Tag: Neurotransmitters

Biology

Brain Size and Intelligence

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Not too long ago, I was reading about the differences between the human brain and the brains of chimpanzees. It got me thinking about how we as humans somehow possess a greater level of intelligence than primates (at least, that we’ve observed) despite similar brain morphologies.

Mainly to satisfy my own curiosity, I wrote a piece about brain size and intelligence in humans versus other primates. It’s been written in a bit of a pop science style (thought it was worth giving it a try).

Enjoy!

 

To what extent is higher-level intelligence in humans (relative to primates) attributable to brain size (cm3)?

 

Outline

  1. Introduction
  2. Background Information
  3. Discussion
    1. Immediate implications of a larger brain
    2. White matter and grey matter
    3. The cranial radiator hypothesis
    4. Neurotransmitters and GLUD2
  4. Conclusion

 

Introduction

Human civilisation can be traced back through millennia, from the time of the Mesopotamians and Aztecs, to the world as we know it today. As humans, we have formed cultures and traditions that have survived for centuries. We have created areas of knowledge, like science and literature, for which we have designed frameworks and sub-domains for people to produce more knowledge. We build skyscrapers, each taller than the last, we ponder over investments, driven to earn, and we perform experiments, always eager to expand our understanding of the world around us.

Our ability to do all of these things has been well established, but why is it that the other animals that belong to the primate order cannot perform the advanced cognitive functions that underwrite those processes?

The answer is simple and somewhat intuitive. Of the discovered species of animals on the planet, we display the greatest capacity to process and integrate large amounts of incoming sensory information, and compare this new information with the existing information that we hold. We also can think conceptually, as well as in abstract terms. In short, we display higher-level intelligence.

So how did this unique intelligence that humans possess come about? Why is it that we can feel that almost electrical tension in the denouement of Macbeth, and an orang-utan cannot?

This essay seeks to evaluate the extent to which higher-level intelligence in humans (relative to primates) can be attributed to brain size by considering the primate order and looking at how human brains in particular have evolved.

 

Background Information

First, let us establish some facts about the primate order. As we can see from the cladogram below, humans and chimpanzees both diverged from gorillas before splitting into two separate species. Interestingly, out of all the great apes, humans are outliers in terms of chromosome number; we have 23 pairs of chromosomes whereas the rest of the great apes have 24 pairs. Our second chromosome was formed millions of years ago from the end-to-end fusion of 2 ancestral chromosomes (Ridley, 2000)

cladogram

Following this divergence from the great apes (through the fusion of the 2 ancestral chromosomes), the animals in the homo genus (which initially started as australopithecines) underwent periods of evolutionary change, which gave rise to several distinct features, the most prominent of which is encephalisation – an increase in the volume of the brain. During the evolution of Homo sapiens, it is estimated that our brains were adding 150 million new neurons to its own vast array of neural circuitry every 100,000 years (Matt Ridley jovially labels the scientist who calculated this figure “a mathematical masochist”).

To translate this from the cellular to the physiological, the volume of the human brain increased nearly threefold, to its present volume of approximately 1400cm3 (Hofman, 2014). At the same time, the volume of grey matter and white matter in the brain increased, in conjunction with further cortical folding (the folding of the cerebral hemispheres). The brains of the great apes and primates, on the other hand, tend to be far smaller (350-450cm3), but display similar patterns of organisation in the brain; they too have the forebrain, which holds the cerebrum, the midbrain, in which the limbic system resides, and the hindbrain, where the medulla oblongata and cerebellum are found (Hofman, 2014).

 

Discussion

Immediate implications of a larger brain

Let us now move on to the question at hand, and consider the extent to which we can attribute the intelligence of modern day humans to brain size. As mentioned previously, it is clear that human brains are larger than the brains of other primates. So what does this higher brain size translate into?

The most obvious answer to this question is that a larger brain would have a higher number of functional neurons, as substantiated by the fact that humans have 86 billion neurons, whereas chimpanzees have 26 billion (Hofman, 2014). In particular, humans have a larger cerebral cortex, the centre for higher order processing in the brains of primates. The immediate result of a larger cerebral cortex is a greater number of neurons and nuclei dedicated to specific tasks, thus increasing the potential of the human brain to carry out a greater number of cognitive functions than our primate cousins.

White Matter and Grey Matter

However, it may not be the size of the cerebral cortex that has given the human brain an intellectual advantage over other hominids and primates. 50% of the human cerebral cortex (by volume) is composed of grey matter (Hofman, 2014). Grey matter consists of sections of the central nervous system that carry the cell bodies of neurons, their axons, their dendrites, the capillaries that nourish them, and most importantly, their synapses. The synapses are the points of communication between individual neurons. They are fluid filled gaps over which neurons will exchange chemical information to determine the direction over which an impulse will be propagated. In essence, they are connection points between different neurons, which may be associated with different nuclei (clusters of neurons with similar functions) in the brain, enabling different impulses from different parts from the brain to be linked and integrated to be sent to other nuclei. This forms the basis for higher order thinking – it is based on the summative effect of multiple pre-synaptic neurons producing a response in a particular postsynaptic neuron. In plain English, it allows us to synthesise new knowledge from multiple pieces of existing knowledge.

To sum up, the higher proportion of the human brain (relative to other primates) devoted to grey matter supports the argument that the size of the human brain may not be the main factor that has led to human intelligence.

However, we have to consider the fact that the human brain is, inexorably, larger than the brains of other primates. As a result, the higher proportion of the cerebral cortex dedicated to grey matter physically manifests as a higher volume of grey matter and therefore, a greater number of synaptic junctions, which forms more complex circuitry in humans than in primates. Hence, we have to consider the proposition that the higher-level intelligence that humans possess can be indirectly attributed to brain size.

Another point in favour of the latter argument relates to the proportion of white matter in the human brain. White matter, unlike grey matter, is comprised of the elongated axons that connect different nuclei. Hence, we can think of grey matter as holding the switches in the brain with the white matter forming the “wires” that connect a series of “switches” together.

As we can see below, the proportion of white matter as a function of brain volume in primates increases at a near exponential rate with brain volume.

IMG_0863

Does this correlation imply a causative influence conferred by brain volume? To answer this question, we must once again venture into the history of the evolution of the human brain.

As we know, there was a definite increase in the volume of the human brain as we diverged from primates. With this larger volume came with it a diaspora of different nuclei distributed around the vast neural landscape of the brain. This created a need to generate high interconnectivity between different nuclei, with short conduction delays. To strike a compromise between these two factors, the human brain evolved to create greater interconnectivity between nuclei by dedicating more of the brain to white matter, and reduced conduction delays by developing myelinated axons in the white matter.

Due to the development of this system, humans are able to integrate information from multiple sources seamlessly, establish patterns, and generate new information rapidly. We can therefore attribute these characteristics, which form part of what we define as “human intelligence,” to evolutionary changes that were necessitated by an increase in brain volume.

 

The cranial radiator hypothesis

On the other hand, brain size may not necessarily be the main reason why humans are the most intelligent primates. The human brain can only work as hard as it does, firing off countless action potentials in a second, because heat, a metabolic waste product of its activities, can be removed at such a rate that it does not inhibit brain function.

Unlike most other primates, humans have a shunt of veins that flow close to the surface of the cerebral cortex, helping to remove excess heat generated by the activity of the 86 billion neurons in the brain (Falk, 1990). This cranial radiator removes temperature as a limiting factor and facilitates greater neuron activity per unit time, thus increasing processing speed and possibly contributing to the development of human intelligence.

 

Neurotransmitters and GLUD2

Let us consider something we have touched on briefly, the neurochemistry of the brain, specifically the neurotransmitters found in primates. How do the neurotransmitters used in the human brain differ from those found in other primates? The minor role the size of the human brain plays in the development of human intelligence is most clearly illustrated when one considers the neurochemistry of the human brain. Although we share a large number of our neurotransmitters with other primates, we have different mechanisms to recycle them for later use. Could this be main reason why humans have higher-level intelligence than primates?

Take for example, the GLUD2 gene. The human version of the gene differs from that of other primates by simply 2 amino acids, but this change is sufficient in producing a more efficient version of the glutamate dehydrogenase (GDH) enzyme that GLUD codes for (Bradbury, 2005). GHD can catalyse the decomposition of glutamate (a neurotransmitter) into alpha ketoglutarate, or catalyse the reverse reaction. Thus, the more efficient GDH produced by the human GLUD2 gene gives rise to greater glutamate turnover, which could have facilitated a greater rate of synaptic transmission in humans relative to other primates.

 

Conclusion

Let us circle back to the question posed at the very beginning of this essay – to what extent can human intelligence relative to primates be attributed to brain size? Weighing all of the factors we have considered, it becomes clear that our larger brain size is, inexorably, the main reason we have a greater capacity to interpret and analyse information relative to primates. There is also an ineluctable correlation between brain size (cm3) and the proportion of white matter as well as grey matter in the brain. As a result, the larger size of the human brain allows for greater interconnectivity (brought about by a larger amount of white matter) between greater numbers of nuclei (conferred by a larger amount of grey matter).

Although the cranial radiator hypothesis accounts for higher neuronal activity, such activity would likely be impossible without the vast number of neurons already present in the brain, which exist in such high quantities due to the large volume of the brain.

However, the role of genes in giving rise to human intelligence through influencing the behaviour of neurons cannot be understated. Up to 100 genes are expressed differently in the human brain than in the brain of a chimpanzee. This piece of evidence lends itself to the idea that human intelligence could be a product of genetic factors, rather than morphological features. On the other hand, the two may not be mutually exclusive, as these genetic factors could also be responsible for the morphological differences in the brains of humans and other primates.

 

References + Further Reading

  1. Hofman, M.A., 2014. Evolution of the human brain: when bigger is better. Frontiers in neuroanatomy, 8, p.15.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973910/

  1. Falk, D., 1990. Brain evolution in Homo: The “radiator” theory. Behavioral and Brain Sciences, 13(2), pp.333-344.

https://www.cambridge.org/core/journals/behavioral-and-brain-sciences/article/brain-evolution-in-homo-the-radiator-theory1/DC2C8FEF97A35B699DFE7BFEC2093CA9

  1. Ridley, 2000. Genome. Howes.
  2. Bradbury, J., 2005. Molecular insights into human brain evolution. PLoS Biology, 3(3), p.e50.

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0030050

 

 

 

 

 

 

Biology

Phototransduction

ardonp5 Comments

An interesting concept I’ve stumbled across during my reading into neurobiology is that a neurotransmitter need not be exclusively excitatory or inhibitory. In fact, a prime example of this would be glutamate in phototransduction, the process by which the stimulation of photoreceptors by photons triggers the propagation of an action potential across the optic nerve.

retina diagram

A pretty good minimalist diagram from Bioninja that shows the basic structure of the retina

 

The behaviour of photoreceptors in the dark

In the dark, we find that the photoreceptor cells have a relatively high membrane potential (-40mV). This membrane potential comes about because, in the dark, these cells have high concentrations of a molecule called cyclic guanosine monophosphate (cGMP), which binds to cGMP gated Na+ and Ca2+ channel proteins to allow their entry by facilitated diffusion into the photoreceptor, hence the cell to exhibit a depolarised membrane potential.

This has the effect of keeping voltage gated Ca2+ channels between the synaptic knob and the main body of the photoreceptors open, thus facilitating the movement of glutamate across the synaptic cleft and allowing it to bind to receptors on the post-synaptic bipolar cell.

This is where things get interesting. Glutamate is typically a fast-acting, excitatory neurotransmitter, but in this particular case, it behaves as a slow-acting inhibitory neurotransmitter. I initially thought it was able to do this by binding to a glutamate gated anion channel.

As it would seem, glutamate activates a cytoplasmic guanosine (G) protein by binding to receptors on the membrane of the bipolar neuron. This G proteins initiates a cascade of reactions that reduce the cytoplasmic cGMP concentration, thus reducing binding of cGMP to cGMP gated cation channels that need to be open to trigger depolarisation.

As a result, in the dark, the bipolar neuron is hyperpolarised (its membrane potential is approximately -65mV) due to the glutamate released by the depolarised photoreceptors. The bipolar cell’s inability to depolarise is what inhibits any impulses from being transmitted from the eye to the brain under pitch-black conditions.

What is fascinating is how the membrane potential across the bipolar cell changes when light strikes the photoreceptor beneath it.

 

The behaviour of photoreceptors under illumination

In regions called receptor disks, photopigments are stored within photoreceptor cells. In rods, the main photopigment is rhodopsin – a molecule associated with retinal and a number of opsin polypeptides. When retinal absorbs a photon, its configuration changes from its 11-cis isomer to an all trans isomer. This initiates a series of reactions which result in the activation of the intracellular signalling protein transducin (from which phototransduction derives its name).

Transducin in turns activates phosphodiesterases which hydrolyse cGMP molecules. This has the effect of reducing the concentration of cGMP in the photoreceptors, thus reducing binding to cGMP gated Na+ and Ca2+ channel proteins, thus resulting in hyperpolarisation of the photoreceptor cell.

This decrease in membrane potential closes the voltage gated Ca2+ channels, reducing the concentration of Ca2+ in the synaptic knob. As a result, the quantity of glutamate released sharply decreases, leading to the depolarisation of the bipolar cell, triggering the propagation of an action potential along the axons of the ganglia.

Moving away from neurotransmitters momentarily, let’s look into how cytoplasmic Ca2+ concentrations can influence the extent to which photoreceptors respond to light.

 

Sensitivity to Light Intensity

Generally, photoreceptors display diminishing sensitivity to illumination as light intensity increases. When the Ca2+ concentration in the photoreceptor decreases, it triggers a small change in the phototransduction cascade, by initiating the upregulation of the enzyme that produces cGMP and also increasing the affinity the cGMP gated Na+ and Ca2+ channels have for cGMP. This reduces the sensitivity of the photoreceptors to any increases in illumination by requiring a larger number of activated photopigments to reduce the cytoplasmic cGMP concentration to a low enough level such that the membrane potential can be decreased.

 

Recycling of retinal

With respect to the photopigments, there must always be a sufficient quantity of viable photopigments in the receptor disk. To ensure that this is the case, following the depolarisation of the photoreceptor, the protein arrestin binds to activated rhodopsin molecules, preventing them from binding to transducin and facilitating their movement to the pigment epithelium.

In the pigment epithelium, a series of enzymatic reactions convert the all trans retinal molecule in rhodopsin into its 11-cis form. Following this, the rhodopsin molecule moves back into the receptor disk. This system effectively allows for the recycling of previously activated photopigments and maintains the presence of inactivated photopigments in the receptor disk.

 

Conclusion

Phototransduction is an example of a process whose beauty lies in the rationality of its design – it continuously regenerates new components, gives rise to variable light sensitivity, and most importantly, allows us to see.

Biology · Chemistry

What’s a good example of an interesting amino acid?

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glycine.png

What a fascinatingly simple molecule. We typically assume that long, complex molecules with equally long names have the most interesting roles to play in Biochemistry, but this non-essential amino acid in itself offers the converse argument. So what makes glycine so special?

Firstly, its behaviour in acid-base reactions is two-fold; it can act as an acid or a base. In low pH solutions, it is protonated very easily, with a pKa of 2.4, to form CH­2COOHNH3+, whereas in high pH solutions, it forms CH­2NH2COO­–, with a pKb of 4.4. This is one of the features that allows glycine to be featured prominently in a wide myriad of proteins (interestingly, collagen is 35% glycine) and polypeptide chains; depending on the pH of the surroundings, the same protein could take up different conformations, partially due to the amphoteric nature of glycine.

Now, let’s consider a more interesting role that glycine plays in mammalian systems. It acts as an inhibitory neurotransmitter – a substance that, when it binds to ionotropic post-synaptic receptors (transmembrane proteins that allow specific ions to enter a cell), results in the generation of an inhibitory post synaptic potential. What is interesting is the mechanism that initiates this. When glycine moves across the synaptic cleft and binds to ionotropic receptors on chlorine channels, said channels open, resulting in an influx of Cl– ions into the post-synaptic neuron. This has the effect of reducing the cell potential far below the resting potential and even further below the threshold potential, creating an inhibitory post-synaptic potential. It is inhibitory because it reduces the likelihood of the threshold potential being released when a non-inhibitory neurotransmitter binds to the post-synaptic neuron, thus inhibiting the propagation of an action potential across a synapse.

Aside from playing a role in the regulation of the central nervous system, glycine is also broken down through a series of metabolic pathways to provide the C2N subunit for purines in DNA. 2 ways in which glycine is broken down are especially interesting, because of how they aid another key biological process in the human body – aerobic cellular respiration. When glycine reacts with tetrahydrofolate and NAD+ in its most common catabolic pathway, it ends up forming NADH. In another pathway, it is broken down to form serine, which is subsequently converted to pyruvate. Both NADH and pyruvate play key roles in aerobic respiration; the former is oxidised in the electron transport chain to facilitate oxidative phosphorylation and the latter is broken down in the link reaction to form acetyl coenzyme A, which is used in the Krebs’s cycle to produce NADH and FADH2.

Finally, it is the only amino acid that has been found in space, something that, arguably, could be traced to its simple structure.

Considering the breadth of roles glycine plays in mammals, its fascinating chemistry and presence in space; it certainly is an interesting amino acid.