bioRxiv Subject Collection: Neuroscience's Journal
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Thursday, December 19th, 2024
| Time |
Event |
| 2:45a |
Comparative mapping of single-cell transcriptomic landscapes in neurodegenerative diseases
INTRODUCTION: Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), and Parkinson's disease (PD) represent a spectrum of neurodegenerative disorders (NDDs). Here, we performed the first direct comparison of their transcriptomic landscapes. METHODS: We profiled the whole transcriptomes of NDD cortical tissue by snRNA-seq. We used computational analyses to identify common and distinct differentially expressed genes (DEGs), biological pathways, vulnerable and disease-driver cell subtypes, and alteration in cell-to-cell interactions. RESULTS: The same vulnerable inhibitory neuron subtype was depleted in both AD and DLB. Potentially disease-driving neuronal cell subtypes were present in both PD and DLB. Cell-cell communication was predicted to be increased in AD but decreased in DLB and PD. DEGs were most commonly shared across NDDs within inhibitory neuron subtypes. Overall, we observed the greatest transcriptomic divergence between AD and PD, while DLB exhibited an intermediate transcriptomic signature. DISCUSSION: These results help explain the clinicopathological spectrum of this group of NDDs and provide unique insights into the shared and distinct molecular mechanisms underlying the pathogenesis of NDDs. | | 2:45a |
Mechanisms for plastic landmark anchoring in zebrafish compass neurons
Vision is a sensory modality particularly important for navigation, as it can inform animals of their current heading (i.e. visual landmarks) as well as its changes (i.e. optic flow). It has been shown that head direction (HD) neurons in various species incorporate the visual cues into their heading estimates. However, circuit mechanisms underlying this process remain still elusive in vertebrates. Here, we asked if and how the recently identified HD cells in the larval zebrafish - one of the smallest vertebrate models - incorporate visual information. By combining two-photon microscopy with a panoramic virtual reality setup, we demonstrate that the zebrafish HD cells can reliably track the orientation of multiple visual scenes, exploiting both landmark and optic flow cues. The mapping between landmark cues and the heading estimates is idiosyncratic across fish, and experience-dependent. Furthermore, we show that the landmark tracking requires the lateralized projection from the habenula to the interpeduncular nucleus (IPN), where the HD neuron processes innervate. The physiological and morphological parallels suggest that a Hebbian mechanism similar to the fly ring neuron is at work in the habenula axons. Overall, the observations that the hindbrain HD cells of the larval zebrafish lacking an elaborate visual telencephalon shed new light on the evolution of the navigation circuitry in vertebrates. |
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