Abstract
Affective responses depend on assigning value to environmental predictors of threat or reward. Neuroanatomically, this affective value is encoded at both cortical and subcortical levels. However, the purpose of this distributed representation across functional hierarchies remains unclear. Using fMRI in mice, we mapped a discrete cortico-limbic loop between insular cortex (IC), central amygdala (CE), and nucleus basalis of Meynert (NBM), which decomposes the affective value of a conditioned stimulus (CS) into its salience and valence components. In IC, learning integrated unconditioned stimulus (US)-evoked bodily states into CS valence. In turn, CS salience in the CE recruited these CS representations bottom-up via the cholinergic NBM. This way, the CE incorporated interoceptive feedback from IC to improve discrimination of CS valence. Consequently, opto-/chemogenetic uncoupling of hierarchical information flow disrupted affective learning and conditioned responding. Dysfunctional interactions in the IC↔CE/NBM network may underlie intolerance to uncertainty, observed in autism and related psychiatric conditions.
Highlights
Brains learn about environmental predictors to adapt future behavioral choices (LeDoux, 2000)
We found that M1R antagonism abolished conditioned stimulus (CS)-induced spike-field coherence (SFC), indicating that cholinergic signaling via M1R mediates cortical gain control in the insular cortex (IC) (Figure 4E)
Our study successfully integrated brain wide network analysis from high field small animal functional MRI (fMRI) with circuit physiology, and thereby mapped the IC$central amygdala (CE)/nucleus basalis of Meynert (NBM) network as a distinct functional unit. This approach uncovered a basic functional motif that encodes complementary CS features at different hierarchies and stages of Pavlovian learning
Summary
Brains learn about environmental predictors to adapt future behavioral choices (LeDoux, 2000). The interoceptive insular cortex (IC) plays a fundamental role in sensing these stimuli (Avery et al, 2017; Craig, 2002; Critchley et al, 2004; Livneh et al, 2020; Segerdahl et al, 2015) In this regard, limbic cortices, in particular the IC, are at the apex of sensory integration and represent interoceptive models and associated states in their most abstracted form (Chanes and Barrett, 2016; Pezzulo et al, 2018). Therein, hierarchical interaction between IC and CE assembles interoceptive CS value from salience and valence dimensions, which is internally gated by the NBM. Such emergent functions are difficult to study in isolated cortical and subcortical network elements, so they remain largely uncharted. We here mapped the network-wide organization of CS and US features in IC$CE/NBM circuitry and explored the hierarchical information flow underlying affective associations
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