Human Dendrites: Exploring the ground truth of neuronal processing
- Team performs direct patch clamp recording of individual human neurons
- Human neurons have longer dendrites than rat neurons
- This affects their integrative properties
Using human tissue resected from the brains of epileptic patients the scientists performed patch clamp electrophysiology experiments to explore, compare and contrast the differences in neuronal processing between rodents and humans.
The scientists were able to obtain the tissue by collaborating with neurologist Sydney Cash at Massachusetts General Hospital. Cash routinely removes a small section of anterior temporal lobe as he performs his surgeries to treat medication-resistant epilepsy patients. As soon as the tissue was resected it was placed into artificial cerebrospinal fluid in a cooler to prevent tissue de-oxygenation and cell death as it was transferred from the operating theatre at Massachusetts General to the lab at the McGovern Institute.
There, it was mounted onto a stage and sliced into 300 microns thick tissue sections for electrophysiological recording.
Credit: McGovern Institute for Brain Research at MIT, YouTube
Human neurons are bigger, with longer dendrites
Importantly, patients were pre-screened prior to using their brain tissue to ensure that, apart from their Epilepsy, there was no other underlying neurological condition that could impact on findings.
The scientists then set about their job of comparing human cortical layer 5 neurons in the slices of anterior temporal lobe with those of adult rat layer 5 neurons from the rat’s temporal association cortex, an area of rat brain with a similar function to that of the human anterior temporal lobe.
They immediately spotted differences, and some important similarities.
Explore: Complete electrophysiology rigs here
Firstly, as expected, the human neurons were larger, over double the size of rat brains. They were also quieter, not exhibiting the same amount of electrical excitability as their rat counterparts. Rat neurons fired action potentials in high frequency bursts of more than 150 spikes per second, whereas less than 10% of the human neurons exhibited burst firing.
Secondly, to understand how human neurons integrate incoming information from their dendritic trees, given their distance from the somas compared to rat neurons, they explored the cable properties of the apical dendrite. These are the thicker prominent dendrites which extend from the apex of the pyramidal neuron somas. They performed whole cell dendritic recordings at different positions on the dendrite up to 1,834 microns (almost 2 mm) away from the soma. Interestingly, they showed that, despite the human apical dendrites being much longer, they exhibited similar properties to the rat neurons, albeit over a greater distance. A finding that was equally surprising and reassuring, given that drastic differences between humans and rats would question their suitability as a model organism for neuroscience research.
However, they did find a significant difference in the input resistances of distal dendrites. Input resistance is a function of how much influence an ionic current will have on the membrane potential, and will depend on the ion channels that are expressed and open in the membrane. According to Ohm’s law the membrane potential (V) is a product of the current (I) divided by the input resistance of the membrane (R).
Therefore, if the membrane has lots of open channels that ions can easily move through, it will have a low resistance, meaning more current will be needed to depolarize the membrane and excite the cell.
In rats, they found that input resistance dropped with distance from the soma, yet it was significantly increased in the distal dendrites of human neurons.
Thirdly, exploring the cable properties further, they performed an experiment where they stimulated at one end of the apical dendrite and recorded towards the soma. They did this over similar distances in the rat and human dendrites to aid comparison. The scientists found that the forward propagation of electrical activity towards the soma was attenuated to the same degree in both rat and human neurons. However, the low impedence of the human dendrites meant that when they swapped round and stimulated at the soma end, the back propagating electrical activity was attenuated to a lesser degree in the human neurons compared to rat.
Human neurons are more compartmentalized
What does this mean for the neurons? These electrical features of the human cells mean the different parts of the neurons are compartmentalized. Meaning, the electrical activity in the soma does not have much influence on the excitability of the dendrites and vice versa. To further prove this, the scientists silenced the rat neuron somas by clamping them at a negative membrane potential. This recreated the human neuron conditions by electrically separating the soma from the dendrite. They then measured action potentials in the dendrites and saw their waveform shape had now changed and they were similar to those seen in human neurons.
What does this mean for our understanding of the brain? It means that we now have an understanding, at least in these layer 5 neurons, of how cell shape or size differences can influence the electrical excitability and integrative properties of neurons.
As theorists use data to predict how neurons respond to incoming signals they can better predict the impact of size and ion channel location on the electrical properties of neurons.
It also underscores the similarities between rodent and human brains, showing that they are a good model organism for investigating the brain and behavior.
Evolutionarily speaking, it could also mean that we have developed these longer dendrites and arrangement of ion channels throughout evolution to enable this compartmentalization, and this could underlie our higher levels of intelligence.
An important caveat highlighted by the authors in their study is that the human and rat tissue were not obtained in the same way, and the anesthetics exposed to the human brain tissue could influence dendritic integration.
If there are to be further comparative studies between model organisms and humans, scientists will have to address this issue, somehow.