It is well
established that the hippocampus is central for learning and memory, encoding mnemonic
data about past experiences and connections. However, the role of the
hippocampus in emotional processes is less clear, although there have been
inklings of evidence in the past suggesting that the hippocampus does indeed
play a role in fear and anxiety.
Perhaps the link between the hippocampus and anxiety can be best seen in human cases of trauma, where previous traumatic experiences are encoded in memory (likely in the hippocampus). This memory can contribute to an individual’s tendency to associate specific contexts or cues with the traumatic experience. In a more pathological case, this association can become overly generalized, where the individual tends to associate fearful experiences with general context and cues in daily life.
This high anxiety condition is known as post-traumatic stress disorder (PTSD); a prevalent psychological problem among the 2 million returning U.S. troops from Iraq and Afghanistan, as well as other war veterans. To improve this situation, scientists are keen on understanding what causes PTSD following exposure to threatening situations in combat, as well as past traumatic experiences.
A recent work by Dr. René Hen, at the Columbia University in New York, unveiled a rare neurological insight into how past traumatic experiences or frightening memories are translated into the hippocampus, and how anxiety is produced. Hen’s study is the first step into understanding the precise neurological framework behind PTSD, empowering scientists with mechanistic insights on how one might prevent PTSD, or provide more effective treatments at the onset of PTSD.
In her recent publication in a March, 6, 2013 issue of Neuron, Hen described a transgenic mouse model that is engineered to express a light receptor (opsin) specifically in the hippocampus. Mouse strains are engineered to express either the stimulatory or inhibitory opsins in the hippocampus, which then respond to light exposure (delivered via optical fibers) by activating or suppressing neuronal activity respectively. The system was then used to evaluate how each region in the hippocampus is responsible for encoding traumatic experiences and regulating anxiety.
Much like the U.S. troops in Iraq who are routinely bombarded with threats, the rodent recruits in Hen’s study were likewise exposed to bodily threats (such as a light foot shock) typically following a designated cue or context. This type of training is dubbed fear conditioning, which causes the mice to automatically show a fearful response (such as its freezing behavior) to a designated cue/context.
Using various optic-fiber directed illumination patterns to control the neuronal activity along selected regions of the hippocampus, Hen showed that the dorsal region of hippocampus is responsible for encoding cues or contexts associated with foot shock, and that light-induced suppression, or excessive activation, of this region impaired the fear encoding process. The excessive activation is thought to cause interference in nerve transmission, thus suppressing the normal fear encoding in the dorsal hippocampus. In contrast, light induced activation of the ventral hippocampus suppressed the fearful behavior in mice, suggesting that the ventral region is largely responsible for suppressing innate anxiety; an effect likely triggered by activating neuronal connections leading to the amygdala (an emotion processing center in the brain).
The study suggests that human’s previous traumatic experience is likely to be encoded in the dorsal region of the hippocampus, allowing the individual to associate the traumatic experience with designated context or cues. On the other hand, the ventral hippocampus may work to suppress anxiety in response to frightening memories.
Hen’s study further implies that dorsal region of the hippocampus is a neurological framework behind the onset of PTSD, and that the ventral region is simply to suppress PTSD symptoms of anxiety. Because the activation of the ventral hippocampus solely suppresses anxiety without impacting memory formation, stimulation of the ventral hippocampus may therefore prove to be a highly feasible treatment for PTSD in the clinic.
Finally, it can be said that Hen’s discovery is a major breakthrough in our understanding of how past traumas are encoded into frightening memories and connections in the hippocampus, and how anxiety is produced. Before Hen’s study, the hippocampus has always been considered the iconic brain structure for learning and memory formation, and that its role in anxiety/fear processing was considered a minor role based on the little data available in that respect. With Hen’s work, the hippocampus is now in the forefront of our understanding of how the brain remembers and responds to fear; a neurological framework for scientists to dig for mechanistic insights behind the development of PTSD, and how this disorder can be effectively treated.
Kheirbek, M.A., Drew, L.J., Burghardt, N.S., Constantini, D.O., Tannenholz, L., Ahmari, S.E., Zeng, H., Fenton, A.A., and Hen, R. Differential Control of Learning and Anxiety along the Dorsoventral Axis of the Dentate Gyrus. Neuron 77, 955–968, March 6, 2013. http://dx.doi.org/10.1016/j.neuron.2012.12.038