Neural Networking, Alzheimer's Disease and Memory Share a Few Things

The hippocampi, as has already been discussed, are endowed with the task of binding elements of memory into a coherent trace. There are extensive interconnections within the hippocampi in the form of a local area network (LAN) or intranet. This LAN like architecture resembles the “Hopfield Network” of artificial neural networks. It is especially abundant in the CA3 neurones of the hippocampi. CA stands for Cornu Ammonis; meaning the horn of Ammon (After the ancient Egyptian God Amun).

In a Hopfield network, neurodes (neuronal equivalent of neurons) are connected to each other in the form of a bidirectional interconnection. However, a Hopfield network assumes that each neurode can have either of the two states: on (1) or off (0). But human neurons, we know, can also have additional states when it is in the summation or subtraction mode (spatial summation, temporal summation etc, whereby one neuron is incapable of eliciting a binary 1 or no action potential; but when suitably combined in a time [temporal scale] or a space scale [spatial], it can ). Reverberatory Hopfield networks reinforce each other, thereby strengthening the associations among themselves.

Earlier, mathematician cum scientist von Neumann tried to find an analogy between the memory architecture of a computer with that of a human brain. In a von Neumann architecture based computer, data can be fetched from their ‘address locations’ within the database when queried. Retrieval of data in a von Neumann model is sequential, that is the information flow is one by one. Human brain, on the other hand, handles data parallely, and there is no ‘bottleneck’ (which is inherent in the von Neumann model due to different locations of CPU and memory). No bottleneck means higher data transfer rate in the human brain. Human brains differ in another aspect. Secondly, human brain can think in terms of abstract terms, while a fixed program computer like von Neumann’s one, can not do so easily. In fact, human brain is far too superior in ‘fuzzy logic’ or abstract thinking compared to their silicon cousins.

The reverberatory circuit in the hippocampi is continuously synchronized with each input stimulus. This is akin to the synchronization of our circadian rhythms with that of daylight, via the retino-hypothalamic tract. The hippocampal anatomic correlate is somewhat like this: entorhinal cortex---> dentate gyrus---> CA1 & CA3 pyramidal neurons---> subiculum--> back to entorrhinal cortex. This circuit is heavily damaged in Alzheimer’s dementia resulting in loss of episodic memories and preventing acquisition of new memories. In artificial neural network model simulations, Traub and colleagues showed that the synchronization was done in the gamma frequency range. They showed that with the arrival of each theta cycle, the attractor-based autoassociative memory process got stronger and the attractor got stable after a few theta cycles. An attractor is somewhat like a binder, which indexes and binds information.

The hippocampi also get input from the basal ganglia and other portions of the brain. These regions have a diverse range of neurotransmitter chemicals. They include acetyl choline, GABA, NMDA, Dopamine, AMPA and many others.

In acetyl choline deprived state, as occurs in Alzheimer’s disease, the frequency of gamma  discharge diminished, leading to diminution of theta frequency thus delaying learning (and promoting unlearning or unbinding too).

Its time to disentangle the intracytoplasmic neurofibrillary tangles; and clear the mystery of the amyloid plaques which are so characteristic of AD. The stage, it seems, has been set. 

Last modified: May 1, 2013
[Picture courtesy: http://wikis.lib.ncsu.edu/]

Reference: Attractor neural network models of spatial maps in hippocampus

Misha Tsodyks

Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel 

E . Menschik (2003). Neuromodulatory control of hippocampal function: towards a model of Alzheimer''s disease . Artificial Intelligence in Medicine, Volume 13, 99-121

Crazy Little Thing Called Life

Scientists have recently discovered a body of evidence regarding the existence of water on the red planet and has, for obvious reasons, gone gaga over it. They are conjuring up all the possibilities of existence of life on it.

Well, what are the basic ingredients of life? Are carbon, hydrogen, nitrogen and similar molecules extremely essential (mandatory) for life? What constitutes life and above all, how is life defined? If prions, (which are nothing but misfolded proteins, the cause of a myriad of illnesses like mad cow disease, kuru, scrapie and various other diseases) can be counted as living organisms, then perhaps any complex molecule or even radioactive elements like Polonium 210, which disintegrates on its own, to form many other elements, which in turn disintegrates (reminds me of Iron Maiden's 'Seventh son of a Seventh son' song), may be said to have life too, for they undergo an automatic activity. If you pore into the inside of an atom, you can see interactions in the nucleus: mesons; orbiting electrons around them, dutifully obeying Pauli's principle and many such activities that mimic life. Or are they living things themselves?

( En passant: Polonium 210 is found in tobacco in minute quantities; it was used to poison the famous Russian political dissident Alexander Litvinenko).

Life on earth perhaps needed the carbon skeleton, or it may even have been due to a chance occurrence. Microorganisms have been discovered in conditions in places, hitherto considered inviable for life (Bacillus stearothermophilus, B subtilis, Thermus aquaticus for example). The constituent of life could be molecules other than the conventional ones, even anti-matter! If we zoom in, we find tissues, cells, microtubules, mitrochondria, nucleus, the DNA and various other things which themselves are teeming with life. Zooming further still, we enter the constituent molecules to find the hadrons and the leptons, deeper still, quarks and gluons etc etc. They all seem full of life to me.

Look at the celestial objects. The sun is said to be a middle-aged star. So? Heavenly objects sometimes die a violent death: in supernova, or turn into neutron stars or black holes or some 'dwarf's. And the universe is said to have been born in the form of a major birth pang called the Big Bang. Are they living things then?

We know that there is a very small probability of finding two exactly similar humans, having all identical attributes. Likewise, no two electrons orbiting the nucleus can have the same quantum state, as per Pauli's exclusion principle (teleportation using entanglement/twiddling is an exception, for here two particles at a distance have the same properties) . This only shows that like unique human minds, the not-so-living things can also have their own uniqueness. Can they be said to have a life too, for they too move, have mass and energy. What about a cellphone or a computer or anything having AI(Artificial intelligence).

Let's be introspective. You are as much life as I am and we are made up of molecules arranged in a particular configuration: just matter; but where is the life? It may be here, in the entity called consciousness. Consciousness may be explained in terms of interactions among material elements. When we are dead, what exactly is missing? We may be brain dead, but the transplant surgeon may take out the kidney or cornea to transplant on others. Thus even after we die, we still continue to live in some of our tissues: they remain alive!

The question of life has to be addressed holistically, if we want to arrive at a sane and unanimous conclusion. Till then controversy will rage.