Project by: Farin Weinger (9th Grade)
Project Advisor: Daniel Li
Student(s)’s Advisor(s): Jessica Tan

Description of the Project: This project began in the second trimester during which I explored basic concepts in neuroscience. You can view the learnings from that project here. This trimester, I set out to focus on the specifics of how the brain responds to different types of psychoactive drugs. I will be looking further into the causes and results of addiction, and connecting that to what I have previously learned about neuroscience (specifically neurochemistry).

Final Product (e.g., documents, images, video, audio, poster, display, etc.):

Final Reflection on Learning:

Overall, this honors project has been amazing. I have enjoyed every second of it, and have found a new passion that I will continue to work on (I’m taking an online course over the summer on neuropsychology). Even though, it’s sad to end this project every good thing has to end eventually and I am glad that I did this.

Reflection from my poster:

This project has given me a new appreciation of science and a new understanding of my passion. I never knew how much I loved learning about neurology, and even though I knew I loved medicine this is a new part of medicine to love. I was able to connect different aspects of my research in different ways which challenged my thinking, but I am happy that I was able to overcome anything that made me frustrated. Despite focusing in on a very specific part of neuropsychology, I am now able to use the skills I’ve gained for my future scientific projects. I have loved this project, and can’t wait for another. 

Update on Progress from Weeks 1-3 (include any photos or video if relevant):

The first couple of weeks of this honors project have been beginning to understand how psychoactive drugs create the effects they are associated with. I especially enjoyed the “mouse party” simulation which gave general information about the neurotransmitters affected by various drugs (such as marijuana or cocaine). I thought this simulation was helpful, and it also reflected the original types of testing scientists did to try and gain a deeper understanding of the neurochemistry of addiction. I learned that the more addictive types of drugs affect dopamine receptors/neurotransmitters (these consist of heroin, cocaine, methamphetamine, and marijuana). While each different drug has differing levels of addictive behaviors, these are considered to be the more addicting drugs because of their connection to dopamine. Dopamine is the neurotransmitter that is the most important to the reward pathway (connection from the VTA (origin of dopamine) to the nucleus accumbens (processes rewarding behavior) to the prefrontal cortex), and motor control. There are 5 different types of dopamine (D1-like and D2-like: D1 are excitatory and D2 are inhibitory), and drugs with inhibitory receptors are connected to overdose. Most of the drugs that I learned about were connected to dopamine, others were connected to serotonin (the “happiness” neurotransmitter) or other less connected  neurotransmitters (such as GABA (main inhibitory neurotransmitter) and glutamate (main excitatory neurotransmitter) which are connected to alcohol).

As I began to delve deeper into the nuances of drug use, I developed an interest in the cause and effect of addiction. This has become a bigger focus for my honors project. I have been reading scientific papers on the neurochemistry of addiction and how epigenetics/environmental pressures affect how susceptible someone is to addiction. I’ve learned that epigenetics and social situations are greatly connected. Different gene variation is one of the causes of a higher risk of addiction from certain substances. For example, the alpha 5 subunit of the nicotinic receptor can have a variant that has been linked to a higher risk of nicotine addiction. But what has especially interested me is how the neuroplasticity of someone’s brain effects these changes. As someone grows up they create and solidify certain connections (or circuits) and lose others. These changes are solidified by environmental factors, meaning that different social factors from childhood (whether bad or good) can either change certain parts of the brain negatively or positively. These factors can lead to a less developed prefrontal cortex (control higher-level cognitive function or decision making), and make someone more at risk for substance use disorder (or addiction).
Excerpt from my notebook (on why adolescents are more at risk for addiction):

Adolescent’s brains are more neuroplastic (neuroplastic- brain’s ability to form new neural connections) than adults and are at a higher risk for negative developmental changes. The prefrontal cortex isn’t finished developing until someone’s twenties, and adolescents make worse decisions based on the lack of higher-level cognitive function. This makes adolescents more impulsive.
A higher level of impulsivity + faster development of the reward pathway (why people take drugs) + limbic-emotional pathways are hyperactive (searching more for rewarding behaviors) = higher risk for substance use disorder

I also have learned about “reward prediction error”. This is connected to how much dopamine is telling you to be excited. Furthermore, as you continue one action that you find rewarding it becomes less and less rewarding the more times you complete that activity. This is how many people end up overdosing because the amount they did the last time wasn’t enough so they take more. Eventually, if you take too much of an inhibitory drug, it inhibits other functions that are important (like breathing). This also connects to why people relapse. When enough time away from that activity happens once someone completes that action again the amount of dopamine that is released (how excited one gets) is higher than previous times. It feels better and so the person partaking in that activity will continue to do so again.

I am enjoying the work I have been doing so far, and can’t wait to continue.

Update on Progress from Weeks 4-6 (include any photos or video if relevant):

Over these last few weeks, I have been continuing to delve deeper into genetics and connect it to my previous knowledge on drugs. We talked about the basics of genetics and DNA. We spoke about how DNA (double helix) codes for RNA (single helix) which in turn codes for proteins (an example of a protein is receptors). A change in DNA can lead to a change in protein which either can have an affect on something or not at all. The reason it may not affect it’s sequence is because there are only 20 unique amino acids (amino acids are the “building blocks” of DNA/RNA), which means that some alteration in the nucleotides (molecules that form DNA/RNA) doesn’t necessarily change the amino acid it creates.

I have been researching how this change in DNA/RNA can affect risk for drug addiction. Specifically I studied the OPRM1 gene polymorphism A118G. The A118G polymorphism is a SNP (single nucleotide polymorphism) of the opioid receptor μ 1. This opioid receptor specifically mediates positive reinforcement to opioids, and is apart of the endogenous opioid system (internal opioids). The job of the endogenous opioid system is to regulate pain, reward, and addictive behaviors. Normal function of the opioid receptor μ 1 is causing pleasure and pain relief when opioids attach. This receptor is also a binding site for exogenous opioids (external opioids) such as heroin or morphine.

The A118G polymorphism replaces the amino acid alanine with glycine at position 118 (which is why it’s identified as A118G). Although there are mixed results, it suggests that this polymorphism increases risk for opioid addiction. The reason that the SNP raises risk is that it has been found to increase binding affinity 3 times. There is some debate on whether or not this is true, but it is widely accepted theory because the A118G polymorphism is more common in Asian and European ancestry. This means there may be potential for generational build up to not make that one polymorphism pertinent. To combat this possibility researchers would like to use a larger test pool. This research can help develop pharmacotherapies to help people struggling with addiction.

In the final few weeks of my honors project, I will gather final information about opioids to connect with my research on the OPRM1 gene. I will then transfer my information into a poster that I can share with the rest of the community.

Update on Progress from Weeks 7-9 (include any photos or video if relevant):

In the final few weeks, I finalized my research by learning about opioid receptors in of itself. I won’t spoil the poster I have also been working on, but we touched upon the 3 opioid receptors (mu, delta, and kappa) and normal opioid function. I thought it was interesting how there wasn’t a lot of research done on the kappa opioid receptor compared to the mu and delta. This most likely has to do with how the kappa receptor isn’t as connected to drug use (compared to mu: main source of analgesic and addiction, and delta: emotions- useful for medication for mood disorders).

It’s also been interesting navigating how to create a scientific poster (I haven’t done one before). I think it’s hard to summarize one’s 9 week long project, but I think I managed to do a good job. I also think it’s nice to have something to look back on and during the process it was nice to recap all that I’ve learned.

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Project by: Farin Weinger (9th Grade)
Project Advisor: Daniel Li
Student(s)’s Advisor(s): Jessica Tan

Description of the Project:

In this honor’s project, I will be learning the basics of neuroscience: anatomy, how neurotransmitters work, and how the brain as an organ works. This project will be over two trimesters: the first (second trimester) consisting of me learning the basics, and the second (third trimester) is where I will delve deeper and learn about the effects of certain types of drugs on the brain.

Final Product (e.g., documents, images, video, audio, poster, display, etc.): N/A (I am continuing into Third Trimester).

Final Reflection on Learning:

Being able to do this honor’s project has been amazing. I have been wanting to delve deeper into biology topics for years, and finally doing this is so satisfying. I feel as if I now understand my chemistry class topics even better just from learning about neuroscience on my own time. Despite doing extra work it has not felt like that, but instead it’s been fun and relaxing at points. Exploring the basics of neuroscience has opened up so many other things I can learn about, for example my continuation of this project into the Third Trimester (Drug Effects on the Central Nervous System).

Overall, this experience has given me so many resources I can use for the rest of my scientific career and I am excited to continue learning more in Trimester Three.

Update on Progress from Weeks 1-3 (include any photos or video if relevant):

The first couple weeks of my honor project has been learning and practicing the basics of the brain and neuroscience as a whole (parts of the brain, neurons, membrane transport, and action potentials). This has been helping me get ahold of what neuroscience means and helping me get used to the type of work I will be doing. I have been reading articles, looking at 3D models, and taking numerous notes. I am also able to have some fun. When I was learning about the Na/K Pump, it is a type of protein channel that helps regulate the flow of sodium and potassium in neurons, we were comparing it to salty bananas. I am glad that I am still able to “goof off” while being productive. 

I will admit that it hasn’t been all salt and bananas, and the content can be quite difficult at times. I am learning above my current science level and that has been difficult. I don’t have all of the background the juniors and seniors in Daniel’s neuroscience class have, but I have kept working on it and believe that I have a good grasp of the content we have covered. I am excited to see what’s next. 

Excerpt from my notebook (relating to membrane transport):

• “Membrane transport: plasma membrane (outside layer of the cell) is a selectively permeable barrier that only lets some molecules in and blocks others
• Types of transport:
• Active transport:
  • • Concentration gradient: low to high
  • Needs energy (ATP) to work
• Passive transport:
  • • Concentration gradient: high to low
  • Doesn’t need energy to work
• Diffusion is the random movement of molecules until equilibrium is reached
  • passive transport = diffusion
• Types of diffusion:
  • Simple diffusion: permeable, transports directly through the membrane
  • Facilitated diffusion: impermeable, needs protein channel/carrier for transport (extra “gate”)
• Cells need active transport when the solutes (a solid/liquid/gas that is dissolved to make a solution) can’t naturally move the way the cell wants it too.
  • Active transport helps regulate what goes in and out.”

Update on Progress from Weeks 4-6 (include any photos or video if relevant):

I have been continuing my learning on action potentials and different types of channels. Action potentials are when a neuron undergoes a series of changes in the membrane potential, this is caused by a change in ion flow. Ion flow changes the potential (charge) of a neuron which then can set off a chain reaction to other neurons. Channels help the flow of ions, and are directly connected to action potentials. There are many different types of channels but the two most relevant to my work are ligand gated channels and voltage gated channels. Ligand gated channels are opened when a ligand attaches (a ligand is like a key). Ligands for the nervous system are neurotransmitters. When the action potential reaches the axon terminal, neurotransmitters are released and will briefly attach to receptors on next neuron that the “message” will get passed too. The neurotransmitter will then come back to the neuron that it belongs too (this process is called reuptake).

Although, it is not easy for an action potential to get properly started. A ligand is used to help reach the “threshold”. For example a threshold could be the change in membrane potential needed to activate the voltage gated channels. Voltage gated channels are opened when a certain change in charge occurs (-55 mV). Sometimes a ligand won’t be able to reach, so to insure that sub threshold stimulus (when the threshold isn’t reached) won’t take place there are different strategies in place. Spacial summation is when a bunch of neurons send a signal to one neuron, so that it will be able to reach the threshold. Temporal summation is when one neuron will send a bunch of signals in a short period of time. This is a great example of problem solving inside of the nervous system.

I have been having a blast learning about topics I have not been able to in my scientific career. It is rewarding to be able to understand these complicated scientific topics and terms, and be able to use concepts in my daily life. I am excited to expand my honor’s project in the Third Trimester.

Update on Progress from Weeks 7-9 (include any photos or video if relevant): N/A Second Trimester was too short for more than 6 weeks.