A functional interplay of bottom‐up and top‐down processing allows an individual to appropriately respond to the dynamic environment around them. These processing modalities can be represented as attractor states using a dynamical systems model of the brain. The transition probability to move from one attractor state to another is dependent on the stability, depth, neuromodulatory tone, and tonic changes in plasticity. However, how does the relationship between these states change in disease states, such as anxiety or depression? We describe bottom‐up and top‐down processing from Marr's computational‐algorithmic‐implementation perspective to understand depressive and anxious disease states. We illustrate examples of bottom‐up processing as basolateral amygdala signaling and projections and top‐down processing as medial prefrontal cortex internal signaling and projections. Understanding these internal processing dynamics can help us better model the multifaceted elements of anxiety and depression.

Affiliative social connections facilitate well-being and survival in numerous species. Engaging in social interactions requires positive and negative motivational drive, elicited through coordinated activity across neural circuits. However, the identity, interconnectivity, and functional encoding of social information within these circuits remains poorly understood. Here, we focused on downstream projections of dorsal raphe nucleus (DRN) dopamine neurons (DRNDAT), which we previously implicated in ‘negative drive’-induced social motivation. We show that three prominent DRNDAT projections – to the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), and posterior basolateral amygdala (BLP) – play separable roles in behavior, despite substantial collateralization. Photoactivation of the DRNDAT-CeA projection promoted social behavior and photoactivation of the DRNDAT-BNST projection promoted exploratory behavior, while the DRNDAT-BLP projection supported place avoidance, suggesting a negative affective state. Downstream regions showed diverse, region-specific, receptor expression, poising DRNDAT neurons to act through dopamine, neuropeptide, and glutamate transmission. Furthermore, we show ex vivo that the effect of DRNDAT photostimulation on downstream neuron excitability was predicted by baseline cell properties, suggesting cell-type-specific modulation. Collectively, these data indicate that DRNDAT neurons may bias behavior via precise modulation of cellular activity in broadly-distributed target structures.

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