Neuro Post-it 9: A Deeper Dive into Neuroplasticity
A new series of neuroscientific digestible insights! Written in collaboration with Cesca Centini.
In this edition of Neuro Post-it we’re going to explore more thoroughly the concept of neuroplasticity, including its neurochemical mechanisms and the crucial role it plays in learning, memory, repair and more.
For years, neuroscientists believed that the adult brain is largely static and unchangeable. That we are born with all the neurons we’ll ever have…that neurogenesis only occurs during development…that once we attain maturity our nervous system’s growth will terminate definitely…that those neurons will remain the same size and maintain the same synaptic connections throughout the rest of our life, simply changing the way they interact with each other.
Interesting that this was the general understanding in neuroscience until fairly recently. But pretty much none of that is true, except for the part about the neurogenesis occurring during early development.
So, neuroplasticity. You’ve probably been hearing this term a lot. And no, it doesn’t mean the process of neurons becoming plastic. Simply put, plasticity is the nervous system’s ability to alter its physical structure in response to experience and inputs. It takes place mostly during our early development when our nervous system is still growing and our neurons are establishing connections. But it also continues—albeit not as ferociously—throughout adult life and even elderhood. More and more in-depth research is being done to discover the underlying mechanisms of this fascinating “skill” of the nervous system, with new findings literally getting published every day.
Neuroplasticity is more than just a mechanism for learning and building memories. It plays a vital role in recovering from brain injury, caused by a concussion (for instance), helping re-establish key connections in the brain that have been damaged.
Here’s an analogy to help you understand neuroplasticity better, particularly in the context of restoring brain function after injury: think of neuroplasticity as building a detour around a damaged part of a highway through which cars can no longer pass. These cars represent neural signals, while the highway represents the route through which these signals travel. With this detour, the cars can be rerouted around the damaged section and connect with the rest of the highway, establishing an alternative path around the destruction that allows the cars to flow freely again.
When something like a concussion disrupts the usual flow of information between neurons in the brain, the brain doesn’t just do nothing. It adapts in response and constructs alternative pathways for neural signals to travel, reconnecting disrupted circuits and strengthening synapses to compensate for the diminished activity of the injured areas.
And neuroplasticity isn’t something magical that happens every once in a while in response to major learning experiences or intense brain activity when trying to achieve a task. It’s happening literally every second inside your brain. You reading this text right now and learning new neuroscientific material is igniting plasticity in your brain.
You just don’t know it, until we ask you at the end of the Neuro Post-it series to rehearse everything we talked about and you become surprised at how much you’ve learned along the way. It is directly tinkering with the physical shape of your neural circuits and its connections.
Another thing to keep in mind is that neuroplasticity doesn’t only occur in response to positive learning experiences or to always make you smarter. Repeatedly adopting bad habits is also a basis for plasticity (that’s why it’s difficult to break a bad-habit loop). The more you repeat a bad habit, the more you strengthen the synaptic circuits that make you do it almost automatically. So be mindful, because your brain can also be too adaptable for a lot of wrong reasons.
Building on our last edition about enhancing brain health, we want to place an emphasis on healthy neuroplasticity: adopting good habits, learning for the right reasons, training your brain to become sharper, enhancing your memory, refining your skills, and enriching your thoughts with valuable knowledge and wisdom.
Your brain is hella smart. The fact that it does this on its own without our conscious awareness—and without us having to voluntarily control its activity—is truly impressive. A remarkable and defining feat of the most complex object we know.
Long-term potentiation
The neurochemical mechanism underlying neuroplasticity
Neurons don’t just grow in all directions and latch onto each other to form new synaptic connections. There’s some fascinating and rather complex neurochemistry behind it all. We know chemistry isn’t the most exciting thing to talk about.
so for the sake of Neuro Post-it, we’ll keep it simple and explanatory.
As you know by now (👀), synaptic plasticity is the primary neurological mechanism underlying learning and memory, in addition to being central to the process of brain development.
But what are the fundamental mechanisms that underlie plasticity itself? Where is this plasticity most prominently studied?
When it comes to memory in particular, plasticity is typically measured both in vivo and in vitro in simple circuits found in the trisynaptic pathway of the hippocampus. And this can range from short-term adjustments that last only a few seconds, to changes that last for many years, resulting in long-term memory.
Often, researchers induce and measure changes in synaptic strength through controlled electrical stimulation of this part of the brain. This is the basis for one of the key mechanisms of plasticity, tetanus—a very rapid, energetic burst of electrical stimuli delivered directly to a presynaptic neuron. Tetanus stimulates the presynaptic neuron to generate a series of action potentials in quick succession, flooding the synaptic cleft with neurotransmitters. In response to this bombardment of neurotransmitters, the postsynaptic neuron produces large excitatory postsynaptic potentials (EPSPs).
Over time, the firing of these EPSPs results in a phenomenon called long-term potentiation (LTP), which is a stable and enduring increase in a synapse’s efficiency. This means that these synapses become better at responding to stimuli from an increase in neurotransmitter release, the number of postsynaptic receptors, synaptic size, or by receiving modulatory input from neighbouring neurons.
It’s simple. The more you use a certain neural pathway, the better it becomes at transmitting information. In a sense, you can train your synapses to become more responsive by frequent stimulation.
LTP, on a molecular level, relies heavily on glutamate receptors, specifically AMPA and NMDA receptors.
How does it work?
When a neuron is at rest, its NMDA receptors are occupied by a magnesium ion. When AMPA receptors are strongly stimulated—for instance, during a tetanus—they allow sodium to enter, which depolarizes the membrane and knocks out the magnesium block from the NMDA receptors. Now that the NMDA receptors are open, calcium ions can enter the postsynaptic cell through them.
What’s the point of this influx of calcium ions? They activate a cascade of intracellular enzymes (namely, PKC and CaMKII) that modify a few different aspects of synaptic function:
Movement of existing AMPA receptors to the active synapse
Increased ion conductance at AMPA receptors (making it easier for sodium ions to enter)
Synthesis of new AMPA receptors, enhancing postsynaptic sensitivity
In addition to postsynaptic changes, presynaptic changes also contribute heavily to LTP. The postsynaptic neuron releases retrograde transmitters that travel back across the synapse and trigger glutamate release from the presynaptic neuron. This two-way communication helps further solidify synaptic strength.
The entire LTP process aligns with the concept of Hebbian synapses, which we’ve covered before: neurons that fire together wire together. Again, repeated, successful firing of action potentials strengthens the connection between two neurons over time.
Research, such as this, strongly endorses LTP as an essential molecular mechanism of memory formation. The time course of LTP precisely mirrors that of memory, and experiments like this show that training animals on memory tasks induces LTP in a lot of relevant brain areas.
Neurons will always form new synapses when communication becomes significant enough. This is the key. If one pathway becomes more active than another, it can take over the synaptic sites formerly occupied by the less active pathway. This phenomenon, called competitive synaptic remodeling, ensures that the most frequently used pathways in the brain are preserved and strengthened—shaping and reshaping neural circuits that underlie memory over time. Memory systems are dependent on the ability of the brain to strengthen certain synaptic circuits that involve higher levels of neural activity, while diminishing the strength of others that are used less and are therefore less effective.
While they happen on a micro scale, changes in the wiring of neural circuits by sensory experience and practicing certain motor tasks alters the maps of sensory and motor areas in the cerebral cortex. Examining these brain maps through neuroimaging, we can observe that axonal connections are being physically changed on a large scale as a result of plasticity.
Incredible.
The Man with an “Empty Brain”
a truly powerful case of neuroplasticity
What you’re about to read will blow your mind.
In 2007, The Lancet medical journal reported a case that not just shocked the medical and scientific world, but changed neuroscience as we know it. It was reported that a 44-year-old French government worker walked into a hospital complaining of mild leg weakness—something that, at least at first, doesn’t quite obviously point to problems in the brain. But a few brain scans were taken, and they revealed something unbelievable: his cranial cavity was almost completely filled with cerebrospinal fluid, with just a thin layer of brain tissue surrounding it. In other words, the man was missing the majority of his brain and its key structures. Despite this, he lived a completely ordinary life, which explains why he only found out about his condition after 44 years. He was married, had two children, worked a stable job, and displayed no obvious signs of serious cognitive impairment. His IQ was recorded at 75, which is below average but still within the functional range. In fact, a very high IQ considering how much of his brain was simply absent.
How is this even possible? You guessed it: neuroplasticity.
The unusual condition this person was living with is called chronic hydrocephalus. Breaking down the name, hydro (water) + cephalus (head) refers to water in the cranium, and chronic meaning it’s permanent and becomes progressively worse over time. So what actually happens in this condition? Cerebrospinal fluid gradually accumulates in the brain’s ventricles, which compresses and reshapes the brain over time. Because this buildup happened so gradually—and most likely began in infancy—his brain had decades to adapt to the changing internal environment. What was the consequence of this? It gave his brain the opportunity to reorganize itself in ways that allowed for basic cognitive, sensory, and motor functions to remain intact and functional.
Absurdly fascinating.
This slow onset though was absolutely crucial; had this same condition developed suddenly, it would have likely caused severe cognitive disability or even death. Instead, his brain defied all expectation. Not by resisting the damage, but by adapting around it so well to the point that he never realized most of his brain was nonexistent—until of course he did, still by accident.
This astonishing level of adaptability, that neuroplasticity permits, points to its core mechanisms. One such mechanism is functional reorganization, in which brain tissue that survives damage takes over the roles of damaged or missing regions that are no longer functional. The brain also relies heavily on distributed processing, meaning that functions such as memory formation, the processing of language, and decision-making are not confined to just one region but are shared across networks that consist of multiple neural circuits. This redundancy allows for the compensation of lost neural function, and is how this individual’s brain was able to function despite 90% of it not being there.
Stories like this make you appreciate just how unfathomably capable our brains—and ultimately our neurons—truly are.
Looking ahead
By the time the nervous system—and particularly the CNS—has attained full maturity by around our mid-20s, it is stable and adept at navigating many of life’s problems. But as we age, the ability of our nerve cells to adjust their conformity and connections in response to the environment and personal experience deteriorates. As a result, our nervous system declines in its ability to repair itself from disease or injury and our ability to learn new skills or knowledge becomes more difficult, demanding a lot more effort. For this reason it’s recommended that we learn as many new skills as we can while we’re still young—such as learning a new language—as we’re able learn a lot more efficiently thanks to much higher rates of neuroplasticity.
As we learned in our last edition of Neuro Post-it, though, there are many ways to delay this neurological aging and keep our brains active with consistent exercise, learning, and of course proper nutrition and rest to ensure healthy brain function. And with new technological innovations, neuroscientists are already breaking frontiers in restoring “young plasticity” in older individuals.
The neurons in the developing CNS (which encompasses the brain and spinal cord) are incredible. Why? Because of their extraordinary ability to grow their axons to the correct targets, changing their shape and synapses adeptly in response to environmental influences. Now imagine if we could revert neurons of the mature CNS to this early developmental state and restore their ability to grow and form new synapses with other neurons. With this power in our hands, we can potentially repair damage from traumatic brain injuries or even reverse the effects of devastating neurodegenerative diseases, saving millions of lives globally every year.
The future of neuroscience is truly exciting, and much of it lies in the tremendous capacity and potential of neuroplasticity.
Resources and interesting bits:
Whitlock, J. R., Heynen, A. J., Shuler, M. G., & Bear, M. F. (2006). Learning induces long-term potentiation in the hippocampus. Science (New York, N.Y.), 313(5790), 1093–1097. https://doi.org/10.1126/science.1128134
Graham L. Collingridge, Long-term potentiation in the hippocampus: From magnesium to memory, Neuroscience, 2024, ISSN 0306-4522, https://doi.org/10.1016/j.neuroscience.2024.11.069.
Caya-Bissonnette, Léa et al. Current Biology, Volume 34, Issue 13, R640 - R662
Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003
TEDx TalksImproving our neuroplasticity | Dr. Kelly Lambert | TEDxBerm…
Feuillet, L., Dufour, H., & Pelletier, J. (2007). Brain of a white-collar worker. Lancet (London, England), 370(9583), 262. https://doi.org/10.1016/S0140-6736(07)61127-1
https://www.sciencedirect.com/topics/neuroscience/long-term-potentiation
As always, co-written beautifully with my partner in crime,
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