HAIFA, Israel (Press Release) — A new study from the University of Haifa has identified specific neutral pathways that create an exaggerated reaction to perceived threats following a traumatic event. The study was recently published in the prestigious journal Nature Communications.
“The identification of these pathways is important for our understanding of the specific changes that take place in the brain following an extreme adverse event. The brain is unique in that it changes constantly, for example when we learn. An extreme adverse event may create very strong learning associated with irreversible changes in the brain, leading to inflexible and maladaptive behaviors,” explains Dr. Oded Klavir from the School of Psychological Sciences, the author of the study.
Interest in post-traumatic stress disorder (PTSD) and its various ramifications has increased following the “Iron Swords” war. Various events may cause traumatic memories to resurface many years after the initial trigger event, disrupting the lives of those who suffer from PTSD.
The current study was undertaken by a research team at Dr. Klavir’s laboratory that included research students Shlomi Habusha and Lior Givon and laboratory director Dr. Shahaf Edut, and was led by research student Dr. Ami Ritter of the School of Psychological Studies at the University of Haifa. The team sought to examine the changes in the brain’s information transfer that lead to an exaggerated reaction of fear in response to a traumatic event.
In the first stage of the study, the researchers placed a mouse at one end of an elongated arena and a robotic toy beetle that did not pose any threat to the mouse at the other end. They monitored various aspects of the mouse’s behavior in response to the beetle. In the second stage, they put the mouse in the same arena with the same robo-beetle one week after the mouse experienced a significant traumatic event. The researchers observed a dramatic change in the mouse’s behavior, both in general and toward the robo-beetle.
The mouse was more inclined to escape the robo-beetle and even began to keep a greater safety distance from the beetle than it had done before experiencing trauma. This change in behavior was stable for at least three weeks following the trauma. In order to identify the change in the brain that caused the mouse to alter its perception of the threat and to increase its safety distance from the perceived danger, the researchers recorded the activity of the neurons in the superior colliculus, a relatively primal area that receives information directly from the retina and accordingly can rapidly cause movement in response to visual stimulation – in mice, for example, this will be manifested in escape from a visual threat.
The researchers understood from the recordings that the neurons in this area usually respond within a few milliseconds before the escape. “Following the traumatic event, we found that the neural activity takes place earlier before the escape, and when the distance between the mouse and the robo-beetle is greater, which could promote the escape behavior, thereby increasing the safety margin,” the researchers note.
In an attempt to understand where the change occurs in the neutral circuit that causes these cells to respond more rapidly, the researched mapped the areas that directly influence the superior colliculus. Using a method called “opto-genetics,” they engineered the neurons in these areas and caused them to be activated by light. By illuminating the superior colliculus and activating the engineered cell projections, the researchers could track the specific input source that activates the cells whose activity changed following the exposure to trauma. The results indicated that it is a cohort of specific escape responsive cells in the superior colliculus which change their activity significantly afore the escape onset, following exposure to a traumatic event. These cells receive the information that activates them from the medial prefrontal cortex, a relatively recent evolving area, responsible for the integration of information and for emotional regulation. “The cells we discovered in the study send their projections to the superior colliculus both directly and through a group of nuclei called the basal ganglia that plays a role in selecting and prioritizing actions,” Dr. Klavir explains.
To determine whether change in these cells is necessary in order to create change in the safety margin and perception of threat, the researchers used chemogenetic tools to turn off only those cells in the medial prefrontal cortex that have the bifurcating influence on the escape cells in the superior colliculus during the traumatic event. The results show that the increase the safety margin following adversity disappeared, in contrast to mice in which these cells were not turned off during adversity. The researchers concluded: “this result shows that the function of these cells is necessary for inducing the ‘trauma’ effect on the safety margin.”
In the next stage, the researchers activated the same cells optogenetically , this time in mice that had not undergone the traumatic experience. They found that the activation of the cells in the medial prefrontal cortex that have the bifurcating effect on the escape cells in the superior colliculus activates the escape behavior as a function of the distance from the robo-beetle at which the cells were activated. In other words, the activation of this system is sufficient to induce the safety margin at which the escape behavior from a visual threat is activated.
What are the practical ramifications of the identification of these mechanisms? Dr. Klavir notes that at present, the usual treatments for traumatic memories are inefficient in attenuating the associations that raise these memories, since they were forged during a powerful emotional experience. Understanding the mechanism and the localization of the specific cells and synapses where the change occurs may one day facilitate diagnosis and advance the development of techniques for repairing and reversing identifiable maladaptive associations.
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Preceding provided by the University of Haifa