- Human neurons have far fewer ion channels than other mammalian neurons, according to a group of experts.
- The reduced number of ion channels may contribute to human brain function being more efficient.
- The results of the neuroscientists pave the path for more investigation into the evolutionary forces that underpin this divergence.
The central nervous system, which includes the brain and spinal cord, is made up of neurons. Electrical impulses and chemical signals are used to communicate.
There are around 100 billion of these cells in the human brain.
The activation of ion channels, which govern the passage of mineral ions such as potassium and sodium, generates neuronal impulses. In mammalian brains, the density of ion channels in the neurons grows as the size of the neurons increases.
This was not the case for human neurons, much to the amazement of neuroscientists from the Massachusetts Institute of Technology in Cambridge and Harvard Medical School in Boston.
Their findings will be published in Nature in November 2021.
“These findings have important implications for understanding our outstanding cognitive abilities and the challenges [that] therapies derived from animal models face in human clinical trials.” said Lou Beaulieu-Laroche, Ph.D., a neuroscientist and the study’s lead author, in a recent LinkedIn post.
This study represents Dr. Beaulieu-“greatest Laroche’s scientific achievement.”
Exploring allometric relationships
Neuronal input-output properties are determined by neuronal size, which impacts how likely a neuron is to “fire” in response to a certain degree of input from neighboring neurons. Neuron size also varies greatly between mammalian species.
Brain samples from people with epilepsy who had had neurosurgical treatment, Etruscan shrews, mice, rabbits, and macaques, among other species, were studied by the study.
“characterize layer 5 cortical pyramidal neurons across 10 mammalian species to identify the allometric relationships that govern how neuronal biophysics change with cell size.” the researchers said.
The authors chose these group of neurons because they are “reliably recognizable” and have been researched extensively by scientists. The study of how an animal’s traits change with its size is known as allometry.
The researchers were able to examine different neuronal sizes and cortical thicknesses across the mammalian kingdom by investigating ten species.
The scientists concentrated on two types of ion channels in particular: hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels. They focused on these two because they are easy to access and have a significant impact on neural networks.
Exception to the patterns
Except for humans, the neuroscientists noticed a “construction blueprint” that was identical across all species. They express themselves as follows:
“We observe conserved principles that control the conductance of voltage-gated potassium and HCN channels in 9 of the 10 species.” Membrane ionic conductances are higher in species with larger neurons and, as a result, a lower surface-to-volume ratio.”
Conductance refers to the capacity of ions to easily pass through ion channels in the membrane of a neuron.
Human neurons do not have the same allometric patterns as the other nine mammals, according to Dr. Beaulieu-Laroche and colleagues. In human neurons, however, voltage-gated potassium and HCN channel conductances were significantly lower.
These findings demonstrate “conserved evolutionary principles for neuronal biophysics in mammals, as well as notable features of the human cortex.”
Enhanced computational potential
Human neurons are larger than those of other mammals, according to some of the authors of this study.
However, the current findings indicate that human layer 5 neurons “are not just large […] but are fundamentally distinct.”
Keiland Cooper, a neuroscientist from the University of California, Irvine, spoke with Medical News Today about the latest study. He was not a part of this study.
Cooper was intrigued that human layer 5 neurons were distinct in terms of ion channels. He speculated, “Perhaps the human brain diverges from the pattern to meet a changing energy demand, as opposed to other species.”
The lower membrane conductance of human neurons, according to Dr. Beaulieu-Laroche and his co-authors, allows the cerebral cortex “to allocate energetic resources to other aspects of neuronal function (e.g., synaptic transmission) that are more computationally effective.”
To put it another way, the energy saved by having fewer ion channels could be used to help the human brain perform other, more difficult tasks.
‘Novel and important locus’
This study presents “a fresh and important locus for future investigations into the human condition,” according to its authors.
The neuroscientists want to know where the excess energy in human neurons goes. They also want to see if there are any genetic modifications that allow human neurons to become so effective.
Furthermore, these scientists wonder if primates that are closely related to humans have lower ion channel density as well.
Cooper is also looking forward to these discoveries, as he told MNT:
“Cross-species studies like these are terrific, and due to the methodological difficulties, are done far less often than they probably should be.”
“A study like this will raise a whole new set of issues that must be investigated: What could be the source of the distinctions between humans and other animals? Are there any distinct genetic markers or developmental milestones that separate species? What functional implications might there be, or does the brain adjust in some way?”
Cooper added, “I’m really excited to see the follow-up work that will result from this study.”
The future
The researchers don’t know why “[ion] conductance per volume is lower in humans, or why it is conserved in all other studied species,” according to the researchers. This will necessitate a lot more investigation.
The researchers note out that the disease history and therapies of the persons who provided the samples could have influenced the study’s outcome.
“Previous studies with extensive patient history and surgery types failed to observe significant correlations between disease etiology and dendritic morphology or synaptic plasticity.”
“Previous studies with extensive patient history and surgery types failed to observe significant correlations between disease etiology and dendritic morphology or synaptic plasticity.”
On this point, Cooper agrees; he told MNT, “I think the authors create a compelling case for the human neurons to be representative, however, further work to dissociate these differences will need to be completed to confirm this single study.”
As for next steps, the authors conclude their paper by noting:
“Future research is needed to establish the evolutionary pressures underpinning these different traits and their importance to human brain function,” says the researcher.
