Fear learning modifies circuits in the central amygdala.
Fear is a fundamental adaptive mechanism that occurs throughout the animal kingdom – even a sea slug (Aplysia) can learn to produce a conditioned fear response. In humans our fears can be complex and varied. In conditions such as post-traumatic stress disorder (PTSD) a highly traumatic event can set off "too much" fear after the initial trauma has passed. Symptoms of PTSD include flashbacks and nightmares, memory avoidance and hypervigilance, all of which can prevent suffers from leading healthy, productive lives.
Researchers from Cold Spring Harbor Laboratory, led by Associate Professor Bo Li, have been looking into the neural circuitry underlying fear memory and expression. Their research, in two papers published in Nature Neuroscience (2013) and The Journal of Neuroscience (2014), used electrophysiology and optogenetic techniques to elucidate the complex neural circuitry involved in how fear is learned, controlled and expressed. The research was carried out using the Scientifica PatchStar micromanipulator, the Molecular Devices Multiclamp amplifiers, pCLAMP software, and a CoolLED single wavelength LED system.
In 2013, Bo Li and his team determined the precise neurons in the central amygdala that control fear memory. The team used Pavlovian conditioning to train mice to show fear behaviour (freezing) in the presence of a tone. They then monitored excitatory synaptic transmission onto different classes of a lateral subdivision of the central amygdala (CeL) neurons. Simultaneous recorded pairs of SOM+ (self-organising map) and an adjacent SOM- in the CeL in acute brain slices showed that fear conditioning strengthened excitatory synapses onto SOM+ neurons while weakening those onto SOM- neurons in the CeL. SOM+ and SOM- CeL neurons exhibit mutual inhibition. The fear conditioning introduced a bias in the competition between these two groups of cells so that SOM+ neurons were preferentially activated. These activated SOM+ neurons were sufficient to release the freezing fear response.
The group then used the optogenetic technique of introducing channelrhodopsin-2 (ChR2) expressing in lateral amygdala neurons via viral injection. They found that light activation of the lateral amygdala reliably produced excitatory synaptic transmission onto CeL neurons. The result is consistent with the existence of an anatomical connection from lateral amygdala to CeL.
New research published this year builds on previous work providing an understanding of how the central amygdala communicates fear memories to the areas of the brain responsible for action. They found that a group of long-range neurons extend from the central amygdala and project to the midbrain periaqueductal gray (PAG) area of the brainstem. It is this area of the brainstem that controls the fear response.
Understanding these mechanisms of fear learning and expression could eventually lead to better treatments for PTSD and other anxiety disorders.
Paper details:
Haohong Li, Mario A. Penzo, Hiroki Taniguchi, Charles D. Kopec, Z Josh Huang & Bo Li (2013) Experience-dependent modification of a central amygdala fear circuit. Nature Neuroscience: 16, 332–339. doi:10.1038/nn.3322 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581751/
Mario A. Penzo, Vincent Robert, and Bo Li (2014). Fear Conditioning Potentiates Synaptic Transmission onto Long-Range Projection Neurons in the Lateral Subdivision of Central Amygdala. The Journal of Neuroscience: 34(7): 2432 – 2437 doi: 10.1523/JNEUROSCI.4166-13.2014 http://www.jneurosci.org/content/34/7/2432.abstract
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