Tag: Neurons

Neuroscientists Transfer “Memories” from One Snail to Another: A Christian Perspective on Engrams

neuroscientiststransfer

BY FAZALE RANA – SEPTEMBER 26, 2018

Scientists from UCLA recently conducted some rather bizarre experiments. For me, it’s these types of things that make it so much fun to be a scientist.

Biologists transferred memories from one sea slug to another by extracting RNA from the nervous system of a trained sea slug and then injecting the extract into an untrained sea slug.1 After the injection, the untrained sea snails responded to environmental stimuli just like the trained ones, based on false memories created by the transfer of biomolecules.

Why would researchers do such a thing? Even though it might seem like their motives were nefarious, they weren’t inspired to carry out these studies by Dr. Frankenstein or Dr. Moreau. Instead, they had really good reasons for performing these experiments: they wanted to gain insight into the physical basis of memory.

How are memories encoded? How are they stored in the brain? And how are memories retrieved? These are some of the fundamental scientific questions that interest researchers who work in cognitive neuroscience. It turns out that sea slugs belonging to the group Aplysia(commonly referred to as sea hares) make ideal organisms to study in order to address these questions. The fact that we can gain insight into how memories are stored with sea slugs is mind-blowing and indicates to me (as a Christian and a biochemist) that biological systems have been designed for discovery.

Sea Hares

Sea hares have become the workhorses of cognitive neuroscience. This creature has a nervous system that’s complex enough to allow neuroscientists to study reflexes and learned behaviors, but simple enough that they can draw meaningful conclusions from their experiments. (By way of comparison, members of Aplysia have about 20,000 neurons in their nervous systems compared to humans who have 85 billion neurons in our brains alone.)

Toward this end, neuroscientists took advantage of a useful reflexive behavior displayed by sea hares, called gill and siphon withdrawal. When these creatures are disturbed, they rapidly withdraw their delicate gill and siphon.

The nervous system of these creatures can also experience sensitization, which is learned by repeated exposure to stimuli, resulting in an enhanced and broad response by the nervous system to stimuli that are related—say, stimuli that connote danger.

What Causes Memories?

Sensitization is a learned response that is possible because memories have been encoded and stored in the sea hares’ nervous system. But how is this memory stored?

Many neuroscientists think that the physical instantiation of memories (called engrams) reside in the synaptic connections between nerve cells (neurons). Other neuroscientists hold a differing view. Instead of being mediated by cell-cell interactions, others think that engrams form within the interior of neurons, through biochemical events that take place within the cell nucleus. In fact, some studies have implicated RNA molecules in memory formation and storage.2 The UCLA researchers sought to determine if RNA plays a role in memory formation.

Memory Transfer from One Sea Hare to Another

To test this hypothesis, the researchers sensitized sea hares to painful stimuli. They accomplished this feat by inserting an electrode in the tail regions of several sea hares and delivering a shock. The shock caused the sea hares to withdraw their gill and siphon. After 20 minutes, they repeated the shock protocol and continued to do so in 20-minute intervals five more times. Twenty-four hours later, they repeated the shock protocol. By this point, the sea hare test subjects were sensitized to threatening stimuli. When touched, the trained sea hares would withdraw their gill and siphon for nearly 1 minute. Untrained sea hares (who weren’t subjected to the shock protocol) would withdraw their gill and siphon when touched for only about 1 second.

Next, the researchers sacrificed the sensitized sea hares and isolated RNA from their nervous system. Then they injected the RNA extracts into the hemocoel of untrained sea hares. When touched, the sea hares withdrew their gill and siphon for about 45 seconds.

To confirm that this response was not due to the injection procedure, they repeated it by injecting RNA extracted from the nervous system of an untrained sea hare into untrained sea hares. When touched, the gill and siphon withdrawal reflex lasted only about 1 second.

neuroscientists-transfer-memories-from-one-snail-to-another

Figure: Sea Hare Stimulus Protocol. Image credit: Alexis Bédécarrats, Shanping Chen, Kaycey Pearce, Diancai Cai, and David L. Glanzman, eNeuro 14 May 2018, 5 (3) ENEURO.0038-18.2018; doi:10.1523/ENEURO.0038-18.2018.

The researchers then applied the RNA extracts from both trained and untrained sea hares to sensory neurons grown in the lab. The RNA extracts from the trained sea hares caused the sensory neurons to display heightened activity. Conversely, the RNA extracts from the untrained sea hares had no effect on the activity of the cultured sensory neurons.

Finally, the researchers added compounds called methylase inhibitors to the RNA extracts before injecting them into untrained sea hares. These inhibitors blocked the memory transfer. This result indicates that epigenetic modifications of DNA mediated by RNA molecules play a role in forming engrams.

Based on these results, it appears that RNA mediates the formation and storage of memories. And, though the research team does not know which class of RNAs play a role in the formation of engrams, they suspect that micro RNAs may be the biochemical actors.

Biomedical Implications

Now that the UCLA researchers have identified RNA and epigenetic modifications of DNA as central to the formation of engrams, they believe that it might one day be possible to develop biomedical procedures that could treat memory loss that occurs with old age or with diseases such as Alzheimer’s and dementia. Toward this end, it is particularly encouraging that the researchers could transfer memories from one sea hare to another. This insight might even lead to therapies that would erase horrific memories.

Of course, this raises questions about human nature—specifically, the relationship between the brain and mind. For many people, the fact that there is a physical basis for memories suggests that our mind is indistinguishable from the activities taking place within our brains. To put it differently, many people would reject the idea that our mind is a nonphysical substance, based on the discovery of engrams.

Engrams, Brain, and Mind

However, I would contend that if we adopt the appropriate mind-body model, it is possible to preserve the concept of the mind as a nonphysical entity distinct from the brain even if engrams are a reality. A model I find helpful is based on a computer hardware/software analogy. Accordingly, the brain is the hardware that manifests the mind’s activity. Meanwhile, the mind is analogous to the software programming. According to this model, hardware structures—brain regions—support the expression of the mind, the software.

A computer system needs both the hardware and software to function properly. Without the hardware, the software is just a set of instructions. For those instructions to take effect, the software must be loaded into the hardware. It is interesting that data accessed by software is stored in the computer’s hardware. So, why wouldn’t the same be true for the human brain?

We need to be careful not to take this analogy too far. However, from my perspective, it illustrates how it is possible for memories to be engrams while preserving the mind as a nonphysical, distinct entity.

Designed for Discovery

The significance of this discovery extends beyond the mind-brain problem. It’s provocative that the biology of a creature such as the sea hare could provide such important insight into human biology.

This is possible only because of the universal nature of biological systems. All life on Earth shares the same biochemistry. All life is made up of the same type of cells. Animals possess similar anatomical and physiological systems.

Most biologists today view these shared features as evidence for an evolutionary history of life. Yet, as a creationist and an intelligent design proponent, I interpret the universal nature of the cell’s chemistry and shared features of biological systems as manifestations of archetypical designs that emanate from the Creator’s mind. To put it another way, I regard the shared features of biological systems as evidence for common design, not common descent.

This view leads to the follow-up rebuttal: Why would God create using the same template? Why not create each biochemical system from scratch to be ideally suited for its function? There may be several reasons why a Creator would design living systems around a common set of templates. In my estimation, one of the most significant reasons is discoverability. The shared features of biochemical and biological systems make it possible to apply what we learn by studying one organism to all others. Without life’s shared features, the discipline of biology wouldn’t exist.

This discoverability makes it easier to appreciate God’s glory and grandeur, as evinced by the elegance, sophistication, and ingenuity in biochemical and biological systems. Discoverability of biochemical systems also reflects God’s providence and care for humanity. If not for the shared features, it would be nearly impossible for us to learn enough about the living realm for our benefit. Where would biomedical science be without the ability to learn fundamental aspects of our biology by studying model organisms such as yeast, fruit flies, mice—and sea hares?

The shared features in the living realm are a manifestation of the Creator’s care and love for humanity. And there is nothing bizarre about that.

Resources

Endnotes

  1. Alexis Bédécarrats et al., “RNA from Trained Aplysia Can Induce an Epigenetic Engram for Long-Term Sensitization in Untrained Aplysia,” eNeuro 5 (May/June 2018): e0038-18.2018, 1–11, doi:10.1523/ENEURO.0038-18.2018.
  2. For example, see Germain U. Busto et al., “microRNAs That Promote Or Inhibit Memory Formation in Drosophila melanogaster,” Genetics 200 (June 1, 2015): 569–80, doi:10.1534/genetics.114.169623.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2018/09/26/neuroscientists-transfer-memories-from-one-snail-to-another-a-christian-perspective-on-engrams

The Multiplexed Design of Neurons

multiplexeddesignneurons

BY FAZALE RANA – AUGUST 22, 2018

In 1910, Major General George Owen Squier developed a technique to increase the efficiency of data transmission along telephone lines that is still used today in telecommunications and computer networks. This technique, called multiplexing, allows multiple signals to be combined and transmitted along a single cable, making it possible to share a scarce resource (available phone lines, in Squier’s day).

Today, there are a number of ways to carry out multiplexing. One of them is called time-division multiplexing. While other forms of multiplexing can be used for analog data, this technique can only be applied to digital data. Data is transmitted as a collection of bits along a single channel separated by a time interval that allows the data groups to be directed to the appropriate receiver.

Researchers from Duke University have discovered that neurons employ time-division multiplexing to transmit multiple electrical signals along a single axon.1 The remarkable similarity between data transmission techniques used by neurons and telecommunication systems and computer networks is provocative. It can also be marshaled to add support to the revitalized Watchmaker argument for God’s existence and role in the origin and design of life.

A brief primer on neurons will help us better appreciate the work of the Duke research team.

Neurons

The primary component of the nervous system (the brain, spinal cord, and the peripheral system of nerves), neurons are electrically excitable cells that rely on electrochemical processes to receive and send electrical signals. By connecting to each other through specialized structures called synapses, neurons form pathways that transmit information throughout the nervous system.

Neurons consist of the soma or cell body, along with several outward extending projections called dendrites and axons.

multiplexed-design-of-neuronsImage credit: Wikipedia

Dendrites are “tree-like” projections that extend from the soma into the synaptic space. Receptors on the surface of dendrites bind neurotransmitters deposited by adjacent neurons in the synapse. These binding events trigger an electrical signal that travels along the length of the dendrites to the soma. However, axons conduct electrical impulses away from the soma toward the synapse, where this signal triggers the release of neurotransmitters into the extracellular medium, initiating electrical activity in the dendrites of adjacent neurons.

Sensory Neurons

In the world around us, many things happen at the same time. And we need to be aware of all of these events. Sensory neurons react to stimuli, communicating information about the environment to our brains. Many different types of sensory neurons exist, making possible our sense of sight, smell, taste, hearing, touch, and temperature. These sensory neurons have to be broadly tuned and may have to respond to more than one environmental stimulus at the same time. An example of this scenario would be carrying on a conversation with a friend at an outdoor café while the sounds of the city surround us.

The Duke University researchers wanted to understand the mechanism neurons employ when they transmit information about two or more environmental stimuli at the same time. To accomplish this, the scientists trained two macaques (monkeys) to look in the direction of two distinct sounds produced at two different locations in the room. After achieving this step, the researchers planted electrodes into the inferior colliculus of the monkeys’ brains and used these electrodes to record the activity of single neurons as the monkeys responded to auditory stimuli. The researchers discovered that each sound produced a unique firing rate along single neurons and that when the two sounds were presented at the same time, the neuron transmitting the electrical signals alternated back and forth between the two firing rates. In other words, the neurons employed time-division multiplexing to transmit the two signals.

Neuron Multiplexing and the Case for Creation

The capacity of neurons to multiplex signals generated by environmental stimuli exemplifies the elegance and sophistication of biological designs. And it is discoveries such as these that compel me to believe that life must stem from the work of a Creator.

But the case for a Creator extends beyond the intuition of design. Discoveries like this one breathe new life into the Watchmaker argument.

British natural theologian William Paley (1743–1805) advanced this argument by pointing out that the characteristics of a watch—with the complex interaction of its precision parts for the purpose of telling time—implied the work of an intelligent designer. Paley asserted by analogy that just as a watch requires a watchmaker, so too, does life require a Creator, since organisms display a wide range of features characterized by the precise interplay of complex parts for specific purposes.

Over the centuries, skeptics have maligned this argument by claiming that biological systems only bear a superficial similarity to human designs. That is, the analogy between human designs and biological systems is weak and, therefore, undermines the conclusion that a Divine Watchmaker exits. But, as I discuss in The Cell’s Design, the discovery of molecular motors, biochemical watches, and DNA computers—biochemical complexes with machine-like characteristics—energizes the argument. These systems are identical to the highly sophisticated machines and devices we build as human designers. In fact, these biochemical systems have been directly incorporated into nanotechnologies. And, we recognize that motors and computers, not to mention watches, come from minds. So, why wouldn’t we conclude that these biochemical systems come from a mind, as well?

Analogies between human machines and biological systems are not confined to biochemical systems. We see them at the biological level as well, as the latest work by the research team from Duke University illustrates.

It is fascinating to me that as we learn more about living systems, whether at the molecular scale, the cellular level, or the systems stage, we discover more and more instances in which biological systems bear eerie similarities to human designs. This learning strengthens the Watchmaker argument and the case for a Creator.

Resources

Endnotes

  1. Valeria C. Caruso et al., “Single Neurons May Encode Simultaneous Stimuli by Switching between Activity Patterns,” Nature Communications 9 (2018): 2715, doi:10.1038/s41467-018-05121-8.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2018/08/22/the-multiplexed-design-of-neurons

Design Principles Explain Neuron Anatomy

designprinciples

BY FAZALE RANA – AUGUST 15, 2018

It’s one of the classic episodes of I Love Lucy. Originally aired on September 15, 1952, the episode entitled “Job Switching” finds Lucy and Ethel working at a candy factory. They have been assigned to an assembly line, where they are supposed to pick up pieces of candy from a moving conveyor belt, wrap them, and place the candy back on the assembly line. But the conveyor belt moves too fast for Lucy and Ethel to keep up. Eventually, they both start stuffing pieces of candy into their mouths, under their hats, and in their blouses, as fast as they can as pieces of candy on the assembly line quickly move beyond their reach—a scene of comedic brilliance.

This chaotic (albeit hilarious) scene is a good analogy for how neurons would transmit electrical signals throughout the nervous system if not for the clever design of the axons that project from the nerve cell’s soma, or cell body.

The principles that undergird the design of axons were recently discovered by a team of bioengineers at the University of California, San Diego (UCSD).1 Insights such as this highlight the elegant designs that characterize biological systems—designs worthy to be called the Creator’s handiwork—no joke.

Neurons

The primary component of the nervous system (the brain, spinal cord, and the peripheral system of nerves), neurons are electrically excitable cells, thanks to electrochemical processes that take place across their cell membranes. These electrochemical activities allow the cells to receive and send electrical signals. By connecting to each other through specialized structures called synapses, neurons form pathways that transmit information throughout the nervous system. Neurologists refer to these pathways as neural circuits.

The heart of a neuron is the soma or cell body. This portion of the cell harbors the nucleus. Two sets of projections emanate from the soma: dendrites and axons. Dendrites are “tree-like” projections that extend from the soma into the synaptic space. Receptors on the surface of dendrites bind neurotransmitters deposited by adjacent neurons in the synapse. These binding events trigger an electrical signal that travels along the length of the dendrites to the soma. On the other hand, axons conduct electrical impulses away from the soma toward the synapse where this signal triggers the release of neurotransmitters into the extracellular medium, initiating electrical activity in the dendrites of adjacent neurons. Many dendrites feed the soma, but the soma gives rise to only a single axon, though the axon can branch extensively for some types of nerve cells. Axons vary significantly in terms of their diameter and length. Their diameter ranges from 1 to 20 microns. Axons can be quite long, up to a meter in length.

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Image: A Neuron. Image source: Wikipedia

The electrical excitability of neurons stems from the charge separation across its cell or plasma membrane that arises due to concentration differences in positively charged sodium, potassium, and calcium ions between the cell’s interior and exterior surroundings. This charge difference sets up a voltage across the membrane that is maintained by the activity of proteins embedded within the membranes called ion pumps. This voltage is called the resting potential. When the neuron binds neurotransmitters, this event triggers membrane-bound proteins called ion channels to open up, allowing ions to flow across the membrane. This causes a localized change in the membrane voltage that propagates along the length of the dendrite or axon. This propagating voltage change is called an action potential. When the action potential reaches the end of the axon, it triggers the release of neurotransmitters into the synaptic space.

Why Are Neurons the Way They Are?

The UCSD researchers wanted to understand the principles that undergird the neuron design, specifically why the length and diameter of the axons varies so much. Previous studies indicate that axons aren’t structured to minimize the use of cellular material—otherwise they wouldn’t be so long and convoluted. Nor are they structured for speed because axons don’t propagate electrical signals as fast as they could, theoretically speaking.

Even though the UCSD bioengineers adhere to the evolutionary paradigm, they were convinced that design principles must exist that explain the anatomy and physiology of neurons. From my perspective, their conviction is uncharacteristic of many life scientists because of the nature of evolutionary mechanisms (unguided, historically contingent processes that co-opt and cobble together existing designs to create new biological systems). Based on these mechanisms, there need not be any rationale for why things are the way they are. In fact, many evolutionary biologists view most biological systems as flawed, imperfect systems that are little more than kludge jobs.

But their conviction paid off. They discovered an elegant rationale that explains the variation in axon lengths.

Refraction Ratio

The UCSD investigators reasoned that the cellular architecture of axons may reflect a trade-off between (1) the speed of signal transduction along the axon, and (2) the time it takes the axon to reset the resting potential after the action potential propagates along the length of the axon and to ready the cell for the next round of neurotransmitter release.

To test this idea, the research team defined a quantity they dubbed the refraction ratio. This is the ratio of the refractory period of a neuron and the time it takes the electrical signal to transmit along the length of the axon. These researchers calculated the refraction ratio for 12,000 axon branches of rat basket cells. (These are a special type of neuron with heavily branched axons.) They found the information they needed for these calculations in the NeuroMorpho database. They determined that the average value for the refraction ratio was 0.92. The ideal value for the refraction ratio is 1.0. A value of 1.0 for the refraction ratio reflects optimal efficiency. In other words, the refraction ratio appears to be nearly optimal.

If not for this optimization, then signal transmission along axons would suffer the same fate as the pieces of candy on the assembly line manned by Lucy and Ethel. Things would become a jumbled mess along the length of the axons and at the synaptic terminus. And, if this happened, the information transmitted by the neurons would be lost.

The researchers concluded that the axon diameter—and, more importantly, its length—are varied to ensure that the refraction ratio remains as close to 1.0 as possible. This design principle explains why the shape, length, and width of axons varies so much. The reset time (refractory period) cannot be substantially altered. But the axon geometry can be altered, and this variation controls the transmission time of the electrical signal along the axon. To put it another way, axon geometry is analogous to slowing down or speeding up the conveyor belt to ensure that the candy factory workers can wrap as many pieces of candy as possible, without having to eat any or tuck them under their hats.

The Importance of Axon Geometry

The researchers from UCSD think that the design principles they have uncovered may be helpful in understanding some neurological disorders. They reason that if a disease leads to changes in neuronal anatomy, the axon geometry may no longer be optimized (causing the refraction ratio to deviate from its ideal value). This deviation will lead to loss of information when nerve cells transmit electrical signals through neural circuits, potentially contributing to the etiology of neurological diseases.

This research team also thinks that their insights might have use in computer technology. Understanding the importance of refraction ratio should benefit the design of machine-learning systems based on brain-like neural networks. At this time, the design of machine-learning systems doesn’t account for the time it takes for signals to reach neural network nodes. By incorporating this temporal parameter into the design, the researchers believe that they can dramatically improve the power of neural networks. In fact, this research team is now building new types of machine-learning architectures based on these new insights.2

Axon Geometry and the Case for Creation

The elegant, optimized, sophisticated, and ingenious design displayed by axon geometry is the type of evidence that convinced me, as an agnostic graduate student studying biochemistry, that life must stem from the work of a Creator. The designs we observe in biology (and biochemistry) are precisely the types of designs that we would expect to see if a Creator was responsible for life’s origin, history, and design.

On the other hand, evolutionary mechanisms (based on unguided, directionless processes that rely on co-opting and modifying existing designs to create biological innovation) are expected to yield biological designs that are inherently limited and flawed. For many life scientists, the varying length and meandering, convoluted paths taken by axons serve as a reminder that evolution produces imperfect designs, just good enough for survival, but nothing more.

And, in spite of this impoverished view of biology, the UCSD bioengineers were convinced that there must be a design principle that explained the variable length of axons. And herein lies the dilemma faced by many life scientists. The paradigm they embrace demands that they view biological systems as flawed and imperfect. Yet, biological systems appear to be designed for a purpose. And, hence, biologists can’t stop from using design language when they describe the structure and function of these systems. Nor can they keep themselves from seeking design principles when they study the architecture and operation of these systems. In other words, many life scientists operate as if life was the product of a Creator’s handiwork, though they might vehemently deny God’s influence in shaping biology—and even go as far as denying God’s existence. In this particular case, the commitment these researchers had to a de facto design paradigm paid off handsomely for them—and scientific advance.

The Converse Watchmaker Argument

Along these lines, it is provocative that the insights the researchers gleaned regarding axon geometry and the refraction ratio may well translate into improved designs for neural networks and machine-learning systems. The idea that biological designs can inspire engineering and technology advances makes possible a new argument for God’s existence—one I have named the converse Watchmaker argument.

The argument goes something like this: if biological designs are the work of a Creator, then these systems should be so well-designed that they can serve as engineering models and otherwise inspire the development of new technologies.

At some level, I find the converse Watchmaker argument more compelling than the classical Watchmaker analogy. Again, it is remarkable to me that biological designs can inspire engineering efforts.

It is even more astounding to think that engineers would turn to biological designs to inspire their work if biological systems were truly generated by an unguided, historically contingent process, as evolutionary biologists claim.

Using biological designs to guide engineering efforts seems to be fundamentally incompatible with an evolutionary explanation for life’s origin and history. To think otherwise is only possible after taking a few swigs of “Vitameatavegamin” mix.

Resources

Endnotes

  1. Francesca Puppo, Vivek George, and Gabriel A. Silva, “An Optimized Structure-Function Design Principle Underlies Efficient Signaling Dynamics in Neurons,” Scientific Reports 8 (2018): 10460, doi:10.1038/s41598-018-28527-2.
  2. Katherine Connor, “Why Are Neuron Axons Long and Spindly? Study Shows They’re Optimizing Signaling Efficiency,” UC San Diego News Center, July 11, 2018, https://ucsdnews.ucsd.edu/pressrelease/why_are_neuron_axons_long_and_spindly.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2018/08/15/design-principles-explain-neuron-anatomy