The striatal direct and indirect pathways constitute the core for basal ganglia function in action control. Although both striatal D1- and D2-spiny projection neurons (SPNs) receive excitatory inputs from the cerebral cortex, whether or not they share inputs from the same cortical neurons, and how pathway-specific corticostriatal projections control behavior remain largely unknown. Here using a G-deleted rabies system in mice, we found that more than two-thirds of excitatory inputs to D2-SPNs also target D1-SPNs, while only one-third do so vice versa. Optogenetic stimulation of striatal D1- vs. D2-SPN-projecting cortical neurons differently regulate locomotion, reinforcement learning, and sequence behavior, implying the functional dichotomy of pathway-specific corticostriatal subcircuits. These results reveal the partially segregated yet asymmetrically overlapping cortical projections on striatal D1- vs. D2-SPNs, and that the pathway-specific corticostriatal subcircuits distinctly control behavior. It has important implications in a wide range of neurological and psychiatric diseases affecting cortico-basal ganglia circuitry.

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.

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.

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.

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

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

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.

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.

The striatal direct and indirect pathways constitute the core for basal ganglia function in action control. Although both striatal D1- and D2-spiny projection neurons (SPNs) receive excitatory inputs from the cerebral cortex, whether or not they share inputs from the same cortical neurons, and how pathway-specific corticostriatal projections control behavior remain largely unknown. Here using a G-deleted rabies system in mice, we found that more than two-thirds of excitatory inputs to D2-SPNs also target D1-SPNs, while only one-third do so vice versa. Optogenetic stimulation of striatal D1- vs. D2-SPN-projecting cortical neurons differently regulate locomotion, reinforcement learning, and sequence behavior, implying the functional dichotomy of pathway-specific corticostriatal subcircuits. These results reveal the partially segregated yet asymmetrically overlapping cortical projections on striatal D1- vs. D2-SPNs, and that the pathway-specific corticostriatal subcircuits distinctly control behavior. It has important implications in a wide range of neurological and psychiatric diseases affecting cortico-basal ganglia circuitry.