Target cell-type specificity of a cortico-amygdala long range synaptic connection

An important function of the brain is to analyze sensory information, and to modulate animal behaviour according to previous experience. During processes of emotional learning, sensory percepts with a reinforcing quality, also called unconditioned stimuli (US), influence the quality of innocuous sensory stimuli. A brain structure involved in the integration of innocuous and reinforcing sensory stimuli is the lateral amygdala (LA), an input station to further amygdalar circuits. Little is known about which upstream brain regions convey US-information to the LA; however, evidence indicates that the posterior insular cortex, which processes nociceptive somatosensory information, might be a candidate. The LA microcircuit is composed of principal neurons and inhibitory interneurons; the latter play a prominent role in the control of local activity and plasticity. To investigate how the posterior insular cortex might recruit LA neurons, we used optogenetically-assisted circuit mapping in combination with genetic identification of cell types with Cre-mouse lines. Specifically, a VGluT2-Cre mouse line, producing a marker for excitatory neurons, and VIP-Cre and SOM-Cre mice as markers for two classes of inhibitory interneurons, were used. We found that VGluT2-Cre+ neurons received strong excitatory and feedforward inhibitory inputs from the posterior insular cortex. The excitatory input was sufficient to induce action potential firing, hence engaging the local circuit. VIP-Cre+ interneurons were moderately excited by posterior insular cortex input, and received strong feedforward inhibition. Both VIP-Cre+ and SOM-Cre+ interneurons also received feedforward, polysynaptic excitation, likely the result of the activity of local principal neurons. Finally, SOM-Cre+ interneurons received moderate excitatory and feedforward inhibitory input from the posterior insular cortex, and their connectivity probability was high. This study supports the notion that the posterior insular cortex can convey US-information to the LA, with the potential to strongly activate LA principal neurons. However, it suggests that a disinhibition of LA principal neurons through VIP interneurons, which has been observed in previous studies, might be shaped by additional afferents, possibly including neuromodulatory inputs. Through systematic recordings of input connections to defined neuron types in the LA, this study provides an entry point to the understanding of the synaptic connectivity rules that govern the activation of amygdalar circuits by incoming long-range cortical inputs.