Plastic axonal trees

You can’t teach an old dog new tricks…or can you?

We’ve all heard about how the brain slows down as we age.  We’re constantly losing brain cells.  Neurons become “static” and cannot make new connections.  Is this true?  Are we really doomed to a lifetime of deteriorating mental function?

A paper by Oberlaender et al came out this week in the journal Neuron that disputes this common view of the adult brain.  They studied plasticity in the adult rat somatosensory cortex.  Plasticity refers to the ability of neurons to change shape, connections and activity levels in response to environmental changes.  The somatosensory cortex is the area of the brain that processes touch sensation.  In the rat (and mouse), the somatosensory cortex is organized into barrels, where each cylindrical chunk of brain responds only to signals sent from an individual whisker.  The sensory nerves in a whisker travel to the brainstem first, then they make a stop in the thalamus (a deep region of the brain), and finally the thalamic neurons synapse with cortical neurons in layer 4 (remember that the brain cortex is arranged into 6 layers). 

The somatosensory circuitry, from a sensory neuron (pink) 
to the brainstem (medulla) to the thalamus and then somatosensory cortex.

It has been shown before in the adult rat somatosensory cortex that the neurons can undergo structural and functional changes in response to changes in activity.  This kind of plasticity has only been observed before in the cortex; other areas of the brain were thought to be static once the brain reaches the adult stage.  Oberlaender et al. show, however, that the neurons from the thalamus can also undergo structural changes in the adult brain.

Changes in axonal morphology

To induce neuronal plasticity, the researchers trimmed a single whisker on a group of rats.  This is a painless procedure, so they don’t have to take into account responses due to an injury.  This trimmed whisker will no longer be sensing the environment, so its sensory neurons will be silent.  Three days later they filled the thalamic neurons associated with that whisker with a dye, so they could image the shape of the neurons. 

We need to take a brief pause here to discuss neuronal anatomy: Neurons have a round cell body, dendrites which receive signals from other neurons and axons which send signals to other cells.  Axons can travel great distances and make synapses with many different cells.  The general consensus in the field is that as we learn something new, more synapses and connections are made between neurons.  The image below is a thalamocortical rat neuron (a thalamic cell that makes synapses with the cortex).  You can really see that the axon and dendrites have lots of branches and each of those branches may have multiple synapses to other neurons.  This is why neurons are often compared to trees with their branching limbs.

Thalamocortical neuron.  From Destexhe et al., 1998, J. Neuro.

The authors compared the morphology of thalamic neurons from control rats to those that had their whisker trimmed.  The neurons corresponding to the  trimmed whiskers had considerably shorter and less branched axons.  Remember, these neurons in the thalamus are no longer receiving signals from the whisker, and in just three days they started to retract.  This often happens in the cortex, where an unused area of the brain will just shrink up or get taken over by other neurons.  This is the first time this has been shown for a non-cortical region of the brain. 

Functional compensation

The shortened axons are obviously making fewer synapses with cortical neurons, so these neurons should be less active.  However, when they recorded electrical activity, there was no difference in L4 cortical cells in the trimmed mice compared to controls.  The authors investigated this more thoroughly and looked at synchrony between cells.  Neurons that are active at the same time will often add up their signals at the next connection, so this is another way of looking at activity in the brain.  The trimmed mice had more synchronous cortical cells than the controls.  That makes no sense, right?  They have fewer synapses, so how could they be more synchronized?  Apparently there must be some form of compensation for the decrease in axon length and synaptic connections.  In other words, the remaining synapses become stronger to maintain a normal level of electrical activity.  We call this process homeostasis, which happens at many different levels in our bodies (temperature regulation, blood sugar, etc).

To summarize, trimming the whiskers results in less signaling to the whisker area of the thalamus.  As a result, the thalamic neurons become shorter and less branched.  They make fewer synapses onto the cortex, but it doesn’t matter because these synapses increase their strength to maintain a physiological activity level. 

The important point here is that adult neurons can undergo structural plasticity (shorter axons) and functional plasticity (strengthening of synapses) as a result of experience (or lack thereof).  These changes happened really quickly – only three rat days.  The authors conclude that “thalamocortical input to cortex remains plastic in adulthood, raising the possibility that the axons of other subcortical structures might also remain in flux throughout life.”  There’s hope for us after all!

This blog title was somewhat inspired by the Radiohead song "Fake Plastic Trees".  Oh the 90's.