Researchers at the University of Pittsburgh discovered that obesity directly affects the size of one’s brain. This as a result, affects one’s cognitive abilities. In other words, a fit individual has superior mental capabilities as compared to an overweight person.

Loss of Brain Tissue

They found that obese people have 8% less brain tissue than people of normal weight. Overweight people have 4% less brain tissue than people of normal weight. Obesity is classified as having a BMI (Body Mass Index) of 30 and above. Someone is overweight if their BMI falls within 25 and 30.

The researchers scanned the brains of 94 elderly people.  Although the test participants were elderly, they were all  cognitively normal. They were not afflicted by brain degenerating diseases such as Alzheimer or Parkinsons. According to Dr. Paul Thompson, a UCLA professor of neurology, just a 4% loss represents, “severe” brain degeneration.

The researches also informed that the brain tissue was lost in key areas that included;

• Frontal and temporal lobes: Critical for planning and memory
• Hippocampus: Important for long-term memory
• Anterior cingulate gyrus: Responsible for executive functions and attention
• Basal ganglia: Essential for proper movement and coordination

While this study was conducted on elderly people, other earlier studies had found similar correlations for younger participants.

Other Studies

In another study published in Obesity, researchers found that higher BMI correlated with reduced brain grey matter volume in the medial temporal lobes, hippocampus and precuneus. The average age of the 690 male participants was 42.

In a study published in Neuroimage, researchers found that participants with higher BMI had reduced grey matter volumes in the frontal operculum, postcentral gyrus and putamen. The  study identified structural brain differences in obese participants  in several brain areas involved in the regulation of taste, reward, and behavioral control. The outcome of this study seems to indicate that obesity is a downward spiral. The more obese one becomes, the more one looses control over the brain area that regulates behaviour and reward. The loss of control in these areas could be the reason why some overweight people have absolutely no control over their eating habits.

Reasons for Loss of Brain Matter

Research has also found some possible reasons for the degeneration of brain tissue with increasing body fat levels. One possibility could be raised levels of cortisol that is evident in overweight individuals. A study published in Neuroscience established the correlation between elevated levels of the cortisol hormone and brain degeneration.

Another reason for brain degeneration in overweight people could be due to the lack of exercise. The lack of exercise could be the reason that one is overweight in the first place. Exercise has been shown to preserve brain mass via the release of chemicals that regenerate neurons. Colcombe published a study which found that aerobic fitness reduced brain tissue loss.

Overweight people also generally have higher levels of the insulin hormone. Insulin is a potent fat storage hormone. An overweight person may or may not be diabetic. The insulin hormone can stay elevated for long periods before medical tests show the sign of diabetes. The chronic elevation of insulin levels is detrimental to the body and the brain. A study published in Neuroepidemiology stated the degenerative effects of excess insulin on cognitive functions and brain volume.

The evidence is mounting that being overweight leads to an absolutely poor quality of life. Not only does it lead to lifestyle diseases, but also to reduction of cognitive abilities. The best thing that one can do for his or her health is to maintain high levels of fitness.

Pictures courtesy of Danilo Rizzuti / FreeDigitalPhotos.net

]]> http://shadybrook.wordpress.com/2009/11/10/gps-london-cabbies-and-brain-swelling/ Wed, 11 Nov 2009 03:20:58 +0000 shadybrook http://shadybrook.wordpress.com/2009/11/10/gps-london-cabbies-and-brain-swelling/

Are GPS navigational devices damaging our sense of direction?

http://www.theweek.com/article/index/102501/The_last_word_This_is_your_brain_on_GPS

London cabbies must take a test called “The Knowledge” which requires them to memorize 25,000 streets and thousands of landmarks.  Here is a link to the Knowledge; http://www.the-knowledge.org.uk/main/

Apparently, the back part of the hippocampus in the brains of cabbies is enlarged compared with brains of the average person.    However, the front part of the hippocampus shrinks.

Every day, new brain cells (neurons) are born in the brains of adult mammals, a process called neurogenesis (neuro = neurons, genesis = birth).  These newborn cells appear particularly in the hippocampus – a brain area that is important for new memory formation.   Over the next few weeks, many of these newborn cells die off again.  But studies show that, if a rat has been exercising or has been exposed to new learning, more of the newborn cells survive.  The rate of survival of these new cells also depends on sleep.

As we sleep, we (like rats) cycle through several “stages,” including rapid-eye movement (REM) sleep, which is believed to be when we dream, and several kinds of non-REM sleep.

A recent study has suggested that REM is particularly important for neurogenesis in the hippocampus.  One group of rats were given four days of REM deprivation, by putting the rats in a small chamber where the floor was a treadmill that automatically activated whenever the rats entered REM sleep – forcing them to step forward to avoid being carried into the wall of the chamber.  (Non-REM sleep didn’t activate the treadmill.) For comparison, a group of control rats were placed in the same type of chamber, but treadmill activation was unrelated to sleep cycle.

The REM-deprived rats showed much less neurogenesis than controls. Both groups showed similar amounts of total sleep, and similar levels of stress hormones, indicating that the stress of being periodically awoken was similar for the REM-deprived and control rats. This study therefore suggests that REM sleep is particularly important for the birth and survival of new neurons in the adult brain.

There are two important implications of this study.  The first is that it adds to a growing literature suggesting that relatively short-term periods of sleep deprivation (equivalent to a few nights’ insomnia or intentional wakefulness) can significantly affect the brain.  This is a cautionary finding for those of us who routinely don’t get a full night’s sleep.

The second implication is that not all sleep is equal.  This study also adds to a growing literature suggesting that REM sleep has some special functions, particularly contributing to learning and memory.  Many medications, including some over-the-counter sleeping aids, disrupt REM sleep.  If REM sleep is indeed important for neurogenesis, then disrupting REM may disrupt neurogenesis – which might in turn have consequences for a person’s learning and memory abilities.

Further Reading:

R. Guzman-Marin et al. (2008). Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat. Sleep, 31(2):167-175.

I would love to see the Heenes have a reality show. True they exploited their kids in a ridiculous plot that had the world, me included, praying the kid would be okay but if you go to any child beauty pageant or talent agency you’ll see some real scary parents. I’m just saying, I would change my schedule around if the Heenes had a show. And most likely buy seasonal DVD’s. If Mike Vick can come back for doing the unthinkable, I believe we have it in our hearts to forgive the Heenes and watch their insanity from the safety of our couch. I mean, the kid’s name is Falcon and he blew chunks on national TV. This is gold people! And if Mr. Heene would say “one point twenty one gigawatts!” I would be a loyal fan for life.

Jon and Kate Gosselin is a perfect example of what money and fame will do to your soul if you let it. It’s not fair for me to say that they love their thrust to stardom more than their kids but it doesn’t look good for them. I have been watching the show since it started and while my manhood just took a hit for admitting that, I really did like it. It was a “feel-good” show that reminded us that there is still family value programing  in television. Well, when the bucks started flowing, Kate started jet-setting across the country on book tours and Jon changed from mild-mannered prep to biker-douche, the show’s premise took a backseat. And that premise is their beautiful kids. I can only imagine how confused all those kids are right now.

What the fuck is The Hills? Is it a reality show or are they actors? I breeze past MTV while channel surfing because if you stay on that channel too long you risk getting what doctors call hippodropadumpess where you will actually shit your own hippocampus. It’s true. Look it up. Anyway, my friend is a huge Hills fan and I just don’t get it. But it’s safe to say that the dickhole above needs to be killed off the show. So, I kind of hope it is a reality show after all.

I’m going to say it. If I disappear than you will know they got me. Oprah sucks. Now before the men in black take me away for slandering one of the top people who control the world let me explain. My mom is a big fan of hers. Anything that Oprah says is good, Mom will buy. Anything that Oprah says is bad, Mom will denounce. There is such a large demographic that her show reaches Oprah has the ability to control the masses. She controls my mother. Hopefully she hasn’t already gotten to you.

When I asked Mom why she was such an Oprah follower she told me that Oprah was very personable and was easy to identify with. I had no idea that she can identify with a multi billionaire that has a yacht the size of the USS Roosevelt and has a staff that contractually obligated to secrecy. In that case, Mom must think I am from the planet Plee Blip.

I have a theory that Oprah eats children. Oops, I have said too much. They are definitely coming for me now.

I think I need to read more books.

Edit: Just finished watching “Brothers and Sisters” on ABC.  It’s a good thing that I don’t believe in guns (as a non hunter) because I would have shot myself. Most likely blown off Rupert. That show probably gave me diabetes. There is a point when ‘cute’ is ’sick’. This show…fuck. There are no words. Ok, there are. But I can’t say that infront of the ladies.

It was the August of 1997. I was doing my PhD at Department of Anatomy, Bursa, Turkey. It was a very hot day. I was reading some textbooks for my PhD dissertation topic. My brain was melting in my skull. It was like a beef steak in a pot burning. I decided to go the library where there is air-conditioner, and I would do some literature search as well. I do not know why I did that, but I entered the key words “anatomy” and “psychiatry”. Well, I had no idea what I was expecting to find. Wait a minute! There were some articles; particularly on schizophrenia. Here I was a happy camper at Anatomy Department teaching and learning anatomy, and there was my other passion psychiatry research which I had no idea on. It took me seconds to be back at the Department from the library. Since that day, for the last 12 years, I have been doing research on the anatomy of psychiatric disorders, particularly on mood disorders (i.e., major depression and bipolar disorder).

This is my story. But what is the story of “the anatomy of psychiatric disorders”? Here we go.

First of all, I can talk hours and hours on that, and I do promise to summarize everything in the following six paragraphs.

Wouldn’t it be nice to examine the brain of a person when the person is living? This question led into a big change in neuroscience. Before, it was an animal study, or a study during a brain operation, or post-mortem study (the brain of the deceased patient). But after the 80s with computerized tomography (CT) , and late 80s we see that brain researchers started to use magnetic resonance imaging (MRI); it was non-invasive and there was no radiation exposure; and most important of all a high quality of resolution compared to that of CT. As a result, we had the chance to see what was happening in the brains of patients with neurology and psychiatry, and neurosurgery while they were alive.

When I say structural MRI (magnetic resonance imaging; sMRI 1-2) I mean the quantitative measurements (mostly volume of any given brain structure) in the brain. We use this term very often, so I have left it as it is but you should know that it is about the brain. So you got the definition, right? Brain structures’ volumes (or very rarely areas ; particularly in the past just before 90s) are measured through MRI in a group of patients with a psychiatric (or neurological) disorder and at least age- and gender- matched healthy controls. We compare the volumes and see if there is any change; mostly decrease in that brain structure in the psychiatric patient group compared to a control group.

Structural MRI has the importance of detecting the affected structure in any psychiatric disorder. This was the first benefit from sMRI. For example, it is hippocampus for schizophrenia, it is amygdala for autism, etc.

The first question to be answered would be “is there any change in the size “volume” of that structure in the patient group. Second would be why. This comes to the famous question of quantitative MRI (another name for structural MRI) egg or chicken? So let’s say we are measuring the most famous structure to be measured in the brain “the hippocampus” on which I have spent 12 years. Hippocampus will be another post, but it is about memory and emotional regulation, so let’s say we are measuring it in depression (not surprising,no? considering its main functions). Hippocampal volume is decreased in patients with major depression compared to matched healthy controls. That is our finding.Ok? So are the patients depressed because they have smaller hippocampus or they have smaller hippocampus because of their depression. Here is a neat post from Dr. Kramer @ Psychology Today on that topic. You can ask this question in any psychiatric disorder.

Here in Canada, I have been working on a dataset where one of the main questions (maybe the main) was the effect of medication on these changes in the volume. Another question? Effect of genetics. Research is to ask the right questions after all. There are more questions you can ask through structural MRI, but it has been loosing its importance in the neuroimaging world since the beginning of 21st century.

Before I finish, I will answer the question: how are you measuring the volume of a brain structure on MRI? Let’s go back to history for that. Bonaventura Cavalieri was an Italian mathematician. He came up with the Cavalieri’s principle that set the rules of the scientific discipline; stereology. What is that? Simply it is used for measuring the volume of something from a two-dimensional environment; let’s say an image, a picture. I was at a stereology course in Samsun, Turkey in 1997. Let me give a simple example they gave us at the course. Take a cucumber. No, don’t eat it. We are going to measure it. Cut the cucumber in slices, with exactly the same slice thickness. Let’s say 1 cm. Now measure the area of each slice, and multiply it with your slice thickness, well you have an estimate volume of the cucumber. Of course, stereology is not all about this, but sMRI uses this principle of stereology. It is not difficult to explain what I am doing as a researcher when I am at a party. But, the difficult task is to define the brain structure of which I need to trace in each slice the structure is seen. When I say trace I mean drawing its boundaries with a specific program; our program was AFNI; a free program that runs in Linux. The program gives you the data you need when you are done tracing the structure so you get the volume. The boundary in the four directions (e.g., above, below) in a scan like this. Of course, your important task would be to decide in which slice I should start measuring and till which slice I should keep on measuring. Here is my volumetric measurement protocol of hippocampus on MRI.

Here is my very first structural MRI paper published in the first issue of Neuroanatomy.

Here is a more recent one titled ” A meta-analysis examining clinical predictors of
hippocampal volume in patients with major depressive disorder“

If you are a beginner, I recommend you to check the web pages of the big labs where they study the volumetric analysis of brain structures in psychiatric disorders or enter in PubMed; -the google of medical research- the keywords “MRI” “volume” “the brain structure you are interested in” and “the psychiatric disorder you are interested in”. And see what happens…

Below is a list of 19 big important players around the world who study structural MRI. The names are listed randomly.

Ludberg Tebartz van Elst

Freiburg, Germany

Epilepsy; mood disorders, particularly major depression

Chris Pantelis

Melbourne,Australia

Schizophrenia & mood disorders

Arthur Toga

Los Angeles, USA

Schizophrenia

Raquel E. Gur

Pennsylvania, USA

Schizophrenia

Matcheri S. Keshavan

Detroit, USA

Schizophrenia

Stephen Lawrie (* a youtube video)

Edinburgh, Scotland

Schizophrenia

Nancy C. Andreasen

Iowa, USA

Schizophrenia

HE Hulshoff Pol

Utrecht, Netherlands

Schizophrenia

Naftali Raz

Detroit, USA

Aging

Jens C. Pruessner

Montreal, Canada

Alzheimer’s Disease

J. Douglas Bremner

Atlanta, USA

Major depression

Paolo Brambilla

Udine, Italy

Schizophrenia, mood disorders

Yvette I. Sheline

Washington, USA

Major depression

Allan L. Reiss

Stanford, USA

Autism

Martha Shenton

Harvard, USA

Schizophrenia

Eva M. Meisenzahl

Munchen, Germany

Major depression

Wayne C. Drevets

NIMH (National Institute of Mental Health), Bethesda, USA

Major depression, bipolar disorder

Deborah Yurgelun-Todd

Harvard, USA

Schizophrenia, bipolar disorder

Jair C. Soares

Houston, USA

Major depression, bipolar disorder

“İnsanların çoğu kaybetmekten korktuğu için, sevmekten korkuyor. Sevilmekten korkuyor, kendisini sevilmeye layık görmediği için. Düşünmekten korkuyor, sorumluluk getireceği için. Konuşmaktan korkuyor, eleştirilmekten korktuğu için. Duygularını ifade etmekten korkuyor, reddedilmekten korktuğu için. Yaşlanmaktan korkuyor, gençliğin kıymetini bilmediği için. Unutulmaktan korkuyor, dünyaya iyi birşey vermediği için. Ve ölmekten korkuyor aslında yaşamayı bilmediği için…”

William Shakespeare’in “korku” hakkındaki bu sözleri beni korkunun kaynağına yani beyne yöneltti. Gelin birlikte bu kaynağı-fabrikayı yani beyni gezelim ve özellikle “korku”nun ve ondan açığa çıkan diğer duyguların bu fabrikada nasıl işlendiğine bir göz atalım…

Fabrika yani üreten kaynak “beyin” ve bu fabrikadaki binlerce işçi (nöron), kendine ulaşan bilgileri işlemekle, ortaya koymakla her an meşguldür. Ortaya koydukları işin vasıflarına göre sınıflanmış nöronlar, gruplar halinde kendilerindeki bilgi doğrultusunda gece ve gündüz, uyku hali ya da uyanıklık hali gibi durumlarla sınırlanmadan, yani bu durumlar onlar için bir şey ifade etmeden, “ölüm” denen tecrübeye kadar devamlı olarak çalışmaktadırlar. İşte bu nöron gruplarından biri olan ve özellikle korkuları, bu korkulardan doğan vehim, vesveseleri gibi pek çok duyguları oluşturan, “badem (amigdala-amygdala)” işçi grubu, beynin yani fabrikanın bir ucunda, limbik sistem denilen bölümde sağ ve sol iki küçük gruptan oluşmaktadır. Onlar için kısaca “duygusal beyin merkezi” denilebilir. Özellikle “korku”nun kaynağıdır, yaratıcısıdır. Limbik sistemdeki diğer grup olan “hipokampusla (hippocampus)” -ki bu grup anıların deposudur- koordineli bir biçimde çalışmaktadırlar. Hipokampus depolanmış bilgileri, anıları sinapslara yani elçilere, basit anlamda bioelektriksel olarak yükleyerek amigdalaya gönderir. Burada bu bilgiler “duygusal” nitelik taşıyan etiketlerle etiketlenerek, şablonlar halini alır ve tabii bu duygusal davranışların tepkimeleri yani ortaya çıkmaları da genellikle başta “korku” olarak nitelendirebileceğimiz davranışlar olarak fiile dökülür.

Eğer işin biraz daha derinine inersek…

Fabrikada değer yargıları ve şartlanmalarla programlanmış veri tabanı (data base) kaynaklı edinilen bilgiler ışığı altında amigdala, kendisine ulaşan her bilgiye “bu bana zarar verir mi?”, “bundan nefret eder miyim?” gibi sorularla vücuttaki hormonların yani belirli bir grup hücrenin çalışmasına sebep olur, bu üretilen bilginin hormonlar aracılığı ile “kardiyovasküler sistem”, “kaslar”, “bağırsaklar” adı altındaki diğer hücre gruplarını aktive ederken aynı anda da beyin köküne “daha hızlı nefes al, kan basıncı artsın!, hazım engellensin” gibi bilgileri geçerek çeşitli reaksiyonları oluşturur. Tabii bu gibi aktiviteleri yapmasının bir açıdan başlangıç diyebileceğimiz noktası, kendisine ulaşan bilgileri önceden kendisinde işlenmiş olan bilgilerle yani veri tabanındaki (data base) mevcut olan bilgilerle bir takım bağlantılar kurarak ve her bilgiye “duygusal” bir etiket yapıştırarak gerçekleştirmiş olmasıdır.

Bize “göre” “geçmiş” diye adlandırdığımız bir noktada yaşanmış “korku” etiketi altındaki bir bilgi, amigdalada mevcut olduğu için bir bakıma “ayna” fonksiyonu ile yani yansıtma, bir nevi “ tekrar görüntüleme” şeklinde o bilginin tekrar yaşanmasını ya da benzer bir deneyimin oluşmasına sebep olabilir. Örneğin, büyük bir gürültü duyduğunuzda, amigdala hemen bu gürültü ile ilgili daha önceki bilgiden ortaya çıkmış duyguları aktive ederek, aynı duyguların benzer olayda tekrar yaşanmasını sağlar; eskiden oluşmuş duygular, o yeni bilgiye- duruma aynı şekilde kopyalanıp, adapte edilir.

Görsel ya da duyuşsal durum dışında, bizim dışımızdaki(!) kişilerin yaşadığı duygusal durumlarda da aynı duygunun bizde de açığa çıkması, yansıması kaçınılmazdır. Prof. Dr Marcola Iacoboni bu durumu “ayna nöron”larla açıklamaktadır. Ona göre, karşımızdaki bir kişinin yaşadığı duygusal bir durum, ayna nöronlar vasıtası ile bizim beynimizdeki amigdalada daha önce yaşadığımız benzer duygusal durumlarla eşleşip, bizden de aynı şeklide açığa çıkabilmektedir.

Bu öylesine ilginç bir oluşumdur ki, amigdala herhangi bir “korku” ya da “endişe” etiketli kendisindeki ya da dışında diye algıladığı başka(!) birisindeki mevcut bilgiyi “duygusal” olarak etiketleyip, depolarken, bir yandan da buna benzer yeni bilgileri de oluşturduğu şablonlarla etiketleyip “süregiden bir korku-endişe-vesvese bilgisi zinciri” oluşturmaktadır.

Veri tabanımızdaki (data base) mevcut olan ve amigdalada “duygusal” olarak etiketlenen bilgiler ve bir de yeni bilgilerin de eski bilgilerle kıyaslanarak, işlenmesi bizleri tamamen “duygusal” bir girdaba sokmakta ve bu girdabın en kuvvetli elemanlarından olan “korku” ise tüm duygulara sanki hükmederek, zaman zaman akıl ve iradeyi devre dışı bırakmaktadır. Çünkü, beyinde yani bu fabrikada akılcıl olarak işlerin yürütülmesini sağlayan ve koordine eden “neokorteks (neocortex)”, limbik sisteme ulaşan bilgiyi amigdalanın tersine daha sağlıklı değerlendirip, yorumlayarak işlemden geçirerek limbik sisteme geri yollarken, amigdala kortekse göre daha hızlı işlem yapar ve kendisine gelen bilgiyi önceki bilgilerden birisine benzerlik gösterdiği anda uygunluğunu tespit edip, etiketleyip limbik sisteme geri yollaması ve ana işletim sistemde yerini almasını sağlar. Bu da bizim dışardan çoğu kere “duygusal” bazlı “fevri- önyargılı-vesveseli” davranış dediğimiz çıktılara yani fiillere sebep verir.

İşte bu gibi duyguların aklın önüne geçip, ortaya çıkması, bilincin hakikatine yönelik yaşamasını engelleyebilmektedir. Bundan dolayı, amigdalanın bu yöndeki duygusal etiketleme işleminin önüne geçmenin tek yolu, “iman” gücüdür. Bakın bu durumu Üstad Ahmed Hulûsi de 1996 yılında yazdığı“İslâm” adlı kitabının “Cehennemden Ne İle Çıkılır” bölümünde nasıl açıklamış:

“… insan, hayatını cehenneme çeviren vehim gücünün üstesinden akılla gelemez!. Vehim kuvveti yani “yoku var sanıp, varı yok sayma” özelliğinin üstesinden gelecek olan insandaki güç akıl değil, imandır!. Vehim, akıl ve ona dayalı olan tefekkür mekanizması üzerinde rahatlıkla tasarruf ederken, fiilleri direkt yoldan etkileyen iman karşısında daima yenik düşer!. İşte bu yüzdendir ki “Dini” anlaması için akıllıya teklif yapılmış ve iman ederek yürümesi önerilmiştir!.
İnsanın, gerek dünya yaşamındaki cehennemî sürec, ve gerekse de ölümötesi yaşamındaki cehennemi, hep onda galip gelen vehim kuvvesinin sonucudur!. Bunun sona erdirilmesi ise yalnızca iman kuvvesi ile mümkündür!…”

“

Sonuç olarak, beynimizde yani fabrikada çalışan iki küçük badem büyüklüğündeki grubun beynimiz üzerindeki duygusal etiketli (korku-endişe-vesvese gibi…) etkilerinin hakikati anlamaya ve yaşamaya doğru yol alan beyinler için farkedilmesi gereklidir. Bu farkedişle birlikte, atılacak adım, beynimizde mevcut olan sonsuz sayıdaki “Mutlak Bilinç”e ait özellikleri keşfederek, bu yönde, bu inanç doğrultusunda bilgilerin açığa çıkmasını sağlamaya çalışmaktır. Buna inanmak öylesine bir güçtür ki, hakikatimize ulaşmakta bize engel oluşturacak duygusal etiketleri ve etkilerini silip, yok edebilir.

“Anatomy of the soul” is a short science-fiction movie project I have made 4 years ago to present during a seminar on hippocampus at the University of California San Francisco where I was doing my post-doctoral fellowship at a psychiatry neuroimaging lab. I did the movie using power point slides. The song used is “2025-Ucuncu ve Son Yolculuk- 2025 -The Third and Last Journey” by a Turkish ethnic/psychedelic Rock musician Baris Manco.

Most people play Quake with a computer mouse, but researchers in David Tank’s lab at Princeton have done it with a living mouse, AND they are recording the intracellular activity of individual neurons of the mouse during the gaming session. As reported in Intracellular dynamics of hippocampal place cells during virtual navigation, the virtual reality environment of the video game was sufficiently realistic to generate place cell activity in the mouse’s hippocampus. 

Now where did I see that cheese power-up?

Place cells modulate their activity dependent on the location the mouse is at. They have mostly been identified with extracellular recordings in freely moving mice. Extracellular recording only permits the detection of the rates of action potential firing, rather then the subtle intracellular voltage changes that could help explain the mechanism of place cell activity generation.  A few pioneers, such as Albert “my greatest strength is a tremendous capacity for boredom” Lee, have recorded intracellularly in freely moving animals, but these experiments are fiendishly difficult, as the motion of the animal’s head tends to break the seal on the recorded neuron.  Only a few cells have been recorded in that manner for more than a few minutes, though the success rate has been improving recently.  

Experimental setup

In Chris Harvey’s technique, they fix the head of the mouse to a bar and let the mouse walk on a floating ball, while a virtual reality screen is projected in the mouse’s field of view.  The motion of the ball controls the motion on the screen.  The head never moves, so intracellular recordings can be made relatively easily and held for long periods of time.

The authors find three characteristics of place cell activity that could explain their generation and function.

“An asymmetric ramp-like depolarization of the baseline membrane potential, an increase in the amplitude of intracellular theta oscillations, and a phase precession of the intracellular theta oscillation relative to the extracellularly recorded theta rhythm.” 

Intracellular voltage dynamics in place cells

These could be used to explain how place cells remap their selectivity when a mouse (or a human) moves into a new environment.  This also could be used to do more in depth studies of the mental replay of place locations that has been previously recorded in the activity patterns of the hippocampus.  The technique itself is about as sexy as neuroscience gets.  Unfortunately, this paper also provides an additional piece of evidence for Karel to use in motivating lab post-docs, “Look at Chris, he left the lab after you got here and already has a Nature article…”‘

A recent analysis of brain structure in healthy individuals who carry a common 2,445-bp deletion in intron 2 of the doublecortin domain containing 2 (DCDC2) gene found that heterozygotes for the deletion showed higher grey matter volumes for several brain areas known to be involved in the processing of written and spoken language (superior, medial and inferior temporal cortex, fusiform, hippocampal / parahippocampal, inferior occipito-parietal, inferior and middle frontal gyri, especially in the left hemisphere) [doi:10.1007/s11682-007-9012-1].  The DCDC2 gene sits within a well known locus frequently found to be associated with developmental dyslexia, and associations of reading disability with DCDC2 have been confirmed in population-based studies.  Further work on DCDC2 (open access) shows that the DNA that is deleted in the 2,445-bp deletion in intron 2 carries a number of repeating sequences to which developmental transcription factors bind and that inhibition of DCDC2 results in altered neuronal migration (the right-hand panel shows altered radial migration when DCDC2 is inhibited).  Perhaps the greater grey matter volumes are related to this type of neuronal migration finding?  Will be interesting to follow this story further!

*published Oct. 11, 2009

BY VANESSA C. DEGGINS
Authorities and psychiatrists say letting children and teens drink alcohol only increases long-term risks.

Homecomings, proms and graduations are annual events often accompanied by parties.

At those times, parents often rationalize allowing their teenagers to consume alcohol.

“Parents have a million reasons,” said Mary Kaye Allemond, program director for the Calcasieu Parish Office of Juvenile Justice Services. “Parents think, ‘they are going to drink anyway, so I might as well let them drink in my house,’ or ‘it’s a rite of passage, everyone drinks in Louisiana.”’

Allemond and health officials said most parents don’t realize the damage that is done when a teenager drinks.

“I always have to explain the medical side to parents who think the legal drinking age should be 18,” said Allemond, who has teenage children.

Psychiatrists at Lake Charles Memorial Hospital said drinking at an early age not only interrupts brain development, but may destroy areas of the brain that, if developed, would prevent a person from becoming addicted later in life.

“Between 14 and 20 years old is when all of the neuron connections are developing very quickly,” said Dr. Sreelatha Pulakhandam, who specialized in pediatric psychiatry.

The hippocampus and prefrontal cortex parts of the brain control memory and behavior.

“If both of those parts of the brain are smaller, it sets the teenager up to be behind on everything for the rest of their lives,” Pulakhandam said.

Pulakhandam laid out an ominous cycle: A weak memory affects learning ability. This would be exasperated by sleep deprivation caused by drinking. Peer pressure pushes the teenagers not only to drink, but drink large amounts.

“The chances of high-risk behavior, like unsafe driving, unprotected sex, are much higher while drinking,” Pulakhandam said.

Pulakhandam said the chances of suicide and depression also increase.

The Louisiana Caring Communities Youth Survey 2008 results show a steady increase in alcohol use by teenagers. The survey, conducted every two years, anonymously polls students in sixth, eighth, 10th and 12th grades about drug and alcohol use.

Calcasieu Parish results

When students were asked if they had an alcoholic beverage in the past 30 days, 9.3 percent of sixth-graders said yes, and the numbers steadily increased with age. For eighth graders, it was 26.1 percent; for 10th graders, 41.4 percent; and for 12 graders, 50.7-percent.

“With Louisiana culture, just about everything we do is targeted around alcohol,” said Allemond. “We drink at crawfish boils, barbecues, sporting events. So parents think it’s no big deal if the kids have a sip.”

Allemond said the Office of Juvenile Justice is focusing on changing attitudes by letting people know that what’s considered normal is actually hazardous for teenagers’ health.

When students were asked if they had been binge drinking in the past two weeks, 4.8 percent of sixth-graders said yes. And the answer was yes for 13.1 percent of eighth graders, 19.9 percent of 10th graders and 29 percent of 12th graders.

The survey defines binge drinking as having five or more alcoholic drinks in a row.

Allemond said parents have openly discussed providing alcohol at teenage parties in their homes, saying they feel they are helping keep them safe.

“I tell them all of the time, at these parties teenagers don’t have one beer. They are drinking as much as possible,” Allemond said. “Kids think they’re invinsible anyway. What are they going to think when we condone this?”

Focus on parents

Dr. Misty Kelly, director of psychiatric services at Lake Charles Memorial, said along with changing cultural norms, there are a lot of parenting issues to fix.

“In our in-patient program, we see a lot of children who start drinking to cope with family conflict or stresses in the home and at school,” Kelly said.

“A lot of parents are naïve, and they are not actively involved in their children’s lives or who they hang out with,” Kelly said. “The kids are pushed out, independent, and the parents are just busy with their own lives.”

A study by the Pacific Institute for Research and Evaluation estimated that underage drinking cost the residents of Louisiana $1.1 billion in 2005.

Those costs included $312.1 million on youth traffic crashes, $107.7 million on the outcomes of high-risk sex for people ages 14 to 20 and $21.6 million on fetal alcohol syndrome among mothers ages 15 to 20.

The Institute estimated that in 2005, underage drinkers consumed 14.7 percent of all alcohol sold in Louisiana, or about $305 million in sales.

Local law enforcers have said they do not have the manpower for patrols targeting underage drinking, but they encourage students and parents to report parties or places where juveniles are allowed to drink.

The main state criminal charge an adult could face for serving alcohol or drugs to someone under the age of 17 is contributing to the delinquency of juveniles.

The Office of Juvenile Justice is working on a grant that authorities could use to fund law enforcement patrols.

link: http://bit.ly/2Va4z

Love and monogamy in the Syngnathid fishes (Hippocampus and related genera)

Dr. Calvin Cheung, quack PhD

Zoological Research, Department of Biological Sciences, University of Alberta.

Abstract:

Monogamy is defined as a type of mating system in which one male and one female mate exclusively with each other within a breeding season.  Although rarely observed among fishes, it has been exceptionally well-documented among the Family Syngnathidae: comprising of the seahorses (Hippocampus) and pipefish (Corythoichthys).  Both genera are noted for their peculiar appearance and intriguing behaviour.  One of these behaviours includes daily morning greetings, during which the two individuals perform a synchronized dance.  This dance has been hypothesized to play an important role in the establishment and maintenance of a long-term pair-bond relationship (Vincent, 1995; Sogabe and Yanagisawa, 2007).

My education is jam-packed with such trivial information, but this one in particular kinda got me thinking.  Similar to fishes, monogamy is also extremely rare among mammals.  Humans, as we all know, are also mammals and it is interesting to believe that perhaps we, too, may be capable of enveloping this type of relationship much to the demise of the promiscuity of today’s society.

From a non-mammal to mammal concomitance; from fish biology to human society… Monogamy and social behaviour in the Syngnathids may have implications with human behaviour, existing in a philosophical context through parallel evolution or through a distant plesiomorphic trait known as love and emotion.

Because they belong to the sole taxon whose members exhibit the single case of male pregnancy in the entire animal kingdom, this speculation is arguably a bizarre personification of sea horse life history. Be grateful … I’ll spare you the scientific mumbo jumbo behind this fact; you can thank me later.   Perhaps the concept is simply a reflection of my background as a zoology ge…er…major … or perhaps I am simply out of my mind … but anyhow …

I watch another pass me by.  Year after year I sit on my chair and ponder.  I have always believed that true love is forever… that true love is unconditional.  Yet, every time I meet someone I think I’ve fallen for, in due time things would never work out the way I picture in my mind, and I ultimately force myself to forget.  So what exactly is true love?  Contrary to my beliefs, it is clearly not a feeling I have already encountered… but one thing is for sure.  With each and every new relationship I feel a little stronger, a little more passionate.  I feel as though with every let down I am able to bounce back higher than ever before, and when I meet the one who truly deserves, my heart will shine upon her in its greatest luminescence.

In other words, if every morning I could …

Wake up and enjoy the scenic beauty of the coral reefs in your eyes

Feel the gentleness of a passing stream when you breathe against my neck

Sense the perfect aura of a goddess of the sea at the touch of your fingertips

And taste the sweet tenderness of passion in your lips,

Like a mermaid breathing new life into my being

As I float into the realm of your underwater paradise …

It would make a world of a difference for my future, for my life

Even if you cannot be there for me at this very moment,

With just the very existence of your spirit by my side

And the knowledge of the reciprocation of these very thoughts within your mind

I will have obtained the strength necessary to move forward each stage,

To take the gradual steps leading towards the one day …

Towards the onset we have destined for each other

In the meantime all I have to do is prove my worth

Concentrating on my career, my growth, my development…

I am determined … but most importantly …

I am happy …

If a Hippocampus male can spend years searching an entire ocean for its life-partner, how can I possibly give up now?  We Homo sapiens are supposed to be a superior, more intelligent species yet it is a damn shame how often love is taken for granted in society.  Personally I hate conformity… so I strive to make a difference.

When I find the one who is right for me, I daresay we will achieve the anthropogenic equivalent to the pair-bond of any seahorse couple, and thus will become inseparable … ‘til death do us part.

And so, whoever you are, wherever you are, I would like you to know that although it has been difficult … in light of it all … everything is beautiful.

From the depths of my heart,

Cal

Will you dance with me?

References:

Sogabe, A., and Y. Yanagisawa.  2007.  The function of daily greetings in a monogamous pipefish Corythoichthys haematopterus.  Journal of Fish Biology 71: 585-595.

Vincent, A.C.J.  1995.  A role for daily greetings in maintaining seahorse pair bonds.  Animal Behaviour 49: 258-260.

In Robert Sapolsky’s book, “Why Zebras Don’t Get Ulcers“, he details a biological feedback system wherein psychological stress leads to the release of glucocorticoids that have beneficial effects in the near-term but negative effects (e.g. ulcers, depression, etc.) in the long-term.  The key to getting the near-term benefits and avoiding the long-term costs – is to be able to turn OFF the flow of glucocorticoids.  This is normally dependent on circuitry involving the frontal cortex and hippocampus, that allow individuals to reset their expectations and acknowledge that everything is OK again.  Here’s the catch (i.e. mother nature’s ironic sense of humor). These very glucocorticoids can initiate a kind of reorganization or ’shrinkage’ to the hippocampus  – and this can disable, or undermine the ability of the hippocampus to turn OFF the flow of glucocorticoids.  Yes, that’s right, the very switch that turns OFF glucocorticoid flow is disabled by exposure to glucocorticoids!  Can you imagine what happens when that switch (hippocampus) get progressively more disabled?  Your ability to turn OFF glucocorticoids gets progressively worse and the negative effects of stress become more and more difficult to cope with.

Sounds depressing.  Indeed it is, and there are many findings of reduced hippocampal volume in various depressive illnesses.  The complex problem at hand, then, is how to reverse the runaway-train-like (depression leads to glucocorticoids which leads to smaller hippocampus which leads to more depression) effects of stress and depression?

One new avenue of research has been focused on the ability of the hippocampus to normally produce new cells – neurogenesis – throughout life.  Might such cells be useful in reversing hippocampal remodeling (shrinkage)?  If so, what molecules or genes might be targeted to drive this process in a treatment setting?

The recent paper by Joffe and colleagues, “Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: Implications for depressive illness” [doi: 10.1002/hbm.20592] offers some key insights.  They examined 467 healthy participants of the Brain Resource International Database (a personalized medicine company with a focus on brain health) using personality tests, structural brain imaging and genotyping for an A-to-G variation (valine-to-methionine) polymorphism in the BDNF gene.  They report that lower volume of the hippocampus was associated with higher scores of neuroticism (worriers) – but, this negative relationship was not found in all people – just those who carry the A- or methionine-allele.  Thus, those individuals who carry the G/G (valine/valine) genotype of BDNF may be somewhat more protected from the negative (hippocampal remodeling) effects of psychological stress.  Interestingly, the BDNF gene seems to play a role in brain repair!  So perhaps this neuro-biochemical pathway can be explored to further therapeutic benefit.  Exciting!!

By the way, the reason zebras don’t get ulcers, is because their life revolves around a lot of short term stressors (mainly hungry lions) where the glucocorticoid-stress system works wonderfully to keep them alive.  Its only homo sapiens who has enough long-term memory to sit around in front of the TV and incessantly fret about the mortgage, the neighbors, the 401K etc., who have the capacity to bring down all the negative, toxic effects of chronic glucocorticoids exposure upon themselves. My 23andMe profile shows that I am a G/G valine/valine … does this mean I’m free to worry more?  Now I’m worried.  More on BDNF here.

Joseph LeDoux’s book, “Synaptic Self: How Our Brains Become Who We Are” opens with his recounting of an incidental glance at a t-shirt, “I don’t know, so maybe I’m not” (a play on Descartes’ “cogito ergo sum“) that prompted him to explore how our brain encodes memory and how that leads to our sense of self.  More vividly, Elizabeth Wurtzel, in “Prozac Nation” recounts, “Nothing in my life ever seemed to fade away or take its rightful place among the pantheon of experiences that constituted my eighteen years. It was all still with me, the storage space in my brain crammed with vivid memories, packed and piled like photographs and old dresses in my grandmother’s bureau. I wasn’t just the madwoman in the attic — I was the attic itself. The past was all over me, all under me, all inside me.” Both authors, like many others, have shared their personal reflections on the fact that – to put it far less eloquently than LeDoux and Wurtzl – “we” or “you” are encoded in your memories, which are “saved” in the form of synaptic connections that strengthen and weaken and morph through age and experience.  Furthermore, such synaptic connections and the myriad biochemical machinery that constitute them, are forever modulated by mood, motivation and your pharmacological concoction du jour.

Well, given that my “self” or “who I think of as myself” or ” who I’m aware of at the moment writing this blog post” … you get the neuro-philosophical dilemma here … hangs ever so tenuously on the biochemical function of a bunch of tiny little proteins that make up my synaptic connections – perhaps I should get to know these little buggers a bit better.

OK, how about a gene known as kalirin – which is named after the multiple-handed Hindu goddess Kali whose name, coincidentally, means “force of time (kala)” and is today considered the goddess of time and change (whoa, very fitting for a memory gene huh?).  The imaginative biochemists who dubbed kalirin recognized that the protein was multi-handed and able to interact with lots of other proteins.  In biochemical terms, kalirin is known as a “guanine nucleotide exchange factor” – basically, just a helper protein who helps to activate someone known as a Rho GTPase (by helping to exchange the spent GDP for a new, energy-laden GTP) who can then use the GTP to induce changes in neuronal shape through effects on the actin cytoskeleton.  Thus, kalirin, by performing its GDP-GTP exchange function, helps the actin cytoskeleton to grow.  The video below, shows how the actin cytoskeleton grows and contracts – very dynamically – in dendrites that carry synaptic spines – whose connectivity is the very essence of “self”.  Indeed, there is a lot of continuing action at the level of the synapse and its connection to other synapses, and kalirin is just one of many proteins that work in this dynamic, ever-changing biochemical reaction that makes up our synaptic connections.

In their paper”Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes” [doi: 10.1073/pnas.0904636106] Michael Cahill and colleagues put this biochemical model of kalirin to the test, by examining a mouse whose version of kalirin has been inactivated.  Although the mice born with this inactivated form are able to live, eat and breed, they do have significantly less dense patterns of dendritic spines in layer V of the frontal cortex (not in the hippocampus however, even though kalirin is expressed there).  Amazingly, the deficits in spine density could be rescued by subsequent over-expression of kalirin!  Hmm, perhaps a kalirin medication in the future? Further behavior analyses revealed deficits in memory that are dependent on the frontal cortex (working memory) but not hippocampus (reference memory) which seems consistent with the synaptic spine density findings.

Lastly, the authors point out that human kalirin gene expression and variation has been associated with several neuro-psychiatric conditions such as schizophrenia, ADHD and Alzheimer’s Disease.   All of these disorders are particularly cruel in the way they can deprive a person of their own self-perception, self-identity and dignity.  It seems that kalirin is a goddess I plan on getting to know better.  I hope she treats “me” well in the years to come.

The neural correlates of recollection were examined using event-related functional MRI. We examined how the presence of different visual context information during encoding of target words influenced later recollection for the words presented alone at retrieval. Participants studied words presented with different pictures of faces or scrambled faces on each trial, and on a subsequent scanned recognition test made ‘remember’, ‘know’ or ‘new’ responses to words presented alone. Prior to the study phase, participants performed a localizer task, in which the fusiform face area (FFA) was identified. We compared brain activation patterns for remember and know responses given to words studied with faces as compared to scrambled faces. Though behaviourally participants showed no difference in memory performance depending on encoding trial type, both a group- and individual-based region-of-interest analysis showed increased activation in the functionally-defined FFA for remember responses given to words studied with faces compared to scrambled faces. A regression analysis additionally showed that activation in the right fusiform gyrus increased as the relative recollection benefit for words studied with meaningful (face) compared to non-meaningful (scrambled face) context information increased. Results suggest that context-specific brain regions implicated during encoding are recruited during retrieval, and that the degree to which participants activate context-specific brain regions during retrieval is related to a behavioural benefit in later recollection for target information presented alone.

from Neuropsychologia

In a recent Scientific American article, evidence is presented for multiple realizability.

What is multiple realizability? Let’s begin with functionalism. Functionalism is a dominant view in the philosophy of mind and concerns the relationship between the brain and the mind. Take a physical apparatus (such as the brain), and divide it into components each defined by what causes it, and what it causes. Functionalism is the view that the mind consists of such components. It has the consequence that different physical apparatuses can give rise to (or ‘realize’) the same components, so defined. Think for example, of all the different physical objects that can realize a corkscrew. They can be constituted and look very different. But they all share the same causal role.

Neuroscientist Larry R Squire has discovered that the physical states that realize memories change as the memories become more entrenched. They begin in the hippocampus. Over time the memories become entrenched ‘in’ the neocortex, until eventually the hippocampus is no longer needed and so no longer constitutes part of the physical realizer of a given memory.

For the original article go here.

 Related articles:
Multiple Realizability
By Eric Funkhouser , University of Arkansas
(Vol. 2, February 2007)
Philosophy Compass

Can Physicalism be Non-reductive?
By Andrew Melnyk , University of Missouri
(Vol. 3, November 2008)
Philosophy Compass

The September edition of DESE’s Instructional Technology newsletter announced that Hippocampus is now available for all Missouri school districts.

DESE and the Missouri Virtual Program (MoVIP) purchased a subscription to the National Repository of Online Courses (NROC) for all Missouri school districts, or Hippocampus as the collection is commonly called. …Over 2,500 multimedia learning objects are available at this site, including resources that cover four of the mandatory Missouri EOC exams (algebra I, biology, American government and US history).

I need to explore this resource more. But, so far I’ve watched a narrated civil war slideshow with illustrations, photos, and primary documents. I’ve previewed a few animation videos in the Science Physics area. Direct links to resources are provided, which is great for teachers to link to on their websites or bookmark. In math, a narrated alegbra problem is displayed with a box for submitting my answers. When I submit the incorrect answers to the rate problem, it displays how to find the correct answer. If I click the Topic Text button I can view information on solving rate problems and view an example.

There is a link teachers can use to create a custom HippoCampus page for their students. The standards tab is a convenient way to find resources tied to a specific Missouri standard. The Textbooks tab lists several books. When select, a list of multimedia resources is provided.

]]> http://devonseaglass.wordpress.com/2009/09/01/hippocampus-teignmouthus/ Tue, 01 Sep 2009 12:50:51 +0000 devonseaglass http://devonseaglass.wordpress.com/2009/09/01/hippocampus-teignmouthus/ http://ntldr1962uk.wordpress.com/2009/08/30/emotions-i/ Sun, 30 Aug 2009 23:40:20 +0000 Marcela http://ntldr1962uk.wordpress.com/2009/08/30/emotions-i/ http://genes2brains2mind2me.com/2009/08/22/timing-is-everything-k-channel-bears-the-evidence-across-milliseconds-and-millenia/ Sat, 22 Aug 2009 11:51:09 +0000 dendrite http://genes2brains2mind2me.com/2009/08/22/timing-is-everything-k-channel-bears-the-evidence-across-milliseconds-and-millenia/

**PODCAST accompanies this post** In the brain, as in other aspects of life, timing is everything.  On an intuitive level, its pretty clear, that, since neurons have to work together in widely distributed networks, they have a lot of incentive to talk to each other in a rhythmic, organized way. Think of a choir that sings together vs. a cacophony of kids in a cafeteria – which would you rather have as your brain? A technical way of saying this could be, “Clustered bursting oscillations, with in-phase synchrony within each cluster, have been proposed as a binding mechanism. According to this idea, neurons that encode a particular stimulus feature synchronize in the same cluster.“  A less technical way of saying this was first uttered by Carla Shatz who said, “Neurons that fire together wire together” and “Neurons that fire apart wire apart“.  So it seems, that the control over neural timing and synchronicity – the rushing “in” of Na+ ions and rushing “out” of K+ ions that occur during cycles of depolarization and repolarization of an action potential take only a few milliseconds – is something that neurons would have tight control over.

With this premise in mind, it is fascinating to ponder some recent findings reported by Huffaker et al. in their research article, “A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia” [doi: 10.1038/nm.1962].  Here, the research team has identified a gene, KCNH2, that is both differentially expressed in brains of schizophrenia patients vs. healthy controls and that contains several SNP genetic variants (rs3800779, rs748693, rs1036145) that are associated with multiple different patient populations.  Furthermore, the team finds that the risk-associated SNPs are associated with greater expression of an isoform of KCNH2 – a kind of special isoform – one that is expressed in humans and other primates, but not in rodents (they show a frame-shift nucleotide change that renders their ATG start codon out of frame and their copy non-expressed).  Last I checked, primates and rodents shared a common ancestor many millenia ago. Very neat – since some have suggested that newer evolutionary innovations might still have some kinks that need to be worked out.

In any case, the research team shows that the 3 SNPs are associated with a variety of brain parameters such as hippocampal volume, hippocampal activity (declarative memory task) and activity in the dorsolateral prefrontal cortex (DLPFC). The main suggestion of how these variants in KCNH2 might lead to these brain changes and risk for schizophrenia comes from previous findings that mutations in this gene screw up the efflux of K+ ions during the repolarization phase of an action potential.  In the heart (where KCNH2 is also expressed) this has been shown to lead to a form of “long QT syndrome“.  Thus, the team explores this idea using primary neuronal cell cultures and confirms that greater expression of the primate isoform leads to non-adaptive, quickly deactivating, faster firing patterns, presumably due to the extra K+ channels. 

The authors hint that fast & extended spiking is – in the context of human cognition – is thought to be a good thing since its needed to allow the binding of multiple input streams.  However, in this case, the variants seem to have pushed the process to a non-adaptive extreme.  Perhaps there is a seed of an interesting evolutionary story here, since the innovation (longer, extended firing in the DLPFC) that allows humans to ponder so many ideas at the same time, may have some legacy non-adaptive genetic variation still floating around in the human lineage.  Just a speculative muse – but fun to consider in a blog post.

In any case, the team has substantiated a very plausible mechanism for how the genetic variants may give rise to the disorder.  A scientific tour-de-force if there ever was one.

On a personal note, I checked my 23andMe profile and found that while rs3800779 and rs748693 were not assayed, rs1036145 was, and I – boringly – am a middling G/A heterozygote.  In this article, the researchers find that the A/As showed smaller right-hippocampal grey matter volume, but the G/A were not different that the G/Gs.  During a declarative memory task, the GGs showed little or no change in hippocampal activity while the AA and GA group showed changes – but only in the left hippocampus.  In the N-back task (a working memory task), the AA’s showed more changes in brain activation in the right DLPFC compared to the GGs and GAs.

For further edification, here is a video showing the structure of the KCNH2-type K+ channel.  Marvel at the tiny pore that allows red K+ ions to leak through during the repolarization phase of an action potential.   **PODCAST accompanies this post**

Among the various (and few) significant results of recent landmark whole-genome analyses (involving more than 54,000 participants) on schizophrenia (covered here and here), there was really just one consistent result – linkage to the 6p21-22 region containing the immunological MHC loci.  While there has been some despair among professional gene hunters, one man’s exasperation can sometimes be a source of great interest and opportunity for others – who – for many years – have suspected that early immunological infection was a key risk factor in the development of the disorder.

Such is the case in the recent paper, “Prenatal immune challenge induces developmental changes in the morphology of pyramidal neurons of the prefrontal cortex and hippocampus in rats” by Baharnoori et al., [doi: 10.1016/j.schres.2008.10.003].  In this paper, the authors point out that Emil Kraepelin, who first described the disorder we now call schizophrenia, had suggested that childhood inflammation of the head might be an important risk factor.  Thus, the immunopathological hypothesis has been around since day 0 – a long time coming I suppose.

In their research article, Baharnoori and colleagues have taken this hypothesis and asked, in a straightforward way, what the consequences of an immunological challenge on the developing brain might look like.  To evaluate this question, the team used a Sprague-Dawley rat model and injected pregnant females (intraperitoneally on embryonic day 16) with a substance known as lipopolysaccharide (LPS) which is known to mimic an infection and initiate an immune response (in a manner that would normally depend on the MHC loci found on 6p21-22). Once the injections were made, the team was then able to assess the consequences to various aspects of brain and behavior.

In this paper, the team focused their analysis on the development of the frontal cortex and the hippocampus – 2 regions that are known to function poorly in schizophrenia.  They used a very, very focused probe of development – namely the overall shape, branching structure and spine formations on pyramidal cells in these regions – via a method known as Golgi-Cox staining.  The team presents a series of fantastically detailed images of single pyramidal cells (taken from postnatal day 10, 35 and 60) from animals who’s mothers were immunologically challenged and those who were unexposed to LPS.

Briefly, the team finds that the prenatal exposure to LPS had the effect of reducing the number of dendritic spines (these are the aspects of a neuron that are used to make synaptic connections with other neurons) in the developing offspring.  Other aspects of neuronal shape were also affected in the treated animals – basically amounting to a less branchy, less spiny – less connectable – neuron.  If that’s not a basis for a cognitive disorder than what else is?  Indeed, the authors point out that such spines are targets – in early development – for interneurons that are essential for long-range gamma oscillations that help distant brain regions function together in a coherent manner (something that notably does not happen in schizophrenia).

Thus, there is many a reason (54,000 strong) to want to better understand the neuro-immuno-genetic-developmental mechanisms that can alter neuronal structure.  Exciting progress in the face of recent genetic setbacks!