Author: Diya Chutani

  • Rating Neurotransmitters by (Personal Preference?)

    What is a neurotransmitter? 

    Neurotransmitters are the chemical messengers used for communication between neurons. They are released into the synapse (gap between neurons) by the neuron referred to as the presynaptic neuron and then cause some sort of response (generally excitatory, inhibitory, or modulatory) on the postsynaptic neuron (Hook et al, 2019). 

    Some traditionally recognized neurotransmitters include serotonin, dopamine, and adrenaline.

    However, the scope of what a neurotransmitter is has been expanding to include a broader range of signaling chemicals. Now, substances like Nitric Oxide (NO) and ATP (yes, adenosine triphosphate, the one made in the powerhouse of the cell) are beginning to be included as well. 

    Now let’s make a tier list…

    For the purposes of this list, we will be focusing on some of the more traditional neurotransmitters.

    Serotonin

    To start off, we’ll go with one that is pretty well known: serotonin. This monoamine is involved in the signaling for a huge variety of systems including regulation of mood, sleep, digestion, and more. It is commonly associated with depression and a common treatment for depression for decades has been SSRIs (Selective Serotonin Reuptake Inhibitors) which essentially stop processes that clear serotonin from the synaptic cleft (Preskron, 1997). So serotonin is pretty cool, pretty popular, and I guess with it being linked to our ability to be well, not depressed, it should be pretty high up. 

    But to put it in the S tier feels too basic. And recent advances in depression treatments support a new theory of depression involving a different neurotransmitter (more on this coming soon). So I say serotonin gets a solid A. 

    Acetylcholine

    Acetylcholine is one of my personal favorites. It’s most commonly known for being used by pre synaptic neurons at the neuromuscular junction which is where nerve meets muscle. This means the release of acetylcholine is essential for movement. My favorite acetylcholine fact is that botulinum toxin can be used to inhibit its release at these junctions which is actually what botox does (Nigam, 2010). Can’t wrinkle if those muscles can’t move. I’m giving acetylcholine an A!

    GABA

    Ah, the primary inhibitory neurotransmitter in the central nervous system. Inhibition is so important and honestly quite underrated. Without GABA, there would be too much activity which  could lead to a whole host of consequences. Low GABA levels are linked to diseases like epilepsy, motor disorders like stiff person syndrome, and even schizophrenia (Levy & Degnan, 2013). And of course, this inhibition is also crucial for sleep which is a personal favorite activity of mine. So, for the essentialness of inhibition, I think we have our first S tier neurotransmitter.

     

    Epinephrine 

    I may or may not be wearing my epinephrine (aka adrenaline) necklace as I write this; however, I can not say I am a huge fan of this molecule, at least, not as a neurotransmitter. It’s associated with sympathetic nervous system activity which is the part of our autonomic nervous system that responds unconsciously to stressful situations, often referred to as the fight or flight response (C.C medical). When epinephrine is released in my body, I generally want to get out of whatever situation I am in. I almost want to put this guy in D tier, but I guess the responses in my body due to epinephrine helps me get out of that situation so I’ll cut it some slack and put it in C. 

    Norepinephrine 

    Norepinephrine (Noradrenaline) is also involved in that fight or flight response and is generally important for arousal and alertness (Tank, 2015). I’m going to go ahead and put this one near its very chemically similar friend epinephrine in the B row. 

    Glutamate 

    Now we have our primary excitatory neurotransmitter (the anti-GABA). Glutamate is essential for learning and is believed to be essential in neuroplasticity (aka our brains ability to change which is very cool). Recently, glutamate has been theorized to have a role in depression and ketamine is being utilized as a way to treat treatment resistant depression (Pal, 2021). The results are very impressive and cause long term positive impacts from small doses. I like learning and I like treating depression, so S tier! 

    Dopamine

    Ok, I admit, I have a favorite. Dopamine is extremely important and one of the key processes it is involved in is motivation (Olguín et al, 2016). Its role in reward makes it an important molecule in guiding our behaviors as the presence of dopamine is associated with pleasurable feelings. It is also involved in movement; Parkinson’s disease, a movement disorder, is actually attributed to a decrease in dopamine production in a region called the substantia nigra.

    In my eyes, dopamine is a great example of the complexities of the nervous system because it has involvement in multiple systems and its dysregulation can have a huge range of impacts. Its association with pleasurable feelings displays how in moderate amounts dopamine offers positive feelings but in excess we see how it can become harmful like in the case of addictions. So with that I say, S+ tier!!! 

    To sum it up…

    While creating this list, I thought long and hard about how to compare these neurotransmitters and found myself using the approach of, ‘which one could be removed’. The answer: none of them. Each of these neurotransmitters is involved in multiple systems and some dis-regulation of them can cause widespread consequences. So to completely remove any neurotransmitter would be detrimental. This demonstrates how fine tuned our brains are to function in a way where the production and use of neurotransmitters is precise and modulated. All this to say the rankings of these neurotransmitters was quite arbitrary and are based essentially on just my own opinions, but I hope you learned a little bit about the epic chemicals that allow neurons to communicate along the way! 

     

    References

    C. medical. (n.d.). Epinephrine (adrenaline): What it is, function, deficiency & side effects. Cleveland Clinic. https://my.clevelandclinic.org/health/articles/22611-epinephrine-adrenaline 

    Hook, V., Kind, T., Podvin, S., Palazoglu, M., Tran, C., Toneff, T., Samra, S., Lietz, C., & Fiehn, O.. (2019). Metabolomics Analyses of 14 Classical Neurotransmitters by GC-TOF with LC-MS Illustrates Secretion of 9 Cell–Cell Signaling Molecules from Sympathoadrenal Chromaffin Cells in the Presence of Lithium. ACS Chemical Neuroscience, 10(3), 1369–1379. https://doi.org/10.1021/acschemneuro.8b00432

    Juárez Olguín H, Calderón Guzmán D, Hernández García E, Barragán Mejía G. The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress. Oxid Med Cell Longev. 2016;2016:9730467. doi: 10.1155/2016/9730467. Epub 2015 Dec 6. PMID: 26770661; PMCID: PMC4684895.

    Levy, L. M., & Degnan, A. J.. (2013). GABA-Based Evaluation of Neurologic Conditions: MR Spectroscopy. American Journal of Neuroradiology, 34(2), 259–265. https://doi.org/10.3174/ajnr.a2902

    Nigam, P. K., & Nigam, A. (2010). Botulinum toxin. Indian journal of dermatology, 55(1), 8–14. https://doi.org/10.4103/0019-5154.60343

    Pal M. M. (2021). Glutamate: The Master Neurotransmitter and Its Implications in Chronic Stress and Mood Disorders. Frontiers in human neuroscience, 15, 722323. https://doi.org/10.3389/fnhum.2021.722323

    Preskorn S. H. (1997). Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clinical pharmacokinetics, 32 Suppl 1, 1–21. https://doi.org/10.2165/00003088-199700321-00003

    Tank, A. W., & Lee Wong, D. (2015). Peripheral and central effects of circulating catecholamines. Comprehensive Physiology, 5(1), 1–15. https://doi.org/10.1002/cphy.c140007

     

  • Virtual Nature: Could it yield the same effects?

    I recently went on my first backpacking trip and was able to spend my time immersed in a natural environment. Among those trees and streams of water, I felt a sense of serenity and peace that I do not normally experience in my day to day life in Atlanta. I am not alone in feeling a relief and escape in nature. Research over the last couple decades has consistently demonstrated that time in nature has positive impacts on well being due to stress relieving benefits and increasing cognitive function (Berto, 2014). Environments with these benefits are often referred to as restorative environments and a recent focus in research on the therapeutic benefits of these environments has been an effort to recreate them within VR environments. 

    So far, the research seems promising. One study exposed participants to a forest nature environment and a neutral environment both utilizing virtual reality. The simulation utilized both visual and auditory sensory components. The natural environment exposure was found to lead to an increase in cognitive performance, lower perceived stress, and higher restorativeness when compared to the neutral environment (Mostajeran et al., 2023). However, in a review of 21 similar studies, the results across the board were more mixed. There is a generally observed decrease in negative effect from exposure to restorative VR environments, but this review noted limited positive affect (Frost et al., 2022). 

    Overall, where the research on VR based nature interventions seems to be lacking is in comparison between the VR exposure and physical immersion into a nature environment. A key component of VR design that this relates to is the idea of presence vs immersion. Immersion refers to the sensory environment created by the technology and is therefore a reflection of the technology itself. On the other hand, presence is more related to the psychological state of the user and how integrated they feel they are in the environment. Presence is more subjective and can be influenced by the perspectives and experiences of the user (Berkman & Akan, 2019). However, both of these factors influence each other and greater immersion can generally increase feelings of presence. In restorative therapies utilizing VR nature exposure, both presence and immersion are essential, but the immersion is likely lacking. 

    In nature exposure research, there is a general gap in exploring different sensory modalities. Much of the research is highly focused on visual components. Within VR, visual and auditory components are the easiest to replicate so VR technologies are limited in their scope of creating an immersive sensory experience. For example, a key sensory route of positive affect from nature exposure is olfaction. One study examined the impact of indoor plants on psychophysiological health and cognitive performance, and they looked at both visual and olfactory components of the stimuli. The results indicated that “visual, olfactory and combined stimuli all induced spontaneous neural oscillations related to relaxation or cognitive function, and significant changes in metabolic pathways associated with antidepressant, anti-inflammatory or neuro-protective effects were observed” (Li et al., 2024). Another study compared the effects of visual stimuli and olfactory stimuli in park and forest environments and their results suggested that olfactory stimulation may have a greater role in facilitating stress reduction than visual stimuli (Hedblom et al., 2019). 

    Overall, the multi-sensory experience seems to be key to reaping the benefits of restorative environments which is something VR environments are currently unable to replicate. Furthermore, VR exposures may be limited temporally. These interventions would provide a brief, non tangible escape from the environment of the regular lives of those in urban environments. But after the interventions, the environment that could be causing higher stress is still present. Looking at the bigger picture, VR interventions are a bandaid on a bullet hole solution to higher stress levels brought on from urbanization. To reach the root of this problem, it may be more effective to examine what could be done to the environments themselves. 

     

    So, how can we alter the environments we spend our time in to be better suited for stress reduction and increased cognitive function? Biophilic design!  

    Biophilic design is the idea of integrating the restorative elements of nature into buildings, cities, and public spaces. The ideas of biophilic design relate to the Biophilia Theory which emphasizes the importance of human interaction with nature on the basis of our evolution alongside it. In Kellert and Calabrese’s book, Biophilic Design: The Theory, Science, and Practice of Bringing Buildings to Life, they outline several key components of biophilic design: direct experience with nature, indirect experience with nature, and experience of space and place (Kellert & Calabrese, 2015). Furthermore, the goals of good biophilic design go beyond allowing people to experience nature in their everyday environments; they aim to also be sustainable both environmentally and economically. Kellert and Calabrese also emphasize experiencing nature through different sensory modalities as a key aspect of designing buildings and cities. One literature review examined evidence for the benefits of biophilic design on wellbeing and found that the direct exposure to nature and the presence of natural elements had the most significant positive impact (Gillis & Gatersleben, 2015). 

    One recent example of Biophilic design in action can be seen in the Living Building Project. This initiative aims to design buildings that are self-sufficient, have a positive impact on individuals interacting with them and with the natural systems involved, and that connect people with natural light, space, air, nature, and food (What is The Living Building Challenge, 2024). 

    Ultimately, more research is needed for both VR as a restorative approach and biophilic design. However, biophilic design provides a multi-sensory element that VR currently lacks and both increases the level of positive exposure and decreases the source of negative affect. The increased focus on use of VR in the context of nature based restorative therapies has its merits but with the current limitations and the overall unanswered question of if it could truly replicate experiences in nature remaining, it might be better to focus on alternative approaches that could be more effective like changing the environments people are already present and immersed in. 

     

    References:

    Berto, R.. (2014). The Role of Nature in Coping with Psycho-Physiological Stress: A Literature Review on Restorativeness. Behavioral Sciences, 4(4), 394–409. https://doi.org/10.3390/bs4040394

    Berkman, M. I., & Akan, E.. (2019). Presence and Immersion in Virtual Reality (pp. 1–10). https://doi.org/10.1007/978-3-319-08234-9_162-1

    Frost, S., Kannis-Dymand, L., Schaffer, V., Millear, P., Allen, A., Stallman, H., Mason, J., Wood, A., & Atkinson-Nolte, J. (2022). Virtual immersion in nature and psychological well-being: A systematic literature review. Journal of Environmental Psychology, 80, 101765. https://doi.org/10.1016/j.jenvp.2022.101765 

    Gillis, K., & Gatersleben, B.. (2015). A Review of Psychological Literature on the Health and Wellbeing Benefits of Biophilic Design. Buildings, 5(3), 948–963. https://doi.org/10.3390/buildings5030948

    Hedblom, M., Gunnarsson, B., Iravani, B., Knez, I., Schaefer, M., Thorsson, P., & Lundström, J. N.. (2019). Reduction of physiological stress by urban green space in a multisensory virtual experiment. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-46099-7

    Kellert, S. R., & Calabrese, E. F. (2015). The practice of biophilic design. https://biophilicdesign.umn.edu/sites/biophilic-net-positive.umn.edu/files/2021-09/2015_Kellert%20_The_Practice_of_Biophilic_Design.pdf 

    Li, Z., Zhang, W., Cui, J., Wang, L., Liu, H., & Liu, H. (2024). Biophilic environment with visual-olfactory stimuli contributes to psychophysiological restoration and cognitive enhancement. Building and Environment, 250, 111202. https://doi.org/10.1016/j.buildenv.2024.111202 

    Mostajeran, F., Fischer, M., Steinicke, F., & Kühn, S.. (2023). Effects of exposure to immersive computer-generated virtual nature and control environments on affect and cognition. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-022-26750-6

    What is the Living Building Challenge?. International Living Future Institute. (2024, April 5). https://living-future.org/lbc/