Circuitry of emotion: integration in orbitofrontal cortex
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The amygdala and orbitofrontal cortex are critical sites for processing emotional content. The amygdala sends dense pathways preferentially to the posterior orbitofrontal cortex (pOFC) and to the magnocellular part of the mediodorsal thalamic nucleus (MDmc), which is itself robustly connected with pOFC. This tri-partite circuit is thought to be activated when associating stimuli with emotional value, and is necessary to flexibly adapt behavior to changing circumstances, but its features and synaptic interactions are unknown. Labeling of pathways with distinct neural tracers in rhesus monkeys revealed that amygdalar terminals in pOFC were denser and larger compared to those in other prefrontal cortices. Further, amygdalar terminals in pOFC were even larger than thalamocortical terminals, which are considered highly efficient drivers of cortical neurons. In comparison with thalamocortical pathways, amygdalar terminals innervated more excitatory neurons and were more frequently multisynaptic. These features suggest that the amygdala sends a highly efficient excitatory pathway to pOFC. Among a small proportion of innervated inhibitory neurons, the pathway from the amygdala to pOFC preferentially targeted the neurochemical classes of calbindin and calretinin inhibitory neurons in the upper layers, which are functionally suited to suppress distracting stimuli and enhance relevant signals. Further, the amygdalar pathway to MDmc targeted thalamocortical relay neurons, including those that project to pOFC, providing a second route for amygdalar signals to reach cortex. Neurochemical and morphological differences among terminals suggest that the direct pathway from the amygdala to pOFC and the indirect route through MDmc arise from separate neuronal populations in the amygdala. In MDmc, axon terminals from the amygdala formed synaptic triads, a thalamic specialization connecting excitatory projection neurons and local inhibitory neurons. This synaptic specialization is akin to what is found in sensory thalamic nuclei connecting peripheral sensory afferents with cortex. By analogy, the amygdala may act as a sensor of affective value, relaying signals about internal states to cortex through MDmc. The synaptic specializations shown here in the circuit that tightly interlinks the amygdala, MDmc, and pOFC shed light on the functional circuitry for emotional behavior and its disruption in psychiatric disorders such as phobias and obsessive compulsive disorder.