ABSTRACT
The cerebral cortex comprises diverse types of glutamatergic projection neurons (PNs) generated from radial glial progenitors (RGs) through either direct neurogenesis or indirect neurogenesis (iNG) via intermediate progenitors (IPs). A foundational concept in corticogenesis is the "inside-out" model whereby successive generations of PNs sequentially migrate to deep then progressively more superficial layers, but its biological significance remains unclear; and the role of iNG in this process is unknown. Using genetic strategies linking PN birth-dating to projection mapping in mice, we found that the laminar deployment of IP-derived PNs substantially deviate from an inside-out rule: PNs destined to non-consecutive layers are generated at the same time, and different PN types of the same layer are generated at non-contiguous times. The overarching scheme of iNG is the sequential specification and precise laminar deployment of projection-defined PN types, which may contribute to the orderly assembly of cortical output channels and processing streams. HIGHLIGHTS: - Each IP is fate-restricted to generate a pair of near-identical PNs - Corticogenesis involves the orderly generation of fate-restricted IP temporal cohorts - IP temporal cohorts sequentially as well as concurrently specify multiple PN types - The deployment of PN types to specific layers does not follow an inside-out order.
ABSTRACT
The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally opposing information and participates in establishing valence-specific behaviors remains unclear. Here, by targeting Fezf2-expressing neurons in the BLA, we identify and characterize two functionally distinct classes in behaving mice, the negative-valence neurons and positive-valence neurons, which innately represent aversive and rewarding stimuli, respectively, and through learning acquire predictive responses that are essential for punishment avoidance or reward seeking. Notably, these two classes of neurons receive inputs from separate sets of sensory and limbic areas, and convey punishment and reward information through projections to the nucleus accumbens and olfactory tubercle, respectively, to drive negative and positive reinforcement. Thus, valence-specific BLA neurons are wired with distinctive input-output structures, forming a circuit framework that supports the roles of the BLA in encoding, learning and executing valence-specific motivated behaviors.
