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.
Reference:
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.
