Role for the Claustrum in the Emotional Regulation of Behavior
Molecular Neurobiology Lab, Xin Jin
Salk Institute for Biological Studies
San Diego, CA
My interest to gain a neurobiological understanding of anxiety, depression, and substance abuse, led me to explore the brain regions associated in emotional processing. Therefore, I started experimenting with the claustrum (CLA), secondary motor cortex (M2), and amygdala to investigate how the fear circuitry modulates behavior, specifically movement. By using tracing techniques, we found projections from the BLA intermingle with CLA projection neurons that target the M2 cortex, ultimately demonstrating a pathway capable of gating movement due to emotional valiance. I became curious of this connection and behavioral output, so I tested ablation and optogenetic methods while animals perform elevated plus maze, auditory fear conditioning, intracranial self-stimulation, and real time place preference. Interestingly, upon ablation of the CLA via diphtheria toxin, mice exhibited exploratory behavior and a reduced freezing response to the auditory cue that predicted a foot shock. Additionally, mice undergoing optogenetic stimulation of the CLA demonstrated a preference for the non-stimulated side in RTPP and showed no preference towards the “active” lever in ICSS. These preliminary findings indicate the connection from claustrum to M2 may gate a fear response that is implicated in prevalent neuropsychiatric disorders.
Role for claustrum in the emotional regulation of behavior. (A) Anatomical validation of BLA —> CLA—> M2 pathway via retrograde (AAVretro.cre) and CTB tracers. (B) Strategy for cre-dependent diphtheria toxin based cell ablation of claustrum. Examples of GFP and NeuN staining in lesion (top) and control (bottom) animals. (C) Schematic and data demonstrating diphtheria-lesioned animals exhibit an anxiolytic phenotype during elevated plus maze and auditory fear conditioning. (D) Schematic of viral targeting strategy paired with representative example of cre-dependent ChR2-mCherry expression and location of optical fiber over CLA. (E) Data for optogenetic-based Real Time Place Preference reveals CLA-ChR2+ mice avoid stimulation side of paradigm.
Jared B. Smith, Roy Kim, Sho Aoki, Nick Hollon, Jason Klug, Hao Li, Elora Williams, Jazlene Mallari, Jin Yi Wu, Aiden Jauffret, Xin Jin