Tipping the Neurological Scales

Even from an early age, we all pick up basic lessons on the cues of the world. Hot stove = bad. Petting puppy = good. When something falls into a general category like this, we can define them by calling them ‘emotional memories’. These are memories that have an emotional valence, or direction to them. Remembering the way Sparky loved his belly rubs makes you happy, so this memory has a positive valence. Interestingly, these emotional memories actually process themselves differently in the brain. Different valences light up different brain regions and use separate chemicals to pass the message along. In addition to coming in a wide range of feeling, emotional memories also come in varying strengths. Strong emotions, ones that might put you on top of the world or even shake you to your core, these stick around pretty stubbornly in the brain, and they link themselves to physical body changes too. Our shoulders may tense up when we get anxious, or our ears may get hot when we’re embarrassed. These learned behaviors get firmly rooted in our brain the more we are exposed to the same situation that caused them, resulting in learned physical behaviors directly linked to a trigger. This strong tie to emotional memories is part of the root for PTSD and addiction.

Dr. Do Monte and his student examine rat brains

Dr. Fabricio H. Do Monte is a professor in the department of Neurobiology and Anatomy at UTHealth studying exactly how these emotional memories are tied to specific brain circuits and chemicals, then using that knowledge to hopefully find ways to treat deficiencies. Dr. Do Monte uses rats to help him understand the human brain, because rats have very similar neural structure to humans, using the same neurotransmitters and framework to establish memories. One method that Dr. Do Monte utilizes is memory implantation; not quite Inception level, but still pretty cool. Basically, every time a long beep plays, the rat receives a little shock to the foot. Nothing that would hurt them, its more like touching your tongue to a battery that way all of our grandpas used to make us do. Everyone else’s grandpa did that, right? Beep, shock. Beep, shock. Now the rat learns to be anxious of the noise, because it learned the association. After a while, you can play the beep without the shock and still see the rat tense up as he prepares for what he learned comes next. This is emotional memory association, and it is very similar to why veterans of wars have severe reactions to loud explosive noises like fireworks. Dr. Do Monte then examines ways of blocking these responses, such as by using medications or reconditioning.

With a technique called extinction therapy, a stimulus that already has a programmed response (beep means shock) is repeatedly introduced, but with a new meaning. If the beep is played a hundred times, but the rat gets a treat every time instead, this can change the direction of the implanted memory towards something good. This repeated exposure with a new meaning changes the valence of the memory. Soon enough, the rat loves the beep. Luckily, both rats and our brains are stretchy and bendy enough to go back and forth between valences like this, so these treatments can be fairly effective.

In a broader sense, there are so many situations every day where we balance good rewards and bad consequences. Do I indulge myself in that creamy cheesecake even though it goes straight to my hips? Do I watch the scary movie even though I know I won’t sleep? This balancing act requires the fear and reward centers of the brain to work together to weigh our options and accurately measure the impact that our actions have. In someone who shows signs of addiction, one side of the scale may be a little wonky, so that person can’t really get a sense of the consequences of their actions. They legitimately cannot fathom how bad something may turn out, because their negative learned memories may not be as easy to imprint or recall. Dr. Do Monte and his team can model this by exposing a rat to cat sounds and smells while simultaneously offering them treats. Fear of predators is an innate memory, one that they are born with. In this situation where there is a direct good thing and a direct bad thing, the rats freeze up. They stop to consider their options and visibly ponder their next move. Is the food worth being Coco’s afternoon snack? The team can isolate which parts of the brain contribute to each side of the balance and then use various tools, such as the optogenetics covered in a previous article, to sway the rat in one direction or another.

A rat exposure tank, complete with sight, sound, smell, taste, and touch. A sensory buffet for our little friends.

A newly developing project uses rats who have been developed to be symptomatic models of morphine addicts. These rats may spend all of their little rat brain energy concentrating on how awesome a drug is to them, and the consequence center of their brain is less used. If you put morphine in front of them, they will gladly consume it, regardless of how many times you sit them down and explain to them how bad it is for their health and how their little rat family is falling apart. However, when Fabricio and his team activate the balancing act of the brain, the rats immediately lose interest. Drop of a hat, the addiction is gone. It’s stunning how tightly linked the neurological imbalance is tied to even extreme behaviors and is hopefully indicative of future treatments.

By studying these rats and their memory systems, Dr. Do Monte and his team hope to breathe new life into addiction studies, reducing the invasiveness of brain manipulation and increasing the effectiveness of treatments. His lab’s work may impact millions of people around the world who struggle with PTSD, addiction, eating disorders, and many other imbalance issues. If people are as receptive as the rats to these treatments, I’d say that the future of these technologies is very optimistic.

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