Lateral Amygdala to Auditory Cortex Projections Play a Key Role in Fear Conditioning and Exhibit Selective Synaptic Remodeling after Fear Learning


  A recent paper published in Nature Neuroscience uncovered a pathway from the lateral amygdala to the auditory cortexin mice, which plays a key role in auditory fear memory, and undergoes pathway-specific synaptic plasticity after fear conditioning. Dual-color in vivo two-photon imaging of pre- and postsynaptic structures showed that essentially all new synaptic contacts were made by adding new partners to existing synaptic elements, suggesting a rule for synapse formation in adult brain. This work was carried out by Dr. POO Muming ’s group at the Institute of Neuroscience, CAS.

  Classical fear conditioning is widely used for studying learning and memory. In auditory fear conditioning, mice learn to associate a sound with a foot-shock, and exhibit fear responses to the sound presentation alone. The neural basis of auditory fear conditioning has been extensively studied. The canonical circuit of auditory fear conditioning involves transmission of auditory information from auditory thalamus and cortex to the lateral amygdala, where it converges with somatosensory information. Combining tracing with electron microscopy, researchers identified a novel pathway from LA to ACx (Figure A). Using chemogenetic and optogenetic techniques, they showed that selectively silencing LA-ACx pathway could largely abolish fear responses (Figure B), indicating that this pathway plays a key role in fear memory.

  To examine whether fear learning could induce structural plasticity of LA-ACx pathway, researchers performed long-term in vivo two-photon imaging in mouse ACx to investigate structural changes of presynaptic LA axon boutons and postsynaptic ACx dendritic spines after fear conditioning. They found that formation of LA boutons and spines of L5 neurons in ACx both increased significantly at 3 days after conditioning (Figure C). By contrast, no changes were observed in anterior cingulate cortex or medial geniculate axon boutons, or spines of L2/3 neurons in ACx, suggesting that fear learning could induce specific synaptic changes in LA and ACx L5 neurons.

  Spines on the same dendrite and boutons on the same axon could form synapses with different neurons. It is thus of interest to determine whether the turnover dynamicsof boutons and spines were differentially modulated in a pathway-specific manner. To address this question, researches for the first time used dual-color two-photon imaging in live animals. By expressing different fluorescent proteins in pre- and postsynaptic neurons, researchers identified putative synaptic  contacts in a defined pathway. They found that formation rates of boutons and spines in LA-ACx connections were significantly higher than average after fear conditioning (Figure D), indicating that  synaptic plasticity is pathway-specific. Furthermore, fear conditioning induced a rapid and long-lasting elevation in the formation of new LA-ACx connections (Figure E), consistent with the rapid formation and long-term consolidation of fear memory.

  Using dual-color imaging, researchers found that new synaptic pairs were essentially all due to either adding a new spine to an existing bouton or a new bouton to an existing spine (Figure F), with extremely rare occurrence of de novo synapse formation. This form of synapse formation is less demanding for synaptic space and resources, and is observed in all synaptic connections in this study, thus is possibly a general rule for synapse remodeling in the adult brain.

  In this study, Yang, Liu et. al discovered that the LA-ACx pathway plays an essential role in fear memory, and found specific structural remodeling associated with fear learning. This study provided a new method for studying pathway-specific structural plasticity, added to the neural basis underlying fear learning, and proposed a rule for synapse formation in the adult brain.

  This work entitled “Selective synaptic remodeling of amygdalocortical connections associated with fear memory”was published online in Nature Neuroscienceon September 5, 2016.YANG Yang and LIU Danqian are the first authors with equal contribution.