Dual thalamic drive defines the intra-amygdala wiring complexity

The amygdala plays a key role in affective behaviors by integrating incoming signals and conveying them towards subcortical output regions. Current models suggest a serial information flow within the amygdala from the lateral and basolateral towards the central subnuclei driven by incoming thalamic and cortical excitation. However, due to the lack of universally accepted parcellation principles, the precise connectivity and thus, the signal propagation within the circuit remain debated. Using a molecular-based parcellation, our subnucleus-specific anatomical and electrophysiological mapping revealed a previously overlooked complexity in the intra-amygdala wiring pattern in mice. Specifically, the intra-amygdala signal transfer relies on separate lateral thalamus-driven routes via the lateral subnucleus mostly bypassing the anterior basolateral and centrolateral subnuclei. In contrast, the anterior basolateral nucleus, innervated by the dorsal midline thalamus, supplies mostly extra-, but not intra-amygdala routes. We also demonstrated that a similar dual thalamo-cortico-amygdala organization exists in the human brain. Collectively, our findings identified unconventional amygdala wiring principles challenging the traditional serial lateral-basolateral-central stream model which can redefine our understanding of behaviorally relevant intra-amygdala computations.