Relay of affective stimuli from amygdala to thalamus parallels sensory pathways

The amygdala, the emotional sensor of the brain, is strongly connected with the posterior orbitofrontal cortex (pOFC), forming a pathway activated by reward learning. In addition, the amygdala innervates neurons in the mediodorsal thalamic nucleus (MD) that project to pOFC, forming a second, indirect route for the amygdala to inuence the pOFC sector of the prefrontal cortex. The indirect pathway that connects the amygdala and pOFC through the thalamus may be similar to sensory pathways connecting peripheral receptors with sensory cortices through sensory relay thalamic nuclei. The indirect pathway is morphologically distinct from the direct pathway; amygdalar pathway terminals in MD are larger than those in the pOFC, and likely derive from separate neuronal populations in the amygdala (Timbie and Barbas, Society for Neuroscience, 2013; J Neurosci, 2015). The synaptic interactions and potential specializations of amygdalar terminals in MD have not yet been described in comparison to other thalamic afferents. We addressed this issue by labeling amygdalar axons in MD in rhesus monkeys and compared them with retinal axons terminating in the lateral geniculate nucleus (LGN). We studied axon terminations in MD and LGN using serial section electron microscopy and analyzed pre- and post-synaptic elements by morphology. All amygdalar terminals in MD and retinal ganglion terminals in LGN contained multiple mitochondria, and were classed as round, large (RL) boutons. Amygdalar and retinal RL boutons contained excitatory type vesicles and formed several asymmetric (excitatory) synapses with dendrites of thalamocortical relay neurons and dendrites of inhibitory interneurons. In a significant proportion of these multi-synaptic arrangements, the inhibitory dendrites contained vesicles and formed symmetric synapses with the dendrite of the thalamocortical neuron. These novel findings reveal that amygdalar terminals in MD form synaptic triads, reminiscent of those found in sensory thalamic relay nuclei, like LGN. Our findings suggest that amygdalar inputs to MD can drive signals to cortex, ensuring efficient transmission of salient emotional information, akin to sensory thalamic relays.Published versio