Distinct subnetworks of the mouse anterior thalamic nuclei

Despite significant advancements in identifying cell types in the mouse cerebral cortex, the classification of neuron types in the mouse thalamus remains largely incomplete. Specifically, the anterior thalamic nuclei (ATN), an integral component of the Papez circuit, encompass the anterodorsal (AD), anteroventral (AV), and anteromedial (AM) thalamic nuclei. Structurally, the ATN serve as a hub to facilitate communication among the neocortex, hippocampus, amygdala, and hypothalamus. Functionally, they play pivotal roles in regulating learning, memory, spatial navigation, and goal-directed behaviors. Thus, the ATN provide a promising avenue to investigate the relationship between structural and functional complexity with neuron type diversity. Our comprehensive and systematically collected macroscale pathway tracing data revealed several connectionally unique cell populations within the AM, AV, and AD that suggest several disparate parallel subnetworks run through each nucleus. Further, we applied genetic sparse labeling, brain clearing, 3D microscopic imaging, and computational informatics to catalog neuron types across the ATN, ascertained their brain-wide connectivity profile at the single neuron and synaptic resolutions, and characterized their morphological features. This study provides insights into how the prefrontal cortex, hippocampus, and amygdala interact through neuron type-specific ATN subnetworks to coordinate and synchronize both cognitive and emotional aspects of goal-directed behavior, resolving longstanding controversies surrounding the validity of the Papez circuit and its structural and functional roles.