NEURONS & SYNAPSES

NEURONS & SYNAPSES

HOW MANY NEURONS?
The vast majority of books and documentaries about the human brain cite the number of neurons to be 100 billion. While writing a previous book, I searched for the source of this claim and discovered that apparently none exists. It does not seem to be supported by evidence. The 100-billion-neuron claim seems to be nothing more than an agreed-upon guess that everyone keeps repeating.

Fortunately, a team of scientists decided to find out just how many neurons a typical human brain really does contain. They couldn’t just count them one by one, of course, because that would take centuries. So they liquefied brains in blenders—one at a time—made sure the neurons were equally distributed in the resulting fluid, and then counted sample portions. This allowed them to extrapolate a total neuron count for the entire brain. The total number of neurons for a human brain the researchers came up with was 86 billion.50 This is significantly lower than 100 billion but still an astonishing amount. The surface area of this many neurons—just one brain’s worth—has been estimated to be the equivalent of more than three football fields.

From ‘At Least Know This: Essential Science to Enhance Your Life’, by Guy P. Harrison (Prometheus Books)


The core component of the nervous system in general, and the brain in particular, is the neuron or nerve cell, the “brain cells” of popular language. A neuron is an electrically excitable cell that processes and transmits information by electro-chemical signalling. Unlike other cells, neurons never divide, and neither do they die off to be replaced by new ones. By the same token, they usually cannot be replaced after being lost, although there are a few exceptions.

The average human brain has about 100 billion neurons (or nerve cells)

Each synapse functions like a microprocessor, and tens of thousands of them can connect a single neuron to other nerve cells. In the cerebral cortex alone, there are roughly 125 trillion synapses, which is about how many stars fill 1,500 Milky Way galaxies.

One synapse, by itself, is more like a microprocessor--with both memory-storage and information-processing elements--than a mere on/off switch. In fact, one synapse may contain on the order of 1,000 molecular-scale switches. A single human brain has more switches than all the computers and routers and Internet connections on Earth.

Each neuron may be connected to up to 10,000 other neurons, passing signals to each other via as many as 1,000 trillion synaptic connections, equivalent by some estimates to a computer with a 1 trillion bit per second processor. Estimates of the human brain’s memory capacity vary wildly from 1 to 1,000 terabytes (for comparison, the 19 million volumes in the US Library of Congress represents about 10 terabytes of data).

http://www.human-memory.net/brain_neurons.html

Researchers in Germany have created an exquisitely detailed three-dimensional model of a nerve terminal

https://www.youtube.com/watch?v=icey1NYP7Pw

The electrochemical jelly inside your head contains something like one quadrillion synapses, the junctions at which nerve cells talk to one other by converting electrical signals into chemical ones and then back again. They have two components (sometimes three): the nerve terminal of one cell, which stores and releases neurotransmitter molecules, and the 'post-synaptic' membrane of another cell, which contains binding sites for the neurotransmitters.

Synapses are miniscule – nerve terminals are about one thousandth of a millimetre in diameter, and the space between them and the membrane they contact a mere 20-40 millionths of a millimetre wide – and are densely packed in the grey matter of the brain tissue, making them notoriously difficult to study. But researchers in Germany have now created an exquisitely detailed model of a nerve terminal, which shows the distribution of 300,000 individual protein molecules in the nerve terminal in atomic detail, and hints at how neurotransmitter release is regulated.

Inside the nerve terminal, neurotransmitter molecules are stored in tiny spheres called synaptic vesicles, which are "docked" in an "active zone" just beneath the cell membrane. When a nervous impulse arrives at the terminal, it causes a few of the vesicles to fuse with the membrane and release their contents. Later on, the spent vesicles are recycled – they are pulled back out of the membrane, re-filled with neurotransmitter molecules, and eventually re-used.

At any given terminal, vesicle fusion can occur hundreds of times per second, as trains of impulses arrive one after the other. The whole process of vesicle docking, fusion and recycling is therefore tightly regulated, to ensure that there is a ready supply of vesicles that can fuse in quick succession and maintain the rapid bursts of neuronal activity.

http://medicalxpress.com/news/2014-05-highly-3d-individual-neural-synapse.html



(Medical Xpress)—A team of researchers in Germany has created a very highly detailed 3D computer model of an individual rat synapse showing the distribution of approximately 30,000 proteins involved in the process of sending a message from one neuron to another. In their paper published in the journal Science, the team describes how they combined several imaging techniques to create the model, and what it is able to display.

In simple terms, neurons transmit messages between one another via synapses—parts of neurons dedicated to converting electrical signals to chemical signals and vice versa. Synapses generally come in two varieties, the kind that send and the kind that receive signals. Neurons have both kinds of course, which allows them to send and receive messages. To send a message, electrical signals from the neuron travel to the sending synapse where they encounter vesicles. Prodded by the electrical signal, the vesicle releases chemicals called neurotransmitters into the space between (the cleft) the sending synapse on one neuron and the receiving synapse on another. The receiving synapse then processes the message and responds based on the signal it receives.

In the sending synapse, the vesicles are made ready for action by being loaded with neurotransmitters and locked into position. Once they release their cargo, they are moved back out of the way so other vesicles can work while they are being refilled—once ready, they are again placed into position and put to use. This constant recycling goes on over and over, allowing neurons to process a steady stream of messages. In this new effort, the team in Germany has used a variety of microscopic methods to capture the structure of the sending synapse and what happens to it as recycling occurs and messages are sent.

http://www.sciencemag.org/content/344/6187/1023

Proteins in the Neuron Shape is Function

Despite great difficulties in understanding folding, for proteins in the neuron shape is function.

At a billion tries per second, it takes ten billion years to test all protein folding possibilities in an average sized protein.

Improbably, the protein accurately folds in milliseconds.

The final shapes of the proteins determine the functions throughout the neuron.

Mental events flow through the interlocked protein machines.

The Neuron is a Very Large Complex Cell



The neuronal signal is sent through the protein structures. Some think it is just an electrical signal, but there is, in reality an entire elaborate structure, a veritable city built in proteins, which mediates the changes that occur in the neuron. These alterations in the neuron are known as plasticity and the signaling of information related to mental events.

Proteins, discussed in the previous post, have very specific and accurate shapes to provide load bearing, force generation, chemical reaction enhancing, infection protection, and information signaling. A previous post described the remarkable microtubules, a set of LEGO pieces that provide a language of function in the neuron. As dendrites and spines bud, as axons grow, the microtubules grow and contract to provide the necessary structure. As structures are built in the neuron, the microtubule becomes a highway with motors providing transit for energy producing mitochondria, and all types of material for construction, repair, and signaling.

To provide the necessary generation of forces in the neuron, proteins expand, contract, bend, turn, twist, and flex to meet these varied needs. The protein’s shape, and therefore the folding of the protein, is the critical element in all of these processes. This shape is somehow determined by code that is regulated from millions of genetic factors and edited multiple times in the process. The code evolves over time, often through copying and altering entire sections of DNA that represent protein shapes

Physical Forces in Cells
Mechanical forces acting on the cells influence all of the major functions of neurons. These functions include cell division, migration and adhesion, electric flow through ion channels in the membrane, and transportation of neurotransmitters in vesicles.

Specific mechanical events in the neuron include the change in shape of the membranes as the electrical signal travels through. The unique merging (without breaks) of the vesicles carrying neurotransmitters with the membrane is a mechanical event that requires elaborate, but flexible and changing, scaffolding to connect and disconnect the vesicle and membrane.

A previous post discussed how new synapses related to new mental events are often in close proximity to other synapses of related events. The spines that grow from dendrite buds forming synapses appear to “twitch.” This mechanical movement is now thought to be critical to sending messages between adjacent dendrites. Cells sense mechanical stimuli, transduce this energy, and then respond, all through the shapes of the proteins. This is a form of neuroplasticity.

Brain Mechanics
The brain is extremely soft and elastic, one of the softest materials in the body. Surprisingly, the stiffness of the brain varies between regions, and these properties change in disease, all related to the shape of the proteins. Stiffness is related to many different factors, each with their interlocking shapes, related to the membrane, cytoskeleton, extra cellular matrix, surface cell adhesion proteins, and membrane embedded ion channels. It is the interlocking shapes that direct the forces and information flowing through the neuron.

Plasma Membranes
Membranes are dynamic structures that change moment to moment and respond to forces with changes in shape. The membrane is not sensitive to compression, but is very susceptible to bending. The bending properties enable merging with vesicles releasing neurotransmitters, and reabsorbing them back into the neuron after the signal. The bending can also be beneficial while growing new axons, dendrites, spines and synapses. The membrane, meanwhile, is hardened by skeletal elements such as actin protein structure.

The membrane is a layer of fatty material, which is hydrophobic (water fearing) having no water in the middle. With this separation of watery and fatty regions, watery inside the cell and outside in the extra cellular space, fatty in the membrane itself, it keeps a definite demarcation between internal events and extracellular matrix events.

There are many large protein molecules embedded in the membrane communicating information and forces between the outside and inside of the neuron. Some of these large embedded proteins are receptors that trigger mechanisms on the other side. Some are the channels that let ions and other molecules flow in and out, creating the electric current and supplying materials.

Cytoskeleton
The substance on the inner part of the cell membrane is called the protoplasm. Its structure is determined by protein shapes formed by molecules like actin and microtubules. The actin structure gives stability to the membrane when it is merging with vesicles to deliver neurotransmitters. Actin gives strength to the bending and shape changing of the membrane when a new dendrite or axon is growing. Actin accumulates in a region at first in the form of small particles called G actin. When there is sufficient density of particles it forms long connected molecules polymers, called F-actin, which is very strong. Branches between these fibers make it even stronger.



The leading edge of the axon, the growth cone, is filled with skeletal structural molecules, as it travels to find its mate in a synapse. The actin grows by polymerization at the leading edge on the inside of the membrane, while on the outside of the neuron adhesions form with elements of the extracellular matrix through adhesion molecules, which are involved in guiding the axon on its very lengthy journey toward other neurons, perhaps in totally different regions of the brain. In fact, growth cones are quite soft, which makes them very sensitive to both the actin on the inside and the adhesion molecules on the outside.

Meanwhile on the dendrite side of the synapse in the other neuron, actin is also building the budding dendrite skeleton. It is not as clear how the forces operate in the spines as in the axons.

Another molecule, the spectrins, are important in the axon and dendrite skeletons. These proteins have a spring function and combine with actin to form important scaffolding for the dendrite. Spectrins are needed to form dendrites and spines in Purkinje cells, and in hippocampus. These spectrins are critical also to stabilize nodes of Ranvier in myelinated neurons, and potassium channels in the axon.

Actin and Spectrin in Axons and Dendrites
Recently, the skeletal structures in the axons and dendrites have been imaged more successfully. These studies showed that actin formed rings around the circumferences of the axon at regular intervals to hold the shape of the axon. These rings have the appearance of a ladder. The rings are evenly spaced and then reinforced with other scaffolding molecules. Two other important proteins add to the structure. Adducin caps the actin fibers and spectrin alternates with the actin and strengthenes it.

The complex protein sodium channels fit neatly into the structure created by these other proteins.

The dendrites do not have periodic rings, but rather long filaments along the shafts and spines.

Neuroplasticity occurs by an altered synapse structure, using these structural fibers.

Microtubules and Neurofilaments
A previous post discussed the importance of microtubules for the functioning of the neuron. Microtubules are the essential highways of transport for any function, including materials, mitochondria, and sacs. A recent study showed that when traffic jams occur during the transport of essential products, some of the important cargo use multiple motors, so they can switch tracks in a jam.

Microtubules are forceful engines in some cellular processes, being the source of spindles in dividing cells. Construction forces are determined by the addition of longer microtubules or the collapse of a microtubule. They can bend but also they can break.

There are many other fibers that strengthen the microtubule track to withstand movement of multiple cargoes. Tau, an important molecule in Alzheimer’s disease, is one of the proteins strengthening microtubules. ATP energy is used to propel the kinesin motors along the microtubule.

Recently, it has been shown that microtubules do more than transport cargoes and support structures. They now appear to be involved in the regulation of spines and the production of synaptic plasticity. Previous posts have discussed how important forms of neuronal plasticity are accomplished by changes in the structures of the synapses.

Extracellular Matrix (ECM)
Outside of the membrane, protein structures hold the neuron in shape and in space. Adhesion molecules on the outside surface of the neuron connect with the matrix of the extracellular space and glia cells. A previous post showed that some of these adhesion molecules are related to immune globulins.

Reelin is a protein in the ECM that helps maintaining the synapse structure as well as the plasticity changes in the synapse, including helping ion channels, reuptake of neurotransmitters, and creating dendritic spines. There are many other proteins that support the structures – collagens, laminins, and fibronectins. While neglected in some accounts, in fact the ECM appears to be important in many diseases including seizures, and psychiatric illness.

Integrins are important adhesion molecules, implicated in psychiatric disease, that connect to the ECM. Integrins are critical to forming synapses and contribute to signals from the glia and ECM to form and maintain synapses.

Cadherins are another adhesion molecule connecting neurons to other neurons. These connections stabilize dendrite spines and other synapse structures.

Ion Channels
It is well known that mechanical pressure and tension can activate sensory systems such as in touch and hearing. Plasma membranes curve and move and respond to electrical charge (see electrical post) and these mechanical effects can stimulate ion channels. Many potassium, sodium and calcium channels are activated by mechanical change in the cell. These changes can be the addition of more protein channels embedded in the membrane. Also, when very active signaling occurs, increased merging of vesicles with the membrane when neurotransmitters are released or picked up can bend the membranes.

The Synapse – New Mechanisms
Synapses are extremely complex structures with many different elements connected in three dimensions – the skeletons of each neuron, the thousands of proteins in the post synaptic density, special adhesion molecules of the surface of each neuron connecting to the large extracellular matrix proteins.

Because all of these are connected, a force on one can influence the others. For example, the spines on dendrites might be sending forces across the structures, such as contraction of the spine, that influence the release of neurotransmitters in the pre synaptic neuron. (See picture below.) In some hippocampal cells a contraction of a spine leads to expansion of the presynaptic neuron sending neurotransmitters. Integrins become critical factors in the life of the synapse (integrins may be significant in psychiatric illness).

Neuroplasticity can occur through changes in these structures. Spines can communicate with secretion of substances, but also with mechanical forces. For example, the microtubule might span the distance of five to ten spines and can influence communication between them. The microtubule can also grow into the spine. Pushing and pulling of the microtubules and actin molecules can signal between adjacent spines.

The postsynaptic density is so complex, its exact function is not totally clear. The large number of interlocking proteins forms a disc and are integrally related to the region of the postsynaptic cell where the dendritic spine accepts messages from the synapse. Different brain regions have very different compositions in the PSD.

The Language of Shapes and Mental Events
Proteins’ shapes produce all of the neuron’s functions. The shape is determined by the correct folding, demonstrated by the low energy of a stable molecule. The interlocking shapes determine the large complex civilization of the neuron.

Shapes, however, are determined by, the extremely complex genetic process described in the posts on ENCODE (encyclopedia of DNA elements). Only 1.5% of the human DNA are in the form of genes that make proteins, whereas 30 times more (another 20%, and possibly 40%) create millions of small RNA particles that regulate the process of editing and translating the code into proteins. (see post of genetic elements)

Protein shapes are gradually altered in evolution producing innovations. These changes occur, most probably, by utilizing the 50% of the human DNA that are copies of jumping genes and viruses (see post on jumping genes). It is the commerce in pieces of DNA, each of which represents a shape of a protein, which probably allows the positive evolutionary changes that create new capabilities. Previous posts have shown that the self editing by the cell shows cellular cognitive processes – editing of DNA copying errors, editing of RNA transcripts in “alternative splicing,” and possibly editing of the new jumping gene shapes.

These shapes are the language of the cell and determine the vast array of proteins in the neuron. The coded information flows through regulatory mechanisms, protein structures and shapes, and allows the mind to use the neuron for mental events.

The commerce of evolution is shape. The language of the mind in the neuron is shape.

1) http://jonlieffmd.com/blog/proteins-in-the-neuron-shape-is-function#sthash.eHhB56FQ.dpuf