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Today, I’m starting a new feature here at chrisdellavedova.com - trying my hand at scientific writing for a lay audience. Each week I’ll try to distill an article or two from one of the big scientific journals. This new theme corresponds a bit with a recent post about career goals, so I would be eternally grateful for any comments regarding the Science Tuesday feature - critical or complimentary.I’m a plant geneticist by trade, but this week what caught my eye were two papers describing research into what’s going on in the brain. First, an article in Nature looking at the genetic basis of obsessive compulsive disorder (something that both Dr. O’C and my friend Martha tell me that I suffer from) and second, a paper from Science with a very interesting approach into studying the primal nature of fear.Obsessive compulsive disorder (OCD) is a psychological condition related symptomatically to other anxiety disorders. It is characterized by recurrent, persistent thoughts, images and feelings that are usually unwelcome (obsessions) and repetitive behavior (compulsions). OCD affects, in varying degrees of severity, roughly two percent of the population. While in its milder manifestations, it can be merely a nuisance, severe cases of OCD require treatment such as therapy, medication or, in extreme cases, hospitalization. This week’s Nature featured research from a collaboration of researchers from Duke University (USA), Zhejiang University (China), University of Coimbra and Gulbenkian Science Institute (Portugal) and the University of North Carolina (USA) focusing on a gene that seems to bear some responsibility for preventing OCD.It is fairly well established that OCD is a genetic disease that is passed down through families. For example, immediate family members of OCD patients are up to 12 times more likely than the general public to suffer from the disease,which demonstrates that it runs in families. In twin studies, identical twins (who are genetically identical) are 80% likely to have both twins suffering from OCD where fraternal twins (50% genetic identity) are only 50% likely to have both twins suffering. However there has never been a firm link established between defects or mutations in a particular gene and OCD symptoms. The work that Welch and his colleagues describe identifies a genetic mutation that results in OCD symptoms in mice.To understand this work we need a little primer on neurobiology. Synapses are basically the junction between nerve cells (neurons) which allow them to form a network throughout the body. Communication between neurons and between neurons and muscular cells for example are controlled by neurotransmitters, chemicals which move across these junctions. For neurons to communicate with each other, the biochemical makeup of these synapses must be maintained.The research described involved a mutation of Sapap3, a gene which codes for a protein component of the neuron near the synapse. When this gene is deleted, mice exhibited behaviors reminiscent of human OCD including excessive grooming, increased anxiety and response to certain drugs used to treat OCD. For example, mice missing Sapap3 were up to seven times more likely to develop lesions due to continuous facial grooming than siblings that have a functional copy of the gene. Certain types of antidepressants (selective serotonin reuptake inhibitors) have been shown to be effective in the treatment of OCD. When mice lacking Sapap3 were treated with fluoxetine (the generic version of Prozac) for six days, this compulsive grooming was reduced to normal levels, whereas the drug had no effect on normal mice.Sapap3 is found most abundantly in a part of the brain called the striatum. Defects in neural circuitry in this region of the brain has been implicated in OCD. Thus, the researchers looked for defects in transmission or in the shape of the synapses in mice with the deletion. There is a significant reduction in signaling between neurons in brains of the mutated mice. However, there are only minor changes in the structure of synapses in mice with the deletion. This result gives biochemical evidence which essentially says there is a bad connection in this part of the brain when Sapap3 is absent.As a geneticist, the best way to prove that a mutation in a gene is responsible for a disease is to cure the disease by fixing the mutation, in this case adding the gene back to mice which are missing Sapap3. The researchers do this in a very convincing way by injecting the Sapap3 gene fused to a gene coding for a flourescent protein (GFP). The presence of GFP allows researchers to see where the gene is being expressed. Mice with the deletion in which the Sapap3 gene was turned on transgenically near synapses in the striatum (right place and right time) showed reduced anxiety and reduced skin lesions. This demonstrates definitively that the Sapap3 gene is responsible for maintaining a synaptic connection which, when lost, can result in OCD like symptoms. This work for the first time, isolates a gene which is responsible for OCD thus opening doors for further research into treatments for the disorder.——————————————————————Fear is a strange thing. It’s primal and in many cases instinctual response to the perception of imminent pain or danger. Scientists that study behavior have found that many animals respond to fear in similar ways and that the response has much to do with just how close danger lurks. When a threat is perceived at a distance, a predator skulking along the horizon, the animal responds with a part of its brain that is used for planning complex strategies of avoidance. In other words, the animal thinks “logically” about options. However, when an attack is imminent - when the predator is poised to strike - activity in the brain shifts to a more primitive part of the brain that controls instinctual behavior. Do you fight, run or freeze?What was unknown was whether or not humans respond in similar ways to other animals. Many people think that humans have lost a lot of survival instincts that are maintained by other animals. Researchers at University College London took a very interesting approach to this question and the results were reported in this week’s Science magazine. Using remarkably tolerant volunteers, Mobbs and colleagues tested the hypothesis that humans do retain this instinctual fear response. Volunteers were subjected to an active “escape-pain” task that works something like this. Subjects were given a series of computer mazes to navigate. They were allowed to wander for a few seconds, then chased by a virtual predator for varying times (16 to 32 seconds). If the subject escaped the maze without being caught nothing they were allowed rest. If the subject was captured by the predator, after a couple of seconds they were given either three (high intensity) or one (low intensity) shocks. This is potentially the coolest experimental design I’ve ever heard of and one that immediately summons the story of Theseus and the Minotaur.To establish the response in the brain, magnetic resonance imaging (MRI) was used to scan the brain and activity was measured be following blood oxygen levels in different regions of the brain. What the researchers found is that humans do indeed maintain the instinctual responses to danger that are found in other animals. During the chase phase, the time in which the subjects were navigating the maze, most of the brain activity was in the cerebellum and other regions required for complex decision making and motor activity. In other words, subjects were thinking quickly trying to escape from the maze. However, after capture, when pain was imminent, activity was focused in the periaqueductal gray - the primitive region of the brain that in other animals is the zone responsible for the freeze, flee or flight response. Importantly this was the case whether or not the subjects were given a shock so they were responding to fear, not pain.So we may be highly evolved and may have lost a lot of animal instincts, but when it comes to primal responses we react just like that deer in headlights.Credits:Aligned pastaNeuronsGFP neuronsTheseus and the Minotaur