The Neurotransmitter Showdown: GABA v Glutamate in the Courtroom.

The Neurotransmitter Showdown: GABA v Glutamate in the Courtroom.

GABA: Good day, Glutamate. How do you plead today?

Glutamate: Not guilty Your Honor. My actions were justified.

GABA: Oh, please. You know that you always overexcite the receptors and cause chaos in the brain.

Glutamate: That's simply untrue. I only activate the NMDA, AMPA, and kainate receptors as needed.

GABA: Needed? 

Your excessive activation of those receptors leads to seizures and neurotoxicity and not to mention hyperactivity, mood swings, social communication challenges, and sensory dysfunction in autistics. 

You are totally implicated in the Excitatory-Inhibition Imbalance theory in autism.

Hari: You Said It, GABA!! Tell it like it is. 

Judge (pounding table with mallet): Order in the court! The audience is not allowed to speak. 

Hari: Your Honor, I was not speaking out loud. It was all in my mind. 

Judge: But we are in your mind so everyone here can hear you. 

Hari: Oh, Ok. Then I'll go off and take a nap. 

Judge. Thank you Hari. 

(Pounding with mallet) Order! Order!I call order in the courtroom!

Glutamate: Now, now, GABA, let's not exaggerate.

You know as well as I do that I'm not solely responsible for seizures and everything autism.

And, hey, I can't help it if the receptors are just so darn receptive.

What about you, GABA? Always inhibiting with the GABA-A and GABA-B receptors. Can't you let loose a little?

GABA: More like attempting to rein in your recklessness.

Glutamate: Fine, but don't act like you're the only one with inhibitory powers. 

I have the mGluR and NMDA receptors to help balance things out.

GABA: Ha, those receptors are no match for the power of the GABA receptors, who are the real heroes here, preventing excess neuronal activity and maintaining balance in the brain.

Glutamate: (chuckles) You inhibitory types always take things too seriously. 

Without my glutamatergic transmission, the brain would be in a constant state of inhibition. 

Can you imagine a world where nothing ever happens?

GABA: Can you imagine a world where everything is chaos and nothing is under control? 

That's what you bring to the table, Mr. Glutamate.

Glutamate: Hey, you make it seem like I'm the bad guy.

NMDA-Receptor (Junior Lawyer): That's right, GABA. Glutamate and I won't stand for this injustice. How do you plead to the counter-charges laid against you for excessive inhibition of the brain?

AMPA-R (Junior Lawyer): (sighs) This is going to be a long trial.

GABA: Objection, Your Honor! My esteemed colleagues are making baseless accusations without any evidence to support them.

Glutamate: Oh please, GABA. Your main job seems to be to inhibit my signals.

GABA: Yes, that may be true, but I do so within the confines of the law. 

I bind to GABA-A receptors and activate chloride channels, which hyperpolarizes the cell and reduces the chance of action potentials firing.

Glutamate: And yet, you can't deny that you're involved in a lot of shady activity. 

You're implicated in seizures, anxiety, and even addiction.

Admit it, GABA, you're a downer!

GABA: I resent that label, Glutamate. 

I may be inhibitory, but I provide balance and prevent excess excitation.

And let's not forget that you, too, have a dark side. 

Your overactivity is implicated in a host of disabilities, from epilepsy to Alzheimer's.

Glutamate: Ah, but that's only because I'm so versatile. 

I not just bind to a variety of receptors, but mediate many different functions. 

I'm the jack-of-all-trades neurotransmitter.

GABA: And yet, you can't deny that your actions have consequences. 

Too much glutamate can be toxic and lead to neuronal death. 

You need me to keep you in check.

Glutamate: (smirks) Oh, GABA, you never cease to amaze me with your sense of humor

GABA: (sighs) Fine, but don't think you're off the hook just yet, Glutamate

Glutamate: Hmph! I suppose we'll just have to agree to disagree.

Judge: (Pounding mallet)

Order in the court! Both neurotransmitters have made their case. 

The jury will now deliberate and reach a verdict on the relative contributions of Glutamate and GABA to brain function.

Bailiff! - Please escort jurors Acetylcholine, Dopamine, Norepinephrine, Serotonin, Histamine, Adenosine, Nitric oxide, Substance P, Endorphins, Anandamide, Neuropeptide Y and Orexin to the Jury Deliberation Room. 

Since this is a high stakes case, I declare that that the jury be sequestered. You have to make a decision before Hari wakes up. 

(Pounding Mallet) 

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PART 2. 

Jury Proceedings of the 12 member jurors - Oh the Drama!!

Inside the Jury Deliberation Room 

Dopamine: Sequestered? Finally, some peace and quiet away from the hustle and bustle of the synapse.

Acetylcholine: Sequestered sounds like a right proper holiday to me!

Oxerin: Yeah, you would say that, mate. 

Always looking for the next thrill, you are. 

Maybe we should sequester you two permanently!

Histamine: What are you talking about? 

I can't stand being cooped up for too long. 

I need to be out there regulating inflammation and allergic reactions.

Serotonin: I agree with Histamine. 

I need to be out there regulating mood and social behavior. 

Being cooped up for too long can make me go crazy.

Norepinephrine: Hey now, let's not get hostile. 

We're all here to do a job. 

Can we focus on the case, please? 

Adenosine: I don't see what the fuss is about. 

Sequestered or not, my job is to regulate sleep and wakefulness. 

It's all the same to me. 

Oxerin: But we are on a timeline. Sequestered or not, we need to wrap up before Hari wakes up. 

And definitely before I get the  REM going, else we are going to have random vivid dreams wandering in here and interrupting our discussion.

AcH: Ha! Fat chance of that happening Oxerin. 

During REM, I rise to the occasion and paralyze the muscles so that dreamers don't engage walk abouts. 

Neuropeptide Y: I'm just happy to be here, folks. 

Let's get down to business and deliberate like the impartial jury we are.

Anandamide: I concur! 

As the calmest and most rational among us, I suggest we focus on selecting a foreman first then get the the task at hand. 

I nominate myself.

Dopamine: Ha! I knew you'd pick yourself, Anandamide. 

You were always one for self-promotion.

Anandamide: That's not true, Dopamine. 

I simply thought I was the best candidate for the job.

Norepinephrine: No way, I should be the foreman. 

I have more experience in making tough decisions.

Dopamine: I should be the foreman, I'm the most intelligent one here!

Histamine: You're all wrong, I should be the foreman. 

I'm the most level-headed of all of us.

Serotonin: I agree that Histamine would make a great foreman.

Acetylcholine: What about me? 

I'm the neurotransmitter associated with learning and memory. 

I think I would make a great foreman!

Neuropeptide Y: Oh, come on. 

Can't we just pick someone already? 

I have places to be!

Anandamide: Hey, everyone, calm down. 

My name means 'bliss molecule'. 

I think that makes me the best candidate one here.

Endorphins: I like that. Anandamide. 

I'm feeling pretty good about a blissful decision.

Substance P: Yeah, I'm good with that too.

Nitric Oxide: Me too. Let's get on with it already.

Adenosine: Agreed. Let's just make a decision and get out of here.

Dopamine: Fine, whatever. Anandamide can be the foreman. 

Let's just hurry up and make a decision.

Norepinephrine: I agree. Let's get this over with.

Anandamide: I call this jury to order. 

 We need to determine the relative merits of glutamate and gaba as excitatory and inhibitory neurotransmitters.

Histamine: I agree, but let's not forget about the role the rest of us play in this. 

Some of us are excitatory and some of us are inhibitory too.

Adenosine: And some of us are both, depending on the circumstances.

Nitric oxide: Exactly. 

It's not as simple as just saying one neurotransmitter is too excitatory or too inhibitory. 

It all depends on the context."

Substance P: Well, I think we can all agree that glutamate does have a tendency to get a bit carried away sometimes. 

Oxerin: Glutamate is clearly too excitatory. We need to rein it in.

Serotonin: I don't know, I think glutamate has its place. 

It's important for learning and memory, for example.

Histamine: Yeah, but too much of it can cause all kinds of problems. 

I've seen it firsthand

Endorphins: But let's not forget that GABA can be a bit of a wet blanket too. 

It's so inhibitory, it practically puts you to sleep

Nitric oxide: That's a bit unfair. GABA is important for regulating anxiety and stress.

Substance P: But it can also make you feel numb and disconnected from your emotions.

Dopamine: Hey, let's not forget about the good things GABA does, like reducing pain and promoting relaxation.

Anandamide: I agree. 

And glutamate isn't all bad either. 

It's involved in so many processes, from sensory perception to motor control.

Anandamide: I think we need to be objective here. 

We can't let our own biases cloud our judgement.

Neuropeptide Y: Yes It's a tough call, but I think we need to weigh the pros and cons carefully.

Nitric oxide: Exactly. It's not as simple as just saying one neurotransmitter is too excitatory or too inhibitory. 

It all depends on the context.

(After much discussion ...... the jury is unable to reach a verdict.)

Anandamide: I think we've heard enough. 

It's clear that there are valid points on both sides. 

I propose that we declare a hung jury.

Dopamine: What?! 

We can't do that! 

We have a responsibility to come to a conclusion!

Acetylcholine: I agree with Anandamide. 

Sometimes it's better to admit that we don't have all the answers than to rush to a decision.

Histamine: I suppose that's true. 

Let's inform the judge of our decision.

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Coming soon. Does the Hung Jury lead to a re-trial with new witnesses and more drama?