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Modulation of speed-dependent acetylcholine release in the hippocampus by spatial task engagement.

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Acetylcholine (ACh) plays important roles in memory encoding and attention in the hippocampus. However, changes in ACh signaling patterns during different neural and behavioral states remain poorly understood. Here, we used a genetically encoded ACh sensor and multi-plane, dual-color two-photon microscopy to establish the ACh signaling patterns in hippocampal CA1 of mice performing spatial behaviors. We observed spatially homogeneous signaling across volumes spanning hundreds of microns, which was positively correlated with locomotion speed. In novel environments, there was an increase in release persisting for dozens of laps while maintaining a positive speed correlation. When mice voluntarily disengaged, the magnitude of the speed-correlated release decreased, and this was accompanied by reduced place cell numbers and less precise place maps. Administration of scopolamine mimicked the effects of voluntary disengagement in terms of behavior and place cell metrics. These findings establish behaviorally correlated ACh signaling patterns in the hippocampus.

Unique Transcriptomic Cell Types of the Granular Retrosplenial Cortex are Preserved Across Mice and Rats Despite Dramatic Changes in Key Marker Genes.

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The granular retrosplenial cortex (RSG) supports memory, orientation, and fear processing. The mouse RSG contains several cell types that are remarkably distinct from those found in other cortical regions, including low rheobase neurons that dominate layer 2/3 (L2/3 LR) and similarly exclusive pyramidal cells in layer 5a (L5a RSG). While the functions of the RSG are extensively studied in both mice and rats, it remains unknown if the transcriptomically unique cell types of the mouse RSG are evolutionarily conserved in rats. Here, we show that mouse and rat RSG contain the same unique cell types, with L2/3 LR and L5a RSG cell types together representing more than 50% of all RSG neurons in each species. This preservation of cell types in male and female rats happens despite dramatic changes in key cell-type-specific marker genes, with the expression that selectively tags mouse L5a RSG neurons completely absent in rats. Important for Cre-driver line development, we identify alternative, cross-species genes that can be used to selectively target the cell types of the RSG in both mice and rats. Our results show that the unique cell types of the RSG are conserved across millions of years of evolution and emphasize stark species-specific differences in marker genes that need to be considered when making cell-type-specific knock-in lines across species. The retrosplenial cortex is important for memory, spatial orientation, fear processing, and imagining oneself in the future. Lesions to this brain region in humans lead to an inability to find one's way home. The mouse granular retrosplenial cortex (RSG) contains neuron types that are particularly distinct from those found in neighboring regions. Whether these distinct neurons are preserved across species remains unknown. Here, we show that all cell types of the mouse RSG are also found in rats, and the unique RSG cell types dominate the region in each species. These results suggest that the unique RSG neurons support evolutionarily important functions that facilitate the preservation of these neurons across millions of years of evolution.

Recurrent circuits encode de novo visual center-surround computations in the mouse superior colliculus.

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Models of visual salience detection rely on center-surround interactions, yet it remains unclear how these computations are distributed across retinal, cortical, and subcortical circuits due to their overlapping contributions. Here, we reveal a de novo collicular mechanism for surround suppression by combining patterned optogenetics with whole-cell recordings from individual neurons in the mouse superficial superior colliculus (SCs). Center zones were defined by monosynaptic input from channelrhodopsin-expressing retinal ganglion cells in collicular midbrain slices. Surround network optoactivation suppressed center responses compared to center-only input. This suppression is excitatory in origin, arising from the withdrawal of center excitation via surround-driven inhibition of local recurrent excitatory circuits, as demonstrated by cell-type-specific trans-synaptic tracing and computational modeling. These findings identify a local circuit mechanism for saliency computation in the SCs, independent of cortical input.
Latest Updated Curations

Navigation & Localization

 
 
Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.

Basal Ganglia Advances

 
 
Basal Ganglia Advances is a collection highlighting research on the structure, function, and disorders of the basal ganglia. It features studies spanning neuroscience, clinical insights, and computational models, serving as a hub for advances in movement, cognition, and behavior.

Progress in Voltage Imaging

 
 
Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.
Most Popular Recent Articles

A whole-brain male mouse atlas of long-range inputs to histaminergic neurons.

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The precise structural and functional characteristics of input circuits targeting histaminergic neurons remain poorly understood. Here, using a rabies virus retrograde tracing system combined with fluorescence micro-optical sectioning tomography, we construct a 3D monosynaptic long-range input atlas of male mouse histaminergic neurons. We identify that the hypothalamus, thalamus, pallidum, and hippocampus constitute major input sources, exhibiting diverse spatial distribution patterns and neuronal type ratios. Notably, a specific layer distribution pattern and co-projection structures of upstream cortical neurons are well reconstructed at single-cell resolution. As histaminergic system is classically involved in sleep-wake regulation, we demonstrate that the lateral septum (predominantly supplying inhibitory inputs) and the paraventricular nucleus of the thalamus (predominantly supplying excitatory inputs) establish monosynaptic connections, exhibiting distinct functional dynamics and regulatory roles in rapid-eye-movement sleep. Collectively, our study provides a precise long-range input map of mouse histaminergic neurons at mesoscopic scale, laying a solid foundation for future systematic study of histaminergic neural circuits.

Visual gamma stimulation induces 40 Hz neural oscillations in the human hippocampus and alters phase synchrony and lag.

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Nonpharmaceutical approaches based on gamma entrainment using sensory stimuli (GENUS) have shown promise in reducing Alzheimer's disease pathology in mouse models. While human studies remain limited, GENUS has been shown to alleviate aspects of neurodegeneration in patients with Alzheimer's disease. In this study, we analyze intracranial EEG data from 490 contacts across eleven patients with refractory epilepsy in response to three visual stimulation conditions. We find that 40 Hz visual stimulation successfully entrains neural activity beyond early visual areas, including the hippocampus and other cortical regions such as the temporal and frontal lobes. Additionally, we show that synchronization increases between the hippocampus and other cortical areas in response to the 40 Hz visual stimulation. Furthermore, combining stimulation with a simple visual oddball task alters the direction of information flow from frontal regions to the hippocampus and enhances both the strength and spatial extent of neural entrainment. These findings highlight the potential influence of cognitive engagement during sensory gamma stimulation and provide additional insights into the neurophysiological effects of 40 Hz visual stimulation.

Synchronous ensembles of hippocampal CA1 pyramidal neurons during novel exploration.

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Synchronous neuronal ensembles play a pivotal role in the consolidation of long-term memory in the hippocampus. However, their organization during the acquisition of spatial memory remains less clear. In this study, we used neuronal population voltage imaging to investigate the synchronization patterns of mice CA1 pyramidal neuronal ensembles during the exploration of a new environment, a critical phase for spatial memory acquisition. We found synchronous ensembles comprising approximately 40% of CA1 pyramidal neurons, firing simultaneously in brief windows (~25ms) during immobility and locomotion in novel exploration. Notably, these synchronous ensembles were not associated with contralateral ripple oscillations but were instead phase-locked to theta waves recorded in the contralateral CA1 region. Moreover, the subthreshold membrane potentials of neurons exhibited coherent intracellular theta oscillations with a depolarizing peak at the moment of synchrony. Among newly formed place cells, pairs with more robust synchronization during locomotion displayed more distinct place-specific activities. These findings underscore the role of synchronous ensembles in coordinating place cells of different place fields.
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