Cross-species comparisons of neuronal morphology can reveal evolutionary diversification of cortical organization, but they remain limited by scarce human reconstructions, uncertain regional correspondence and scale-dependent morphometrics. Here we introduce a region correspondence framework to compare single-neuron dendritic morphology between mouse and human cortex. Corresponding cortical regions were rigorously defined by integrating anatomical annotations, functional evidence and registration stability and then evaluated using cross-species transcriptomic cell composition profiles. We analyzed dendritic reconstructions of 2,363 human and 16,011 mouse neurons from frontal, parietal and temporal lobes, comparing size-normalized local morphometric features within matched regions. Human cortical neurons showed higher branching frequency and shorter branching intervals, indicating compact local dendritic architecture beyond proportional size enlargement. Local morphology also showed stronger lobe-level separability in humans, associated mainly with spatial dendritic organization, whereas mouse separability reflected branching topology. Additional molecular, physiological, metabolic and geometric analyses showed partial concordance with morphology-based lobe separability, supporting divergent organization of cortical dendrites across species.

People with narcolepsy have intrusive episodes of muscle weakness known as cataplexy, which are usually triggered by strong, positive emotions. As cataplexy occurs almost exclusively during social interactions, we examined whether it is promoted by the prosocial neuropeptide oxytocin. In a mouse model of narcolepsy, social reunification triggered cataplexy, and an oxytocin antagonist blocked socially induced cataplexy episodes. Oxytocin tone and the activity of oxytocin receptor-expressing neurons in the central amygdala both increased just before cataplexy triggered by social stimuli. Chemo- and optogenetic manipulations demonstrated that oxytocin-responsive neurons in the central amygdala drive cataplexy by inhibiting brainstem neurons that suppress muscle atonia. In addition, chocolate, a rewarding stimulus associated with strong, positive emotions, also engages this oxytocin-amygdala pathway and triggers cataplexy in narcoleptic mice. Together, these findings show that oxytocin acts through the amygdala to promote cataplexy triggered by social and other rewarding stimuli, offering new opportunities for treating cataplexy.

TDP-43 proteinopathy is a hallmark of neurodegenerative disorders such as amyotrophic lateral sclerosis and frontotemporal dementia where mislocalization of TDP-43 has been observed in neurons and glial cells. However, the role of TDP-43 in microglia and the consequences of its loss of function remain unexplored. Combining magnetic resonance imaging, and confocal, and electron microscopy, we uncovered structural changes and myelin abnormalities in the early postnatal brain of mice lacking microglial TDP-43. Spatial transcriptomics further revealed an enriched interferon-responsive signature associated with oligodendrocyte dysfunction. Early depletion of microglial TDP-43 led to motor deficits in adult mice. Mechanistically, knocking out TDP-43 impaired microglial ability to engulf and degrade myelin. It also led to cryptic exon inclusion in the Tyrobp mRNA, resulting in truncated DAP12 protein, thus causing defective TREM2 signaling. Our findings reveal a role for TDP-43 in regulating the TREM2-DAP12 axis in mice, highlighting a previously unrecognized mechanism through which TDP-43 controls microglial function.

Neural activity fluctuates over a wide range of timescales within and across brain areas. Experimental observations suggest that diverse neural timescales reflect information in dynamic environments. However, the definitions and measurements of timescales derived from brain recordings vary across the literature. Moreover, these observations do not specify the mechanisms that underlie variations in timescales or whether specific timescales are necessary for neural computation and brain function. Here we synthesize three directions in which computational approaches can distill the broad set of empirical observations into quantitative and testable theories. We review (1) how different data analysis methods quantify timescales across distinct behavioral states and recording modalities; (2) how biophysical models provide mechanistic explanations for the emergence of diverse timescales; and (3) how task-performing networks and machine learning models uncover the functional relevance of neural timescales. This integrative computational perspective complements experimental investigations, providing a holistic view of how neural timescales reflect the relationships among brain structure, dynamics and behavior.

Successful spatial navigation requires rapid evaluation of potential future trajectories. Hippocampal 'theta sweeps', the sequential activation of place cells within individual theta cycles, exhibit predictive dynamics within the ideal timeframe for this role. However, whether these sequences reflect movement-related variables, perceptual targets or more cognitive goal-directed planning remains unresolved. Using data from the 'Honeycomb' maze, which dissociates head, movement and goal directions, we found that theta sweeps form vectors toward remembered goal locations independent of the rat's movement or heading directions. Stronger goal modulation preceded correct navigational choices, establishing the relevance of theta sweeps for spatial planning. A hierarchical continuous attractor network with goal-oriented directional inputs reproduced these findings and made several nontrivial predictions, which we confirmed empirically. Sequential activity during immobility-related sharp-wave ripples was also goal directed and, therefore, more aligned with theta sweeps than with previously experienced trajectories. Our findings identify hippocampal theta sweeps as neural substrates for online goal-directed planning.

During navigation, animals continuously sample their environment and plan routes to distant goals. Flexible navigation requires neural dynamics capable of rapidly deploying task-relevant information to direct behavior toward goals. Hippocampal spiking sequences within theta cycles, which sweep along spatial trajectories ahead of the animal, serve as a potential candidate. Previous research identified experience-independent, left-right-alternating theta sweeps as a mechanism for local spatial sampling. However, it remains unclear whether theta sweeps also facilitate trajectory evaluation toward distant, remembered goals. In rats performing goal-directed navigation in an open arena, we identified a distinct form of learning-dependent theta sequences that predicted upcoming goal-directed trajectories. These sequences coordinated with prefrontal cortical activity and were preferentially replayed during sharp-wave ripples. We described a circuit mechanism whereby egocentric goal-direction signals, combined with reduced feedback inhibition, generated goal-directed theta sweeps. Experience-dependent and goal-dependent theta sweeps thus provide a flexible mechanism for goal-directed navigation in open environments.