Study Identifies First Brain Cells that Respond to Sound

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Study Identifies First Brain Cells that Respond to Sound

Post by Cr6 on Sat Dec 23, 2017 3:42 pm





Study Identifies First Brain Cells that Respond to Sound
Dec 21, 2017 by News Staff / Source


A new study by University of Maryland’s Professor Patrick Kanold and co-authors is the first to identify a mechanism that could explain an early link between sound input and cognitive function, often called the ‘Mozart effect.’ The results are published in the Proceedings of the National Academy of Sciences.

Working with young ferrets, Professor Kanold and colleagues observed sound-induced nerve impulses in subplate neurons, which help guide the formation of neural circuits in the same way that a scaffolding helps a construction crew erect a new building.

This is the first time such impulses have been seen in these neurons.

“Our work is the first to suggest that very early in brain development, sound becomes an important sense,” said co-author Dr. Amal Isaiah, also from the University of Maryland.

“It appears that the neurons that respond to sound play a role in the early functional organization of the cortex. This is new, and it is really exciting.”

During development, subplate neurons are among the first neurons to form in the cerebral cortex — the outer part of the mammalian brain that controls perception, memory and, in humans, higher functions such as language and abstract reasoning.

The role of subplate neurons is thought to be temporary. Once the brain’s permanent neural circuits form, most subplate neurons disappear.

Scientists assumed that subplate neurons had no role in transmitting sensory information, given their transient nature.

They had thought that mammalian brains transmit their first sensory signals in response to sound after the thalamus, a large relay center, fully connects to the cerebral cortex.

Studies from some mammals demonstrate that the connection of the thalamus and the cortex also coincides with the opening of the ear canals, which allows sounds to activate the inner ear. This timing provided support for the traditional model of when sound processing begins in the brain.

However, researchers had struggled to reconcile this conventional model with observations of sound-induced brain activity much earlier in the developmental process.

Until Professor Kanold’s team directly measured the response of subplate neurons to sound.

“Previous research documented brain activity in response to sound during early developmental phases, but it was hard to determine where in the brain these signals were coming from,” Professor Kanold said.

“Our study is the first to measure these signals in an important cell type in the brain, providing important new insights into early sensory development in mammals.”

http://www.sci-news.com/othersciences/neuroscience/subplate-neurons-sound-05555.html

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by Jared Magneson on Tue Dec 26, 2017 10:43 pm

Interesting stuff. Of course, physiology is a logical and necessary arena where the Charge Field will answer many questions, as we scale on up from the photon level in our research. I'm nowhere near being helpful on this topic yet, but it certainly interests me. Botany as well, but it occurs to me that if physics is full of so many holes, biology and physiology must be full of even more as an extension. Hopefully we can start filling in some of these holes now that we have a more solid foundational field to work with.

For example, I've always pondered the "electrical current" aspect of neurons as being highly suspicious. Sure, these impulses exist, but how? Considering that any and all major scientists in these fields didn't have the Charge Field or even know what electricity is, I think we can make headway in these areas, at least conceptually.

So the neuron itself is either generating the charge (recycling it in a certain direction) or redirecting charge from elsewhere. Are the dendrites "siphoning" local charge, feeding the neuron?

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by LongtimeAirman on Wed Dec 27, 2017 6:15 pm

.
I’ve always avoided the biological side of things, but I must say, the dendrites look like atoms, connected by main north/south axis charge channels, and secondary lesser carousal level charge flows between adjacent dendrites. Given recent discussion, it makes perfect sense that photon energy channeled between the dendrites may be detected as high velocity underwater sound.
.

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by Jared Magneson on Thu Dec 28, 2017 12:43 am

I agree that charge is definitely in play here, but the illustration in the article is just that, an illustration. It's actually pretty hard to find good photos of neurons, which is strange since they're larger than sperm cells allegedly.

Here's on that I think might be real:


Here's another, from the Wiki. Golgi-stained neurons from a human brain:



And another from the Wiki, showing what they call pyramidal structure:



It's difficult to say if they're polarized, though. They aren't spinning, that I'm aware of. But the do seem to exhibit similar behavior to charge channels.

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by Cr6 on Thu Dec 28, 2017 2:32 am

Always an interesting topic... chemistry and our "thinking" (charge field receiving/cycling/processing... AFAICT)

https://thequantifiedbody.net/oxaloacetate-anti-aging-alan-cash/

Interesting that the pathways for "fueling" the brain and body are connected directly with "health" generally.
AMPK and NADH/NAD+
http://quantifiedbody.podbean.com/mf/web/psz8rv/Quantified-Body-Podcast-Ep-30-oxaloacetate-anti-aging-with-Alan-Cash.mp3

A good paper:
BRAIN GLYCOGEN METABOLISM DURING HYPOGLYCEMIA: ROLE IN HYPOGLYCEMIA ASSOCIATED AUTONOMIC FAILURE, MEMORY, AND NEURONAL CELL DEATH
https://cardinalscholar.bsu.edu/bitstream/handle/123456789/194984/WeaverS_2011-3_BODY.pdf?sequence=1

https://en.wikiversity.org/wiki/Chemistry_and_consciousness/Is_consciousness_a_chemical_process%3F

Desperately seeking sugar: glial cells as hypoglycemia sensors.

http://europepmc.org/articles/PMC1297271/

Proposed glial-neuronal loop at work in central sensing of hypoglycemia via GLUT2, based on the study by Marty et al. in this issue (9). This scheme illustrates the pivotal role of GLUT2 in glial cells in first-hand detection of hypoglycemia. How these specific glial cells then connect to neurons within the brainstem (likely in the NTS and the dorsal motor nucleus of the vagus) to relay information is unknown but may involve the lactate shuttle as well as signaling via the Kir6.2 ATP-regulated K+ channel (not illustrated). The drop in glycemia may also be directly sensed by neurons and pancreatic α and β cells but not through GLUT2 (the transporter/detectors involved are so far unknown). Ultimately, autonomic nervous signals and the drop in intraislet insulin levels promote glucagon secretion.
http://europepmc.org/wicket/bookmarkable/uk.bl.ukpmc.web.utilities.redirect.RedirectPage?figure=F1/&articles=PMC1297271

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by Cr6 on Fri Dec 29, 2017 12:14 am

Sorry that last post came across a bit random.  Was drinking a bit yesterday when I posted it.

Just wanted to add this article from the linked paper. "Thinking" and memory is connected with the neurons and the glutamine/glutamate/glycogen cycles.  Apparently this cycle is pretty autonomous unless hypoglycemia occurs -- then memory and thinking rather quickly "fail" to occur. The charge field/chemical reactions must get glucose/glycogen/glutamine/glutamate to pulse the cycle again for thinking and recall to occur again.
-------
(Weaver paper page 16)
Glutamate synthesis and metabolism in the neuron and astrocyte In the neuron and astrocyte, glucose is metabolized through glycolysis to pyruvate. In the astrocyte, glycogen can also be metabolized to pyruvate. Pyruvate can then be metabolized anaerobically to generate lactate or aerobically to generate acetyl CoA using pyruvate dehydrogenase. Acetyl CoA then enters the TCA cycle condensing with oxaloacetate to make citrate. Citrate then goes through a variety of intermediates to generate ATP and regenerate oxaloacetate to ensure another turn of the TCA cycle. In the astrocyte, however, pyruvate can also be metabolized aerobically to generate a new molecule of oxaloacetate using pyruvate carboxylase. If pyruvate enters the TCA cycle as a new molecule of oxaloacetate, it can condense with acetyl CoA to make a new molecule of citrate. The new molecule of citrate can then generate α-ketoglutarate which can leave the TCA cycle to undergo transamination to form glutamate. Glutamate is then converted to glutamine using glutamine synthetase. The glutamine synthesized in the astrocyte is shuttled across the extracellular space to the neuron where it is converted to glutamate using phosphate activated glutaminase. Glutamate can then be released from the neuron as an excitatory neurotransmitter, metabolized to GABA, an inhibitory neurotransmitter, or undergo a transamination reaction to generate α-ketoglutarate which can be metabolized for energy in the TCA cycle. If glutamate is released from the neuron, it is taken back up by the astrocyte and converted to glutamine by glutamine synthetase or can undergo a transamination reaction to form α-ketoglutarate which can then be metabolized for energy in the TCA cycle. If the glutamate is turned into glutamine, the glutamine can once again be shuttled to the neuron. The shuttling of glutamate and glutamine is known as the glutamate/glutamine cycle.

Glycogen is proposed to be the major precursor to glutamate synthesis and, hence, is expected to be important for learning and memory consolidation. The importance of glycogen was shown using bead discrimination tests in day-old chicks treated with various inhibitors of glycogenolysis and glutamate uptake. Brain glycogen turnover increases during neuronal activation. However, when the breakdown of glycogen is inhibited, memory consolidation was dramatically reduced in the chick (18). When glycogen phosphorylase was inhibited, memory formation decreased in a dose dependent manner. When glutamate uptake was inhibited, memory loss was immediate (15). These findings suggest that glycogen may be the preferred precursor to glutamate in regards to learning and memory consolidation.

------------

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by Cr6 on Fri Dec 29, 2017 12:38 am

Related... sorry if this rambles:
--------

Francis Crick -- The Astonishing Hypothesis

The death of Francis Crick at the end of last month drew many eulogies, most of which naturally highlighted the discovery of the double helix structure of DNA. In the latter part of his life, however, Crick turned his attention to the problem of consciousness rather than genetics or microbiology. He seems to have been temperamentally inclined to working in collaboration with a partner - having cracked the mystery of DNA with Watson, he now developed a fruitful partnership with Christof Koch. His view of consciousness, however, was summed up in his own book 'The Astonishing Hypothesis'.

The hypothesis in question is '...that "You", your joys and your sorrows, your memories and your ambitions, your sense of personal identity and free will, are in fact no more than the behaviour of a vast assembly of nerve cells and their associated molecules.'

It has been suggested by some that this is not such an astonishing hypothesis after all. Certainly the idea that our mental life arises from the activity of the brain has been a mainstream one for a considerable time, but the key words in Crick's hypothesis are perhaps 'no more than'. On the face of it, this is indeed a fairly extreme claim; a reductionism which stops just short of denying the actual existence of consciousness. The quotation marks around the word 'You' suggest that Crick was also tempted by scepticism about the self.

It's difficult to be absolutely clear about Crick's philosophical position, however. Searle criticised 'The Astonishing Hypothesis' for not being clear about exactly what kind of reductionism it was putting forward, and with some justice: at times Crick talks in terms of emergence, and he seems to want to disavow naive or eliminativist reductionism, but his bottom line does seem to be that consciousness is nothing more than the activity of neurons.

One reason for this lack of clarity is perhaps that Crick, as he very fairly points out, is not even trying to set out a finished theory, only a hypothesis and a suggested line of attack. But the fundamental reason is that Crick is really interested in telling a scientific story, not a philosophical one. Most of the book is taken up with doing this. Crick's strategy is to approach consciousness via a consideration of the faculty of vision. He gives a very clear and interesting account of research in this area, with a well-judged balance of speculation and caution. Personally, however, I think the focus on vision dooms the enterprise from the start, at least as far as consciousness is concerned. The best one can hope to get by investigating vision alone is some insight into attention and sensory awareness; the central issues of consciousness are likely to remain untouched. Blind people are fully conscious, after all!

It's also true that Crick's close focus on neurons at the expense of philosophy seems to lead him into some dubious positions. He and Koch are particularly known for the view that consciousness arises when sets of neurons fire in a co-ordinated way, at frequencies around 40 Hertz. Crick suggests that synchronised firing of this kind might, in particular, be the neural correlate of visual awareness. To be really consistent with Crick's general attitude, the firing really needs to be visual awareness, not just correlated with it, but that is perhaps a nit-picking point: the more fundamental difficulty is that no explanation is ever offered as to why co-ordinated firing should give rise to conscious experience. Crick suggests that this kind of co-ordination might be the answer to the notorious binding problem, because it explains how neurons in different visual areas which respond to different qualities of the seen object (form colour, motion, etc) 'temporarily become active as a unit', but it seems that at best that might be part of the answer. A particularly difficult aspect of the problem is that different pieces of sensory data which relate to the same object don't arrive in one place in the brain at the same time, yet our conscious experience never seems to suffer from, as it were, faulty lip sync. It's hard to see how simultaneous patterns of firing could deal with the chronological problem.

At the end of the book, Crick offers a short and tentative postscript setting out an idea about free will. This is really an explanation for why people think they have free will - Crick is presumably a determinist. His idea is that there is an unconscious part of the brain which makes the plans for what we are going to do: these plans then pop into the conscious mind as if from nowhere, giving an impression of free will. The conscious mind may be able to guess the factors behind the plans, or it may get them wrong: either way, it feels there is some mystery about the process. Crick, drawing on some research by Damasio, goes so far as to suggest that this unconscious planning facility (the 'seat of the will') is probably located in or near the anterior cingulate sulcus.

Of course it is perfectly true that the processes which give rise to conscious thought are not themselves conscious (otherwise we should be caught in a vicious regress), but that does not imply that consciousness is not in the driving seat. Often when we make a complex decision or draw up an explicit plan, we weigh the factors and consider possible events consciously in our minds, and it seems very hard to believe that this kind of process, which surely bears a remarkable resemblance to decision-making, is not ultimately responsible for the plan or decision which is eventually arrived at. Indeed, I think most people believe that making decisions and plans, and allowing human beings to rise above the influence of their immediate current environment, is exactly what consciousness is for.

(more at link)
http://www.consciousentities.com/crick.htm

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by Cr6 on Fri Dec 29, 2017 1:13 am

Christof Koch who worked with Crick:
-----------

One of the institute’s projects involves taking bits of cortical tissue extracted during brain surgeries at Seattle hospitals, and running them through experiments while the brain cells are still fresh.

“This is not a mouse brain. This is a piece of living human brain,” Koch said. “Twenty minutes ago, it was part of somebody’s brain, with somebody’s memories of their first kids. But now it’s here, it’s in the lab, we can look at the morphology, we can study it in great detail.”

Koch said a database of human brain-cell reconstructions, including 3-D imagery, would be made freely available via the institute’s website later this month. As the database grows, researchers can use the reconstructions to model how electrical fields might affect brain function — or precisely what happens in the brains of patients with Alzheimer’s disease.

“This is going to be a long road ahead,” Koch acknowledged. But eventually, neuroscientists could gain enough of an understanding of the nervous system’s circuitry to restore lost functionality.

Researchers have already found ways to rewire paralyzed limbs so that they can respond to brain commands, and even provide sensory feedback, although the apparatus that’s been developed so far is typically too bulky for practical use.

Koch thinks it’s only a matter of time before brain-machine interfaces become small enough and capable enough to restore full function to a patient’s nervous system — and go even further.

“We are all interested in also enhancing all of our performance,” he said, “because I think this is one way we can continue to compete against our own creation. So this is the challenge for this century, really. The last century has been called the century of physics. This century is really the century of biology, and particularly brain science: trying to understand our brain, to cure diseases, but also to enhance our brain for our long-term survival.”

Koch isn’t alone in his view: Elon Musk, the billionaire CEO of SpaceX and Tesla, is also backing a venture called Neuralink that is focusing on developing powerful brain implants.

After his talk, Koch told GeekWire that he was on board with Musk’s vision for future brain chips.

“In general, that’s the right way to go,” Koch said. “The question is, how long is it going to take? Particularly, the regulatory hurdles are big. Anytime you drill a hole in somebody’s brain, you better have a very good reason for doing it, typically because the health is in danger.”

It can take a decade or two for surgical technology to make its way from the lab to the operating room, Koch pointed out. “If we want to attempt to make a difference in our lives, and not just in the lives of our children’s children, we have to do this faster,” he said.

Koch speculated that Musk just might be among the first people to get a brain chip purely for the purpose of mental enhancement rather than to restore lost neural function.

“All it takes is well-known people, maybe like Elon Musk, saying, ‘Yes, I’m going to put that chip into my brain. I’m going to get some surgeons, no matter when — and see? I can now do things that nobody else can do,'” Koch said. “Then, suddenly, you’ll see thousands of people everywhere who’ll want to do it.”

Love space and science? Sign up for our GeekWire Space & Science email newsletter for top headlines from Alan Boyle, GeekWire’s aerospace and science editor.

https://www.geekwire.com/2017/brain-scientist-christof-koch-merge-machine/

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by Cr6 on Fri Dec 29, 2017 1:20 am

Consciousness and Neuroscience
by
Francis Crick and Christof Koch
Cerebral Cortex     1998
Volume 8:97-107
----------------------------------------------------------------------------
http://virtual.sai.msu.su/~bond/crick-koch-cc-97.html



My comments on “Consciousness and Neuroscience”

Crick has done neurobiology a service by taking on the challenge of trying to find specific types of neuronal activity that are correlated with consciousness. This project has dramatic philosophical implications because so many philosophers have thought that issues like understanding consciousness are beyond the power of materialistic reductionistic science. “Consciousness and Neuroscience” is not much different after 8 years from “Towards a Neurobiological Theory of Consciousness” (1). This in itself could be taken as good evidence that most neurobiologists are correct when they think that it is premature for them to study consciousness. This sense of prematurity is amplified by the fact that there are only a few rare sources of data that Crick and Koch have so far found useful for analysis of the “neuronal correlate of consciousness”: 1) cases of human brain damage that alter consciousness, or results form lesioning studies in animals, 2) Non-invasive brain scanning methods like functional MRI and electrophysiological recordings from animals which are used in attempts to identify specific types of neurons with activity patterns that match the perceptual states of the animals. Some times these methods can be combined with method #1, and 3) electrical stimulation of specific brain regions that seem to be able to shift an animal’s conscious perception of a stimulus.
In the first part of this article, Crick and Koch summarize some recent results from these kinds of experiments.

When Crick took up the challenge of trying to identify a neuronal basis for consciousness, he must have thought that there was a real possibility that something relatively simple like 40 Hz feedback loops among thalamic and cortical brain regions would solve the problem. This was not a silly idea, as some philosophers have suggested, only overly optimistic. The most interesting parts of “Consciousness and Neuroscience” are the indications that Crick is now admitting that he will have to widen his search strategy and accept the fact that consciousness is a tougher problem to solve than the structure of DNA.

A main reason for the broadening of Crick’s analysis of consciousness is that simple tricks like the 40 Hz feedback signals have not solved the problem. Crick now accepts the idea that additional brain regions (such as prefrontal cortex) beyond the early visual sensory processing regions are important for even the most basic forms of visual sensory awareness, while the 40 Hz signals seem largely restricted to “lower” sensorymotor brain regions.

In a section called “Future Experiments” Crick and Koch issue a call for additional experimental techniques that could aid in the search for neural correlates of consciousness. It has recently become possible to reversibly inactivate specific populations of neurons using genetic engineering tricks. It should be possible to extend these methods to the primates used for consciousness research. Crick and Koch also point out that recent understanding about the molecular controls of the patterns of connectivity between neuron populations should lead to methods for specifically eliminating types of brain connections. This is a good idea, but it is interesting that “virtual elimination” of connection pathways is easy in computer models of the brain, and is one of the powerful tools available to people who work with computer models of the brain. Crick has never shown much interest in computer models of the brain, probably because he has hoped that solving problems like consciousness will be simple enough that we will not need to use computers as tools for aiding our understanding of how brains work. I suspect that he is overly optimistic about how easy it will be to understand things like consciousness in neurobiological terms.

Crick and Koch have provided a few short sections where they mention philosophy of mind. A section called, “Why are we conscious” deals with the idea of “zombies”. In a section called “Philosophical matters” they deal with qualia and “The problem of meaning”. Their general attitude towards philosophy of mind is reflected in the statement, “In recent years the amount of discussion about consciousness [by philosophers] has reached absurd proportions compared to the amount of relevant experimentation.” However, it is interesting that they thank Chalmers and Searle for helpful comments concerning this article. As a biologist, I am fairly comfortable with what Crick and Koch have to say about zombies and qualia, but I doubt that it is very satisfying for many philosophers.

In the section called, “The on-line system” Crick and Koch say, “It is obviously important to discover the difference between the on-line system [of vision, as can be shown to operate in people with blind-sight], which is unconscious, from the seeing system, which is conscious.” Contrast this with what they say near the end in discussing what will happen once neurobiologists have found a neuronal explanation for consciousness, “It is likely that scientists will then stop using the term consciousness except in a very loose way.” They compare this to the disinterest of biologists in debating the question of whether viruses are alive or dead. This is a very weak analogy by which the fact that viruses are in the fuzzy gray region between alive and dead is taken to imply that the word “alive” is not really of much use to biologists and that the word “consciousness” is similar in this regard. This is very misleading and misses to point entirely. The word “alive” is not usually found within the literature of biology because most of the time the distinction between what is alive and what is not alive is clear to everyone. We would no more expect to see an economist pausing frequently to point out to his audience what elements of an economic system are money, he and his readers all know this. What elements of ecosystems are alive, what elements of economies are money, and which aspects of brain activity are the neural correlates of consciousness are all issues of fundamental importance.

What I find most interesting in this paper is that Crick and Koch show signs of moving in the direction that Gerald Edelman proposed for consciousness research 10 years ago. One key aspect of Edelman’s theory of consciousness was that he proposed that consciousness is a global brain function, meaning that many widely distributed parts of the brain are important for consciousness. As mentioned above, 10 years ago Crick and Koch were pursuing the idea that a mechanism for a simple form of consciousness, visual awareness, might be found with just a few brain regions, the closely linked thalamic and visual cortex regions. Thus, it is remarkable to find Figure 1 in this article showing whole series of sensory and motor regions and even the environment. This is the kind of diagram which is found throughout Gerald Edelman’s work. The point that Crick makes with Figure 1 is that there are many possible control systems in a brain for taking sensory input and producing adaptive behavioral responses based on the sensory input. These systems seem to exist in a hierarchy from very quick and unconscious to conscious systems that, while slower, can be more refined. What is the basis of this “refinement” in behavior that is made possible by consciousness? Crick and Koch are reluctant to say the words, but the key is learning and memory. The brain contains several memory systems which allow animals to combine current sensory inputs with past experience to produce adaptive behavior that makes sense for the animal in terms of the environment that the animal exists in.

Why are Crick and Koch so reluctant to admit that the problems of learning and memory are fundamentally involved in consciousness? Basically, because learning and memory are the real “hard problem” of mind. Crick has hoped that there is some simple trick that brains use to produce consciousness that can be found without us first having to understand learning and memory. However, I think Crick is wrong. I favor Gerald Edelman’s approach to consciousness which places memory squarely at the center of the problem of consciousness.

This fundamental issue (the relevance of memory mechanisms and learning in our attempt to understand consciousness) is most directly (and it is not very direct at all) confronted in the section called “The problem of meaning.” I agree with the idea that the problem of meaning has two aspects: 1) how is meaning expressed in neural terms?, and 2) how does the expression of meaning arise? These are the two issues at the heart of Gerald Edelman’s theory of consciousness. The answers to these questions are simply 1) memory and 2) learning. Importantly, Edelman’s approach is to tackle the two together, since memories are the result of learning. I think Crick is admitting (very quietly) that the unconscious-consciousness hierarchy (see Figure 1 of "Consciousness and Neuroscience") is defined by the memory mechanisms that are involved in each level of the hierarchy. Crick is admitting that understanding the neuronal correlate of consciousness would be a sterile result in itself because what is really important to consciousness is meaning. A person can be conscious of sensory inputs, but if those experienced inputs have no meaning for a person, then no sensible behavior will result, you would have a zombie that has low-level awareness, but nothing more. It is hard to see the distinction between such a meaningless conscious existence and unconsciousness. The distinction between consciousness and unconsciousness depends on the meaningfulness of conscious experiences and memory is the source of meaning. Edelman saw this all clearly, and I think, in the end, Crick will have to admit openly that Edelman was correct. This is hard for Crick to do because 10 years ago he issued a scathing attack on Edelman’s theory of mind and Crick went off in a different direction. It is at least promising to see Crick finally starting to open the door towards his acceptance of the importance of memory and learning in our attempt to understand consciousness. I see the same glimmer of hope in Rey’s CRTT, in which he admits that there must be a mechanism for getting meaning (semantic content) into his LOT. Memory and learning are tough problems for neurobiologists, but progress is being made. It is not too much to hope that the neurobiology of learning and memory will soon begin to allow us to start to understand consciousness. Edelman was the first to show how this can work in theory, only the details of the explanation remain to be filled in.   Back to first Crick page.

1. Francis Crick and Christof Kock "Towards a Neurobiological Theory of Consciousness" (1990) Seminars in the Neurosciences, 2: 263-275.


https://web.archive.org/web/19991012163508/www.geocities.com/ResearchTriangle/System/8870/books/crick2.html

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Re: Study Identifies First Brain Cells that Respond to Sound

Post by Cr6 on Fri Dec 29, 2017 2:32 am

What dopamine does in the brain
http://www.pnas.org/content/108/47/18869.full

(a pretty good article on neurotransmitters... note the dependency on "ion channels" for proper "thinking".)


The biosynthesis of acetylcholine, serotonin, norepinephrine, and GABA had been elucidated, and their degradative pathways had been established. Their release by exocytosis was generally accepted. Synaptic inactivation by an enzyme in the case of acetylcholine and for amines and amino acids, by reuptake into the nerve endings that had released them seemed on solid ground. However, molecular characterization of the most important element of synaptic transmission, transmitter receptors, was still unattained, at least in the brain.

It was generally assumed that neurotransmitters bound to receptor proteins on postsynaptic membranes. Several investigators had identified the receptor protein for the actions of acetylcholine in the electric organ of the electric eel through the binding of radiolabeled α-bungarotoxin (3). However, the receptor in these electric organs comprises 20% of membrane protein, about 1 million times as dense as what would be expected in the brain. Thus, few investigators anticipated ever understanding neurotransmitter receptors in the brain at a biochemical level, and the identification by ligand binding of neurotransmitter and drug receptors in the mid-1970s came as a surprise (4).

For neurotransmitters that act by opening ion channels, such as acetylcholine at the neuromuscular junction, transmitter recognition was presumed to be transformed into an opening or closing of ion channels. For the biogenic amines, such as norepinephrine and serotonin, the picture was murkier. Hence, the work of Kebabian and Greengard (5) and Kebabian et al. (6) (Fig. 1) implying that dopamine in the superior cervical ganglion and the brain's caudate nucleus acts through a receptor coupled to a cAMP-forming enzyme—adenylate cyclase—was a giant step forward.

----

Abstract

The effect of the putative amino acid transmitter, L-glutamate, on adenylate cyclase in crude membrane preparations of the rat tapeworm Hymenolepis diminuta was investigated to determine if glutamate effects the generation of the second messenger cAMP. Addition of glutamate at 10−3 and 5.5 × 10−9 M resulted in significant elevations in basal activity of adenylate cyclase, while concentrations in the 10−5–10−7 M range caused significant depressions below basal activity. Assays with glutamate agonists and other acidic compounds showed glutamate to be the only amino acid, dicarboxylic acid, or acidic compound capable of this pattern of stimulation and inhibition. While the response of adenylate cyclase to glutamate agonists suggested that an N-methyl-D-aspartic acid (NMDA) type receptor may be present, glutamate agents acting as NMDA antagonists in vertebrate systems were agonists. Metabolic end products of glycolysis stimulated adenylate cyclase, suggesting that these, along with metabolic glutamate may regulate glycolytic enzymes. Only 10−3 M L-glutamate significantly stimulated adenylate cyclase activity in tissue slices, and this response was restricted to those slices rich in nervous tissues. L-Glutamate eliminated the 5-hydroxytryptamine (5-HT) stimulated adenylate cyclase response suggesting that glutamate can modulate the 5-HT stimulated elevations in adenylate cyclase activity. The data support the hypothesis that L-glutamate is a neurotransmitter–modulator in the cestode.

http://www.nrcresearchpress.com/doi/abs/10.1139/y91-005?journalCode=cjpp

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