Your Brain on Thirsty Thursday
Happy Thursday! Thursday, glorious Thursday. During my college days, Thursday was indisputably the greatest day of the week. It was the long-awaited start of the weekend, that relished moment when we slipped across that magic line between Work Hard and Play Hard. Out came the Burnett’s handles and the shot glasses, on went the heels, up went the volume on the pregame playlist, and away flew the stresses of the week.
Fast forward about five hours to last call. Leaning on your best friend as those heels got wobbly. Channeling the liquid courage to make seductive eye contact with that night’s crush. Drunk tears, drunk fights. Or my personal favorite, the spontaneous DFMO. Fast forward another few hours to the hungover dining hall recap: clinging to coffee or some horribly neon sports drink, seeking out any form of greasy carbs, piecing together the night from the fragments of everyone’s memories. Oh Thursday, always a terrible beauty.
Alcohol: loss of motor coordination, a sense of invincibility, amplified emotions, loss of inhibition, hazy memory, blackout. What kind of crazy things are happening in the brain?! How does alcohol even get into the brain?!
Usually, toxic molecules in the bloodstream cannot enter the pristine brain tissue. The blood vessels in the brain possess a series of unique qualities (compared to blood vessels in other organs) that allow them to vigilantly regulate what moves between the blood and brain tissue in either direction. This is called the “blood-brain barrier”. But ethanol (the active ingredient in alcoholic drinks) is a sneaky little betch with molecular properties that allow it to slip past the barrier with relative ease and seep into the brain tissue, where it changes activity patterns all over the brain. This is the reason that drinking causes so many varying symptoms—ethanol affects human behavior in a different way for each brain region it acts upon.
Gaga GABA, breaking the Poker Face & increasing chances of Bad Romance
Many of the effects of acute exposure to ethanol involve a particular molecule called gamma-Aminobutyric acid, fondly known as GABA. To understand what GABA does and why messing with it wreaks havoc, it is important to grasp the basics of neural transmission. Each brain cell has an incredible number of little channels in its cell membrane, and each channel can be opened or blocked by molecules with a particular shape. When the channels are open, they allow specific ions—molecules with a positive or negative charge—to flow into or out of the cell. Once enough positively charged ions enter the cell (reaching a specific “threshold” charge), all hell breaks loose. There is an incredible influx of ions, lots of intracellular changes, and an electric current flows through the cell—the cell “fires” an “action potential.” [To learn more about action potentials, check out this video by NeuWriteSD’s own Alie Astrocyte!]
Where does GABA come into play? The particular cell membrane channels that GABA binds to (“GABA receptors”), allow negative ions to flow into the cell when GABA binds and activates them. These negative ions bring the cell further from that sweet spot of action potential threshold—they make it harder for the cell to fire. This is referred to as neural “inhibition.”
Ethanol can mimic GABA, binding GABA receptors on the surface of neurons and making those neurons less likely to fire. Depending on the brain region in which this is happening, this increased inhibition can have different effects on behavior.
For example, neurons in the prefrontal cortex are important for preventing impulsive, socially inappropriate behavior. Decrease their ability to fire, and suddenly you’re drunk texting your ex. The prefrontal cortex is also responsible for judgment and decision-making. Remove the brakes of the prefrontal cortex and you’ve decided you should invite your DFMO partner home with you.
The cerebellum is essential for making coordinated movements. An incredible wealth of sensory information including the current whereabouts of your limbs is routed to the cerebellum, where it is intricately integrated and passed forward to the areas of your brain that influence motor planning and activity. Not only can ethanol mimic GABA and inhibit this coding process, but scientists have shown that, in the cerebellum, ethanol can also act on the cells that are sending the normal GABA signal, causing them to release more of it. As the cerebellum loses its ability to integrate sensory information, your reaction time slows and you start stumbling about. Hopefully your questionable DFMO partner can at least provide some structural support and prevent a dance floor wipe out (DFWO?).
I live for the nights I can’t remember // With the people that I won’t forget
The science behind the phenomenon of blacking out is not related to ethanol’s action at GABA receptors. Ethanol also happens to act on another neuronal membrane channel: NMDA receptors. In contrast to GABA receptors (which are channels for negatively charged ions), NMDA receptors let a couple types of positively charged ions into the cell. NMDA receptors play an irreplaceable role in synaptic plasticity—the ability to change the strength of the connection between two cells. A simplified explanation: if Neuron A talks to Neuron B a lot, Neuron B eventually becomes more sensitive to signals from Neuron A. Not unlike two friends growing closer over time. This phenomenon is called long-term potentiation or “LTP” and without NMDA receptors and their downstream signaling, LTP doesn’t happen.
LTP in the hippocampus is thought to underlie memory formation. Particular sets of neurons that get activated by a scene in the outside world are strengthened as a unit, and this unit—a clique of neurons to continue with the friendship analogy—is the physical substrate of the memory. If one of these cells is activated, the rest are more likely to be activated as well, and the precise combination of them replays the original event in your mind. This concept is still somewhat hypothetical but is gaining ground in the field. [For more on this, check out Dan’s post on Inception.] Alcohol has been shown to block NMDA channels, thereby temporarily preventing LTP and the formation of new memories. This is why you may have trouble remembering the facial features of your DFMO friend the next morning.
Gimme gimme more // Gimme more // Gimme gimme more
While releasing your inhibitions might feel freeing once in a while, the effects of long-term alcohol abuse are rather… sobering. In addition to its myriad other effects, ethanol activates your brain’s pleasure and reward centers, which can lead to addiction. In cases of chronic alcohol abuse, many of the issues discussed previously (for example, motor coordination and memory formation) can become permanent problems.
Cheers to the frickin’ weekend! #champagneformyrealfriends
As it’s Thursday and drinking plans might be imminent, I won’t leave you with images of decrepit brains shrunk by serious alcoholism. A better take-away message is that your brain is continuously operating in an incredibly complex balancing act between excitation and inhibition, the mechanisms of which are similar throughout the brain, despite the very different roles of each brain region in determining behavior. Interrupt this precious, fragile balance, and you can cause a quite noticeable change in behavior and mental state. While drinking to the point of disrupting memory formation is not advised, a splash of liquid courage or disinhibiting your dance move prowess might just be the recipe for making tonight a great one.
- Bar: Temple Bar by Larry Koester (https://www.flickr.com/photos/larrywkoester/15639078315/in/photolist-pPYn8i-adLWHS-6RoWQK-puHCCQ-eaLoYh-594gQB-5eZJoi-7k9E6k-aLnx6Z-P6RMD-6PPVBo-5VNSsH-4KD6Dh-pr2cbw-861Qcs-aUXRRK-9U4jny-6N7Kiv-eaLmrq-6dZhfx-9oecWo-69BuSy-e7WLuu-4dHCPw-DoHhX-a4XJEW-qjS4go-adJ4Wp-8WquCJ-5CamyB-FUrGt-N8mFo-efaf3-eaELx6-deMs9B-eaLq5W-r8yjH-6ZYz4Q-BmFS9E-b8jNkD-eaEKRx-eaLp7G-4n8PMs-5P1ACt-qdZB2Z-4Wy1k8-9oqjW2-5HX7aa-aUXScx-4zbK6i)
- Synapse diagram – https://en.wikipedia.org/wiki/Reuptake
- Champagne – Bill Mason, MCU035 (https://www.flickr.com/photos/maxblogbits/3324879428)