BLA to vHPC Inputs Modulate Anxiety-Related Behaviors

• Published in: Neuron (Cambridge, Mass.) Vol. 79; no. 4; pp. 658 - 664
• Main Authors: Felix-Ortiz, Ada C., Beyeler, Anna, Seo, Changwoo, Leppla, Christopher A., Wildes, Craig P., Tye, Kay M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.08.2013; Elsevier Limited
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Amygdala - physiopathology; Animals; Anxiety; Anxiety - genetics; Anxiety - pathology; Bacterial Proteins - genetics; Behavior; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics; Channelrhodopsins; Disease Models, Animal; Excitatory Amino Acid Antagonists - pharmacology; Experiments; Exploratory Behavior; Halorhodopsins - genetics; Halorhodopsins - metabolism; Hippocampus - cytology; Hippocampus - physiopathology; In Vitro Techniques; Luminescent Proteins - genetics; Male; Maze Learning; Membrane Potentials - genetics; Membrane Potentials - physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Pathways - physiology; Neurons; Neurons - physiology; Rodents; Sodium Channel Blockers - pharmacology; Studies; Synapses - physiology; Tetrodotoxin - pharmacology; Valine - analogs & derivatives; Valine - pharmacology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2013.06.016

The basolateral amygdala (BLA) and ventral hippocampus (vHPC) have both been implicated in mediating anxiety-related behaviors, but the functional contribution of BLA inputs to the vHPC has never been directly investigated. Here we show that activation of BLA-vHPC synapses acutely and robustly increased anxiety-related behaviors, while inhibition of BLA-vHPC synapses decreased anxiety-related behaviors. We combined optogenetic approaches with in vivo pharmacological manipulations and ex vivo whole-cell patch-clamp recordings to dissect the local circuit mechanisms, demonstrating that activation of BLA terminals in the vHPC provided monosynaptic, glutamatergic inputs to vHPC pyramidal neurons. Furthermore, BLA inputs exerted polysynaptic, inhibitory effects mediated by local interneurons in the vHPC that may serve to balance the circuit locally. These data establish a role for BLA-vHPC synapses in bidirectionally controlling anxiety-related behaviors in an immediate, yet reversible, manner and a model for the local circuit mechanism of BLA inputs in the vHPC. •Optogenetic inhibition of BLA-vHPC projections reduces anxiety•Optogenetic activation of BLA-vHPC inputs is sufficient to increase anxiety•In vivo and ex vivo evidence shows glutamatergic inputs are monosynaptic•BLA influences vHPC pyramidal cells via direct excitation and indirect inhibition Felix-Ortiz et al. explore the interaction between the amygdala and other brain regions, assessing the functional contribution of basolateral amygdala inputs to the ventral hippocampus during anxiety-related behaviors in mice. They demonstrate bidirectional modulation of anxiety-related behaviors by these inputs.