How do people actually study neuroscience & pharmacology?

[HappyHedgehog]

Forgive me if this sounds like a stupid question, but how do you actually study neuroscience & pharmacology without just reading what other people have found?

What I mean to say is how to actually advance scientific knowledge and discover something new?

What technology or methods are used to study the brain, central nervous system, drug interactions, etc? Can an individual get ahold of this equipment or do you need a lot of money and lab?

Like I've read a lot about dopamine, serotonin, drugs causing various effects like changes in heart rate or muscular strength, but how the hell is this stuff actually measured and studied?

How do you see dopamine actually moving through the brain and neuroreceptors working? How do you see brain damage or brain improvement? How do you test muscular strength and response times? How do you measure conciousness and the changes of it?

Again I apoligize for the difficulty and expressing this. Basically I want to not only expand my knowledge as an individual, but perhaps expand mankind's collective knowledge and perhaps even find something new before discovered. How are these discoveries made anyway?

 

[serotonin2A]

The easiest way to satisfy your curiosity about how studies are performed is to find a few pertinent papers and read over their methods sections. For detailed descriptions of the experimental protocols used in neuroscience, you can take a look at the following:

http://onlinelibrary.wiley.com/book/10.1002/0471142301/homepage/archive.htm

You need a lab and substantial resources in order to perform neuroscience research that will advance scientific knowledge. The days of doing inexpensive neuroscience experiments at home have long since passed. Any work done in humans or animals needs to be reviewed and overseen by a variety of ethics/safety committees.

 

[IamaBonobo]

You conduct experiments. That's what most of those scientific papers are- people writing up the results of an experiment. Any neuroscience or pharmacology study definitely needs a full lab with funding. These experiments can be extremely expensive. Some of my studies can run up to about $5-6k for a cohort of animals, and a typical publication requires about 3-4 cohorts so you can see how critical it is to be supported to conduct this kind of research.

 

[Cotcha Yankinov]

I would look up for example a radioligand binding assay for figuring out a drug's affinity at a particular receptor.

 

[adder]

perhaps expand mankind's collective knowledge and perhaps even find something new before discovered. How are these discoveries made anyway?

That's the goal of most scientists, albeit for very different reasons I imagine. New discoveries aren't made every day, most scientific papers that are published are extensions of what is already known, in order to come up with something completely new, apart from being well informed in your discipline you do need to have an ability to look beyond the system in which everything is described at the moment. Unfortunately, I doubt it can be achieved outside of academia (well, unless you're a wealthy man and have great resources to conduct research by yourself) and it is governed by its rules too so it's not that easy to start trying out your own ideas right after getting a diploma (unless you're really really lucky). On the other hand not all fields of science let you work effectively all by yourself.

 

[Nagelfar]

To the OP, for a short explanation of one question you laid out; how are neurotransmitters like dopamine watched as they move through the brain: this is a process known as radio-ligand creation. For dopamine (includ. serotonin & NE) it is usually [³H]dopamine which is dopamine made with tritium, which is one step "heavier" than 'heavy hydrogen'; this is instead of basic hydrogen (i.e. [¹]H) which can be viewed with scanning equipment because it diverges from the ubiquitous presence of 1-hydrogen in the body and nearly all molecules; it's presence is unnatural and has a more "condensed" presence, one could say, and it works basically the same as hydrogen. It does skew the binding profile a small measure, but this then almost becomes an issue of the measurement paradox (but in the domain of molecular science and not atomic, rather because it has to be altered to stand out from other molecules)

This is also done in dissected tissue, where it is 'washed out' with buffer and observed up close with various methods and tools.

As for checking the efficacy of a ligand to a transporter, e.g. the dopamine transporter or serotonin, they replace hydrogen with tritium on a ligand already known to bind, and they see to what degree the new ligand displaces this litmus-standard ligand and further to what degree the ligand is able to inhibit the re-uptake of the neurotransmitter of the transporter in question.

If anyone can clarify anything faultily explained in the above I'd be happy for any correction. Any further question on the above I'd be happy to clarify to the degree I am able.

 

[serotonin2A]

To the OP, for a short explanation of one question you laid out; how are neurotransmitters like dopamine watched as they move through the brain: this is a process known as radio-ligand creation. For dopamine (includ. serotonin & NE) it is usually [³H]dopamine which is dopamine made with tritium, which is one step "heavier" than 'heavy hydrogen'; this is instead of basic hydrogen (i.e. [¹]H) which can be viewed with scanning equipment because it diverges from the ubiquitous presence of 1-hydrogen in the body and nearly all molecules; it's presence is unnatural and has a more "condensed" presence, one could say, and it works basically the same as hydrogen. It does skew the binding profile a small measure, but this then almost becomes an issue of the measurement paradox (but in the domain of molecular science and not atomic, rather because it has to be altered to stand out from other molecules)

This is also done in dissected tissue, where it is 'washed out' with buffer and observed up close with various methods and tools.

As for checking the efficacy of a ligand to a transporter, e.g. the dopamine transporter or serotonin, they replace hydrogen with tritium on a ligand already known to bind, and they see to what degree the new ligand displaces this litmus-standard ligand and further to what degree the ligand is able to inhibit the re-uptake of the neurotransmitter of the transporter in question.

If anyone can clarify anything faultily explained in the above I'd be happy for any correction. Any further question on the above I'd be happy to clarify to the degree I am able.

Just to clarify, in terms of binding, tritium works exactly like protium ([¹H]). As Nagelfar stated, radiolabeled dopamine can be used to visualize dopaminergic projections. However, modern studies wouldn't use [³H]dopamine but rather a radiolabeled dopamine precursor that undergoes beta decay, such as [¹⁸F]DOPA. Once in the body, [¹⁸F]DOPA is metabolized to [¹⁸F]dopamine, which can be detected by PET scanning.

There are, of course, other methods that are more widely used to detect dopamine in the brain. Extracellular dopamine levels can be quantified by analytical means, such as microdialysis, voltametry, or dopamine-selective electrodes. ELISA can be used to quantify the total level of dopamine in a particular brain region. The location of dopamine can be visualized using dopamine-specific antibodies (via immunohistochemistry).

 

[HappyHedgehog]

Thanks to all responses!

 

[Nagelfar]

Just to clarify, in terms of binding, tritium works exactly like protium ([¹H]).

I thought there were small, molecular weight, etc., changes that are very minūte in scale but detectable; i.e. "dopamine" diverges in a minuscule, if not infinitesimal (statistically unimportant but certainly existing), reuptake assay from [³H]dopamine; in terms of hydrogen binding and all the functional methodologies otherwise yes, but am I correct in my qualification of it not so being 'exactly' when it comes to binding that becomes so affected as by things like quantum electron cloud shape, etc. I am almost certain I read that there is a shift in values when compounds are labeled in such ways; there is even a shift in values between protonated and freebase of the same compound at their shared target site; though, again, very minor.

 

[serotonin2A]

I thought there were small, molecular weight, etc., changes that are very minūte in scale but detectable; i.e. "dopamine" diverges in a minuscule, if not infinitesimal (statistically unimportant but certainly existing), reuptake assay from [³H]dopamine; in terms of hydrogen binding and all the functional methodologies otherwise yes, but am I correct in my qualification of it not so being 'exactly' when it comes to binding that becomes so affected as by things like quantum electron cloud shape, etc. I am almost certain I read that there is a shift in values when compounds are labeled in such ways; there is even a shift in values between protonated and freebase of the same compound at their shared target site; though, again, very minor.

It is true that in certain situations radiolabeling can result in altered affinity, for example when a non-iodinated ligand is radiolabeled with iodine. But the affinity difference occurs because the unlabeled and labeled ligands are different chemicals.

Adding one or two neutrons doesn't change any of the electronic or steric properties that are involved in binding. The extra mass can slow chemical reactions, but that isn't relevant to reversible binding.

EDIT: Here is a study that is relevant:

http://www.ncbi.nlm.nih.gov/pubmed/25901328

 

[TheBlackPirate]

Simple neuroscience research is 100% accessible. Anybody could be involved with neurosience if they are willing.

Research the scientific method. Create a hypothesis, test your hypothesis, analyze your results, and make conclusions on your research project.

Here's a good project. Anecdotal evidence suggests the legal tryptamine melatonin induces lucid dreams, especially when combined with a dream journal.

Hypothesis: If I consume 1mg of melatonin every night before I sleep and journal my memories of dreams in the AM, then the intensity and frequency of my lucid dreams should increase during this cycle.

Go ahead, have a dream, journal.