invasive magnetogenetics that combines the genetic targeting of a magnetoreceptor with remote magnetic stimulation.

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  • Spatial navigation relies on understanding the relationship between where we currently are and where we want to go, and hippocampal neurons seem to track both current position and future paths.
  • A new study identifies a neural circuit involving the medial prefrontal cortex and the nucleus reuniens of the thalamus that's vital for the hippocampus to represent routes through an environment in rats.
  • Disabling the nucleus reuniens significantly diminished the neurons' ability in the CA1 region of the hippocampus to reflect trajectory information, indicating that this thalamic area is crucial for communication in the brain's navigation networks.
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The mammalian space circuit is known to contain several functionally specialized cell types, such as place cells in the hippocampus and grid cells, head-direction cells and border cells in the medial entorhinal cortex (MEC). The interaction between the entorhinal and hippocampal spatial representations is poorly understood, however. We have developed an optogenetic strategy to identify functionally defined cell types in the MEC that project directly to the hippocampus.

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  • Principal cells in layer V of the medial entorhinal cortex (MEC) play a key role in the cortical-hippocampal network, receiving inputs from various cortical areas, especially the retrosplenial cortex (RSC).
  • The study found that RSC axons primarily create excitatory synapses on layer V pyramidal cells, with a majority forming asymmetrical synapses on dendritic spines.
  • Optogenetic experiments confirmed that RSC input induces excitatory postsynaptic potentials (EPSPs), showing its importance in connecting entorhinal, cortical, and hippocampal circuits.
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We used a combined optogenetic-electrophysiological strategy to determine the functional identity of entorhinal cells with output to the place-cell population in the hippocampus. Channelrhodopsin-2 (ChR2) was expressed selectively in the hippocampus-targeting subset of entorhinal projection neurons by infusing retrogradely transportable ChR2-coding recombinant adeno-associated virus in the hippocampus. Virally transduced ChR2-expressing cells were identified in medial entorhinal cortex as cells that fired at fixed minimal latencies in response to local flashes of light.

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  • Grid cells in the medial entorhinal cortex are critical for how mammals perceive space and their firing patterns are thought to arise from complex network dynamics.
  • Researchers recorded from over 600 neuron pairs in rat brain slices, focusing on stellate cells, which are key players in this network, and found that they are primarily interconnected through inhibitory interneurons.
  • The study also used a model to show that stable firing patterns of grid cells can emerge from a simple network primarily composed of inhibitory connections, indicating that this inhibitory circuitry is enough to produce grid-like firing in these cells.
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  • CREB is a key transcription factor in neurons, activated through phosphorylation at serine 133 by the CaMK IV signaling pathway, which is essential for neuroprotection and adaptive processes in the brain.
  • * Researchers used recombinant adeno-associated virus to increase wild type CREB levels, resulting in boosted neuroprotective activity, while overexpressing a mutant form (mCREB) caused increased cell death.
  • * The study concluded that normal levels of wild type CREB significantly influence hippocampal neuron survival by enhancing the expression of neuroprotective genes like bdnf and others within the Activity-regulated Inhibitor of Death (AID) gene family.
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  • * ATF3 acts as a transcriptional repressor that protects hippocampal neurons from apoptosis and damage caused by either excessive NMDA receptor activation or oxygen-glucose deprivation.
  • * Modulating ATF3's function can either protect neurons or induce death, highlighting the importance of understanding nuclear calcium signaling and gene regulation in preventing neuronal loss related to age and disease.
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Synaptic activity can boost neuroprotection through a mechanism that requires synapse-to-nucleus communication and calcium signals in the cell nucleus. Here we show that in hippocampal neurons nuclear calcium is one of the most potent signals in neuronal gene expression. The induction or repression of 185 neuronal activity-regulated genes is dependent upon nuclear calcium signaling.

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  • The study investigates the role of calcium/calmodulin-dependent protein kinase IV (CaMKIV) in the nucleus accumbens of mice, aiming to understand its influence on emotional responses and gene transcription regulated by CREB.
  • Researchers used a gene transfer technique to inhibit CaMKIV and performed various behavioral tests to assess the impact on anxiety and locomotion.
  • Results showed that while CaMKIV inhibition did not affect general motor activity or sensorimotor responses, it did increase anxiety-like behaviors in specific social interaction tests.
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  • NMDA receptors have dual roles in neurons: they can promote survival or lead to cell degeneration and loss, depending on their activation location.
  • Whole-genome expression profiling shows that they activate two distinct gene-expression programs that influence neuronal fates differently.
  • Synaptic NMDA receptors trigger protective gene expression, while extrasynaptic receptors activate genes that induce neuron death, highlighting the importance of calcium signaling in this process.
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