For a long time, neuroscientific dogma dictated that the brain is hardwired. This was cemented by the venerable father of cellular neuroscience, Ramon y Cajal, when he said: “Nerve paths are something fixed, ended, immutable. Everything may die; nothing may be regenerated.” That means no repair, and no rearrangement. (Although aparrently his opinions on this were somewhat ambiguous.) However, its pretty apparent that our minds change over time – every day, likely every second – so if our brain is the seat of the mind, shouldn’t our brain also change? It was well known that neurons in the peripheral nervous system could regenerate, but the dogma of the immutable brain held for the central nervous system. Then, in the 1980’s, Albert Aguayo’s lab at McGill discovered that, when given the appropriate environment, neurons in the brain retain the ability to regenerate and in so doing they opened a whole new field of study. We have yet to see major benefits of the study of central neural regeneration, but then again we have yet to understand the related natural processes that actually keep it from happening. While things are steadily chugging along in the study of regeneration, there is a whole other field looking at the normal, day to day changes in our brain. The ability of our brains to change is referred to as neural plasticity. (Think malleable plastic.) In fact, the brain can change on a grand scale. For instance, when you lose a finger, the area of the brain that used to control that finger can be recruited to help control the remaining fingers with better accuracy. Although if you are a struggling instrumentalist I wouldn’t recommend cutting off your pinky. (Unless you play with your feet – my father convinced me when I was young and impressionable that the pinky toe is thoroughly useless and would be lost to evolution in a matter of generations.) While large swathes of neurons can change their function, neural plasticity is also thought to be the basis of memory formation. But regardless of the result of neural plasticity on the level of behaviour and the mind, it involves physical change on the level of neuronal networks, cells and synapses. Synaptic plasticity in particular has been studied in extreme depth, albeit with a lot left to learn. At its most basic level, synaptic plasticity can involve appearance of new synapses, disappearance of preexisting synapses, and strengthening or weakening of synapses. The basic idea is that memory formation involves strengthening and/or formation of new synaspes, while memory loss involves the opposite (or just straight up cell death), but it is almost certainly more complex than that.
So, although Ramon might roll in his grave, I will say very firmly that the brain is not hard wired. Change is possible.
To this effect, a study just published in Nature Neuroscience by Chen and friends looked at the plasticity of inhibitory neurons in the visual cortex, one of the first brain regions where plasticity was studied. David Hubel and Torsten Wiesel, who I’ve written about briefly in the past (point #3) discovered a lot about the mammalian visual system, and laid the groundwork for a lot subsequent experimenting done on visual plasticity.
Their first major discovery was their identification of Orientation Selectivity of neurons in the visual cortex. Orientation selectivity refers to the ability of a single cell to respond specifically to a bar of a certain orientation presented in a specific location in the visual field. To be clear, orientation selective neurons are located in the visual cortex at the back of the brain, and become active when the eye see’s a bar of particular orientation (these neurons receive input from the neurons in the eye). You can read more about visual stimulus selectivity and how it arises in a couple of my recent posts.
Their next major discovery was that neurons in the visual cortex are arranged in columns that run perpendicularly into the brain, starting at the outer surface and extending up to ½ a centimetre inward. The main thing to know about these columns is that each one mainly receives input from either the right or left eye. Thus the columns are referred to as Ocular Dominance Columns, since either the left or right eye dominates the input into each column.
Hubel and Weisel’s third major discovery is where they broke into the world of neural plasticity. In particular they identified experience dependent plasticity of ocular dominance columns. They found that when they raised kittens with one eye stitched shut, a procedure termed monocular deprivation, there was an ocular dominance shift that resulted in the non-deprived eye being more heavily represented in the visual cortex, with columns receiving input from the non-deprived eye that were physcialy much bigger and contained more cells than the columns receiving input from the deprived eye. So the overarching idea is that, if you alter the experience of developing circuitry (ie by closing one eye), you change how that circuitry develops. Another major finding by Hubel and Wiesel was that there is a critical period of time in which this experience dependent plasticity can occur. Since that point critical periods have been identified for lots of other developing systems, the most notable being language acquisition; after a certain age it is much more difficult to a acquire a new language.
Their discovery of a critical period for experience dependent plasticity indicated that the adult brain is less plastic than the developing juvenile brain and that you don’t expect to see ocular dominance shifts when an adult undergoes monocular deprivation. However! Hubel and Wiesel were working in the cat, and it turns out that rodents seem to retain a unique propensity for experience dependent plasticity into adulthood, showing ocular dominance shifts following monocular deprivation at mature ages. (If you are skeptical, here is a good paper.) This makes the rodent visual system an ideal model for experience dependent plasticity of cortical circuitry in adults.
So, making use of this unique feature of the adult mouse visual system, the Nedivi lab (home of Chen and friends) has been looking at plasticity of inhibitory interneurons in the visual cortex since the early 2000’s. To remind you, dendrites are the information gathering arms of neurons, onto which synapses are made. So, you can imagine that changing the structure of dendrites, making them shorter or longer, thus taking away or adding synases, could be a form of plasticity. It turns out that the folks in the Nedivi lab are pretty sure they found the first unambiguous evidence of dendritic remodelling involved in neural plasticity. In a 2006 paper they found that the tips of dendritic branches of inhibitory interneurons in the mouse visual cortex elongated and retracted “on a day to day basis.” Then, in their next paper they showed that there is a specific “dynamic zone” (corresponding to a superficial layer of the visual cortex) where interneuron dendritic branch tips are more plastic than those of other adult neurons. In their most recent paper, which I review in depth here, Chen and friends show that the ambient levels of plasticity they see in these neurons is tripled following monocular deprivation similar to that done by Hubel and Wiesel in the ’70’s. The message they are sending here is that this population of superficial inhibitory neurons that retains a high level of plasticity into adulthood is a kind of master mediator of cortical neuroplasticity. It would be extremely interesting to see if the same things occur in other areas of the cortex known to be plastic into adulthood – for instance in the finger region of the motor cortex following loss of a finger. This body of work could be laying new groundwork for studying structural plasticity in other brain regions, which I find really exciting.
Something even more tantalizing, though, is the tidbit that Chen and friends leave off with. Fluoxetine, better known as the extremely popular antidepressant, Prozac, restores the visual cortex to a “juvenile” level of plasticity. So Chen and friends tested it on their mice to see how it affected the dynamics of the dendrites they were looking at. They found that when they combined the fluoxetine with monocular deprivation, the structural plasticity of the dynamic zone inhibitory neurons is even greater! From this they make the tentative conclusion that combining fluoxetine treatment with some kind of “instructive stimulus” may enhance experience dependent plasticity of circuitry, allowing for better recovery from depression, obsessive compulsive disorder, and other mental illness that may require some kind of neural rewiring. To me this evidence is extremely promising since that instructive stimulus could be something like cognitive behavioral- or talk therapy. Combining fluoxetine with something like that won’t require long-winded clinical trials; people can just start doing it, although I would imagine this has begun already.
Although I’ve said it about many other papers, I can’t help myself here: All told, unless you want to deprive yourself, this is one more group to keep an eye on.