"Opaque tangle of spaghetti"

http://www.thehindu.com/opinion/op-ed/neuroscientist-karl-deisseroth-on-how-we-see-and-control-brain/article8116854.ece?homepage=true

The "tangle of spaghetti", as neuroscientist Karl Deisseroth describes
the wiring of the brain, has posed a singular challenge to researchers:
how do you navigate an opaque mesh of 80 billion neurons to decipher
brain activity — emotions, memory and learning — or identify diseased
circuitry that manifests as autism or schizophrenia?

Now, two path-breaking techniques devised by Prof. Deisseroth and his
colleagues at Stanford University are changing the way we see,
understand and control the brain. The first technique "illuminates" the
brain, enabling researchers to manipulate electrical activity. In a
process called "optogenetics", specific targetted cells are infused with
a gene that directs the production of a light-sensitive protein (derived
from algae or other microbes) that can then turn brain cells on or off
in response to a focussed light signal.

The second is a "transparent brain" engineered through a method called
"CLARITY". This process makes brains transparent, by building a hydrogel
inside the brain, removing lipids that make the brain opaque. This
allows scientists to study the wiring of a three-dimensional brain in
its entirety, without having to laboriously dissect and reassemble
tissues as has been the practice.

Prof. Deisseroth, who is D.H. Chen Professor of Bioengineering and of
Psychiatry and Behavioural Sciences at Stanford University, was recently
awarded the prestigious Life Sciences Breakthrough Prize for 2016. He
spoke to Divya Gandhi in Bengaluru, where he begins a three-city lecture
tour as part of the Sixth Annual Cell Press-TNQ India Distinguished
Lectureship Series. Excerpts:

Laboratories around the world have begun using optogenetics to study and
manipulate the brain. Are there specific disorders that the technique
has proven particularly useful in shedding light on?

One of the most exciting things for me about this whole field is that I
get to see corresponding principles with my own clinical practice. In
the clinic, I see patients with treatment-resistant depression and also
those with autism spectrum disorders. And these are really challenging
and complicated clinically but they have certain symptoms — symptoms you
can study in animals. And another big example is anxiety. Anxiety is a
prominent feature of depression and is also a major problem in autism
spectrum disorders. We can study anxiety in a very reliable way in mice.
And that's been probably one of the biggest success stories.
Optogenetics is sorting out how anxiety works in the brain, what are the
pathways and cells that cause it or control it, and how it is all put
together. Anxiety is complicated. We know there are lots of parts to
anxiety. There is the heart rate change and the breathing rate change
and there is the avoidance aspects. Optogenetics has helped sort out how
all those parts are assembled.

Not least because of the lack of academic opportunity, doctors in India
tend not to go in for a PhD, something that critically undermines
cutting-edge research. As a clinical psychiatrist and a neuroscientist
doing front-end research, what would you recommend to encourage more
physician-researchers in India?

One thing that makes it work well in the U.S. is the existence of a very
well-defined MD-PhD training programme that is supported by the
government. It really helps to attract some of the best people to the
programme because you get support through medical school and through
graduate school from the federal government. The other thing is, at a
later career stage, making sure there are employment opportunities,
where one only practices in a clinic one or two days in a week, because
to really make competitive advances in research you need to spend most
of your time doing research.

How did you go about creating a see-through brain? And have there been
any significant, or unexpected, discoveries through CLARITY?

Around 2009, optogenetics was working really well in controlling neurons
with light. But we noticed that we couldn't quite make the final
intellectual step in understanding how the wiring of the brain causes
behaviour. With optogenetics, it is like roughly knowing where the parts
are in a computer but not knowing the detailed circuit diagram.

The central nervous system is the hardest thing to make transparent and
the reason is that the nervous system uses electricity to communicate
and it has to create insulated wires to send all that electricity
around, and the way the brain makes insulation is through lipids or fats
and those scatter photons. So it is almost impossible to make a living
transparent brain. You can slice it up into several thin sections and
try to reconstruct, which is the standard way of doing it. But that's
difficult and takes a long time. So we thought: how could we keep the
brain intact and make it transparent? So we had to remove the things
that are making it opaque — the lipids and fat. But that would normally
be destructive and cause the whole thing to dissolve, so we had to build
a new kind of support for the brain while we removed the fat. We
developed a chemical engineering trick by basically building a gel
within the brain that gives it the support it needs when we remove the
lipids and see through the brain.

The new insights have been pretty exciting actually. CLARITY has been
developing faster than optogenetics. But even in just the last year,
labs around the world are using CLARITY to make new discoveries. We have
been surprised to see certain patterns of wiring and connections across
the brain that we didn't know were there. It has also been used in human
brain tissue — Alzheimer's brains for instance — and seen some
interesting patterns.

In India, a country of over a billion people, we have, according to
guesstimates, just between 3,000 to 8,000 psychiatrists. Is that a
worrisome statistic, and is there an ideal ratio?

The best thing under these circumstances would be figuring out how to
train general practitioners to at least recognise the disorders and know
enough about the medications to provide. Of course, psychiatrists are
best because they have spent the most time thinking and learning the
about the ins and outs — but this may be the best short-term solution.

In 2010 you wrote about the stigma that surrounds psychiatric disease,
"just as a cancer diagnosis once carried more stigma than it does now."
Would you say there is a growing awareness about mental illness now and,
by extension, less prejudice around it?

I think that is happening. There is detectably, in the U.S., a more open
discussion and less stigmatisation of psychiatric disease but it is not
yet where it needs to be. A couple of things seem to help with reducing
prejudice and stigma. If people really understand how something works,
then they tend not to assign prejudicial or superstitious explanations.
The general public in the U.S. is getting a deeper knowledge and
understanding of psychiatry as biological. There has also have been
individual people writing books and speaking out and sharing their
experience with psychosis, depression or drug abuse. People aren't
hiding, they are coming out, saying "this is me".

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Japan, Hinduism, heritage, history

http://timesofindia.indiatimes.com/india/Hindu-gods-forgotten-in-India-revered-in-Japan/articleshow/50525067.cms

KOLKATA: Did you know that at least 20 Hindu deities are regularly
worshipped in Japan? In fact, there are hundreds of shrines to Goddess
Saraswati alone in that country, along with innumerable representations
of Lakshmi, Indra, Brahma, Ganesha, Garuda and others.

Even deities forgotten in India are worshipped in Japan. A unique
exhibition at Indian Museum here is set to throw light on the country's
long lost history that survives in a foreign land.

The Japan Foundation and filmmaker and art-historian Benoy K Behl have
collaborated to hold an exhibition of rare photographs that will be
inaugurated on Monday and will continue until January 21.

"The exhibition will be a rare treat for the eyes and the mind," said
Indian Museum education officer Sayan Bhattacharya.

The research that accompanies Behl's photographs reveals startling facts
about the importance of Indian heritage in Japan.

For instance, the 6th century Siddham script is preserved in Japan,
though it has disappeared from India. 'Beejaksharas' (or etymology of
alphabets) of Sanskrit in this script are regarded as holy and given
great importance. Each deity has a 'Beejakshara' and these are venerated
by the people, even though most of them cannot read it. Some Japanese
tombs are adorned with the Sanskrit alphabet.

At Koyasan, they still have a school where Sanskrit is taught in
Siddham, Behl's research revealed.
A number of words in the Japanese language have their roots in Sanskrit.
In Japanese supermarkets, a major brand of milk products is called
'Sujata'. The company's personnel are taught the story of Sujata who
gave sweet rice-milk to the Buddha, with which he broke his period of
austerity, before he achieved enlightenment. "All this and more are
revealed through Behl's photography," Bhattacharya added.


Apart from the language, there are deeper civilizational connections
that can be traced to early developments of philosophy in India, he
said.

Behl wrote in his research, "In many ways, this philosophic
understanding is most well preserved in Japan. Japan has not had the
breakdown of cultural norms which India suffered when a colonial
education system was created. Therefore, most Indians learnt about our
own culture from the Western point of view. The dominant and admired
language was English, which it remains till today."


The National Geographic had carried an 18-page story on ancient Indian
art revealed through Behl's photography to the world. The exhibition
will also explain how India's relationship with Japan.


"The deep-rooted spirit of the Buddha's teachings energizes the Japanese
people. Buddhist temples are numerous and vast numbers of people visit
these every day. Besides the Buddha, many ancient Indian deities and
practices (prevail) in their temples. An Indian feels quite at home in
Japan," Behl wrote.

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