Cocaine self-administration in mice with forebrain knock-down of trpc5 ion channels

Canonical transient receptor potential (TRPC) channels are a family of non-selective cation channels that play a crucial role in modulating neuronal excitability due to their involvement in intracellular Ca²⁺ regulation and dendritic growth. TRPC5 channels a) are one of the two most prevalent TRPC channels in the adult rodent brain; b) are densely expressed in deep layer pyramidal neurons of the prefrontal cortex (PFC); and c) modulate neuronal persistent activity necessary for working memory and attention. In order to evaluate the causal role of TRPC5 in motivation/reward-related behaviors, conditional forebrain TRPC5 knock-down (trpc5-KD) mice were generated and trained to nose-poke for intravenous cocaine. Here we present a data set containing the first 6 days of saline or cocaine self-administration in wild type (WT) and trpc5-KD mice. In addition, we also present a data set showing the dose-response to cocaine after both groups had achieved similar levels of cocaine self-administration. Compared to WT mice, trpc5-KD mice exhibited an apparent increase in self-administration on the first day of cocaine testing without prior operant training. There were no apparent differences between WT and trpc5-KD mice for saline responding on the first day of training. Both groups showed similar dose-response sensitivity to cocaine after several days of achieving similar levels of cocaine intake.  (for more see our recent publication)

Changing the Culture of “Ding”: Education, Legislation and Research on Concussive Brain Injury in Youth Athletics

How can we change the culture of minimizing an injury, often times referred to as a “ding” or “getting your bell rung”, to a culture recognizing that concussions are brain injuries? (for my full article published in Nature Precedings April 3 click here) The number of emergency department visits concerning sport related TBI in youth increased 57% from 2001 to 2009 and while a fraction of that increase may be attributed to injuries that were once missed now being identified due to greater general awareness, the fact remains that there are nearly 200,000 children every year who suffer sport related concussion or other TBI serious enough to prompt a visit to the ED. 40% of sports related concussions involve children between the ages of 8 and 13, and in this group the rate of concussion doubled between 1997 and 2007. The risk of concussion is highest in football and there are nearly 67,000 diagnosed concussions in high school football every year.

In other sports that males and females play, such as basketball, girls seem to be at a higher risk. In high schools, concussions account for 15% of all sports related injuries resulting in at least one day of play lost. The risk of a suffering a concussion when participating in a contact sport may be as high as 20% per season. In both girls’ and boys’ soccer and basketball 20% of the concussions were repeat concussions. These statistics just further illustrate the gravity of the problem of sport related concussions. Here we describe the need for more work on education, legislation and research in order to change in the concussion/mTBI culture.

The Utility of Oral Sex in the Fruit Bat

Thanks to Chinese scientists interested in the sexual proclivities of fruit bats, we now have some insight into the utility of oral sex. Libiao Zhang and colleagues at the Guangdong Entomological Institute published a paper in the open access journal, PLoS ONE, entitled, “Fellatio by Fruit Bats Prolongs Copulation Time“. The main thrust of the paper is that female bats lick the shaft and base, but not the glans of the penis during coitus and this results in a lengthening of the duration of copulation.

Now the teleological question raises its ugly head…what purpose does this serve? The authors offer a few tantalizing hypotheses for how this behavior emerged. They observed initial attempts to escape the male before the female bat, “licks the male penis to increase penile stimulation, stiffening the penis and maintaining the male’s erection. At the same time, the female’s saliva may increase lubrication, thus facilitating intromission and thrusting. In combination, these features may prolong copulation.” Their conclusions are not so ho-hum. They speculate further, “…we extend the interpretation of such behaviour beyond that of ‘pleasure giving’ into an evolutionary context. Importantly we show that fellatio increases the duration of copulation. This may have several important functions, for example increasing fertilization success, or even reducing the risk of contracting [sexually transmitted diseases]. The behaviour presumably favours the donor, although it may also benefit both partners especially if fertilization success is increased. It is conceivable that the female manipulates the male by increasing sexual stimulation, so that she ultimately benefits.”

It seems questionable that an increase in fertilization success should be considered a benefit to the parents as the authors suggest. After all successful fertilization results in hungry, screaming baby fruitbats that would only decrease the frequency and duration of their inverted sex acts. Furthermore, it is odd that the female fruit bat would perform fellatio as a means to prevent STDs. Although if there is evidence for this working in humans then expect vials of fruit bat saliva and drunken reassurances to soon penetrate the singles dating scene.

Despite my initial misgivings I eventually succumbed to the possible Ig Nobel prize worthiness of this work when I saw the raunchy supplementary video which was described as, “The face-to-back copulation of Cynopterus sphinx, showing the fellatio by female”. The gratuitous Chinese porn-style soundtrack that accompanied the fruit bat fellatio clip was artistic and increased the duration of my bat-sex voyeurism and it will likely have the same effect in you.

Fruit Bat Fellatio Movie!!!

Gulf War Syndrome: A role for organophosphate induced plasticity of locus coeruleus neurons

In 2008, more than 15 years after the Gulf War had ended, the US Government acknowledged the Gulf War Syndrome as a legitimate illness. That year a congressionally mandated Research Advisory Committee issued a 452-page report that stated, “scientific evidence leaves no question that Gulf War illness is a real condition with real causes and serious consequences for affected veterans. Because it wasn’t acknowledged as an illness there were no significant funds available to research the illness, so next to nothing was known about which brain regions might be involved.

In 2008, my laboratory obtained a VA sponsored contract to study the role of the toxic organophosphate metabolite, chlorpyrifos oxon on various brain regions in order to shed light into the cellular mechanisms of a number of psychological symptoms associated with deployed Gulf War veterans. Over the past few years, we have published a couple papers on the subject. Most recently, (July 8, 2011) we published our most recent findings in Nature Precedings implicating a brain region critically involved in attention, addition and arousal. Visit the site and Vote for our paper and leave us a comment there or at http://www.neuro-cloud.info if you are interested in collaborating with us on this project.

Abstract
“Gulf War syndrome is a chronic multi-symptom illness that has affected about a quarter of the deployed veterans of the 1991 Gulf War. Exposure to prolonged low-level organophosphate insecticides and other toxic chemicals is now thought to be responsible. Chlorpyrifos was one commonly used insecticide. The metabolite of chlorpyrifos, chlorpyrifos oxon, is a potent irreversible inhibitor of acetylcholinesterase, much like the nerve agent Sarin. To date, the target brain region(s) most susceptible to the neuroactive effects of chlorpyrifos oxon have yet to be identified. To address this we tested ability of chlorpyrifos oxon to influence neuronal excitability and induce lasting changes in the locus coeruleus, a brain region implicated in anxiety, substance use, attention and emotional response to stress. Here we used an ex vivo rodent model to identify a dramatic effect of chlorpyrifos oxon on locus coeruleus noradrenergic neuronal activity. Prolonged exposure to chlorpyrifos oxon caused acute inhibition and a lasting rebound excitatory state expressed after days of exposure and subsequent withdrawal. Our findings indicate that the locus coeruleus is a brain region vulnerable to chlorpyrifos oxon-induced neuroplastic changes possibly leading to the neurological symptoms affecting veterans of the Gulf War.

Love Bites, Love Bleeds…

Those of us in dating in high school in the late 80′s can attest to the stinging truth revealed in Def Leppard’s song, “Love Bites” shortly after a nasty break-up. But it was only recently that scientists employing state-of-the-art brain imaging fMRI technology have been able to view the similarities between the biting pain of rejection from a lover and physical pain.

A study published in the April 12 issue of Proceedings of the National Academy of Science (PNAS) has provided the most direct evidence showing a common brain circuit underlying the pain of rejection and physical pain.

In their study, the researchers at Columbia University, University of Michigan and University of Colorado, Boulder studied 40 subjects who had experienced rejection and break-up with a lover within the past six months. They tested each subject on two tasks, a social rejection task and a physical pain task, while imaging their brains.

In the scanner, subjects looked at the faces of their ex and thought about how it felt during their split and a snapshot of their brain was taken. Next they were shown a headshot of a friend of the same sex as their former partner and thought about a recent positive experience they shared. This provided the social rejection condition.

To compare the social rejection experience to the experience of “physical pain” they attached a thermal device to the volunteers’ forearms and set it to produced a “painful”, but not harmful level.

In both men and women, rejection and painful heat activated brain circuits underlying distress (e.g. Anterior Cingulate cortex) and the sensation of pain e.g. somatosensory cortex).

Although this seems seems intuitive from centuries of poetry, tragic plays and lyrics, knowledge at a mechanistic level showing the same circuits are activated gives scientists new ways to deal with both. It makes one wonder if taking pain-killers shortly after a break-up might be a treatment option.

The common mechanism between social rejection and physical pain may be one reason why heroin and alcohol, both analgesics for pain, are irresistible amongst country and grunge musicians whose melodic ruminations center on tragedy, angst and painful relationships. Kurt Cobain comes to mind when he said, “Thank you for the tragedy. I need it for my art.”

Last year the British pop group ironically named, “The Wanted”, brilliantly connected the idea that pain from being unwanted/rejected and searing physical pain were one and the same in their popular song “Lose My Mind”. Here are the lyrics and the video

They say that time
Heals everything
But they don’t know you
And the scars you bring

‘Cos you left a jagged hole
And I can’t stand it anymore

If heartache was a physical pain
I could face it I could face it
But you’re hurting me
From inside of my head
I can’t take it I can’t take it

I’m gonna lose my mind
I’m gonna lose my mind

I’d erase my thoughts
If only I knew how
Fill my head with white noise
If it would drown you out
Kill the sound

If heartache was a physical pain
I could face it I could face it

But you’re hurting me
From inside of my head
I can’t take it I can’t take it

I’m gonna lose my mind
I’m gonna lose my mind

And I’d rather be crazy
I’d rather go insane
Than having you stalk
My every thought
Then having you here inside my heart

If heartache was a physical pain
I could face it I could face it
But you’re hurting me
From inside of my head
I can’t take it I can’t take it

I’m gonna lose my mind
I’m gonna lose my mind

NEUROPEDAGOGY: WHAT MONKEY NEURONS CAN TEACH US ABOUT HOW STUDENTS LEARN

NEUROPEDAGOGY: WHAT MONKEY NEURONS CAN TEACH US ABOUT HOW STUDENTS LEARN

Don Cooper, Professor, Institute for Behavioral Genetics

Our brain’s short-term memory system has been likened to the rewritable
RAM memory of a computer. To perform normal functions, we need the ability
to transiently store, quickly and reliably, large amounts of data, but
only a small amount of this needs to be retained in the longer term.
Scientists have spent decades working out which parts of the brain are
responsible for this memory buffer system, and how neural networks manage
this feat. Given the wealth of detailed information gathered from
neuroscience we are now at a point where we can begin to design pedagogies
that capitalize on the learning and memory models developed from
neuroscience. Professor Cooper will discuss what neuroscience has to say
about attention and learning at the neuronal level and how we can design a
“neuropedagogical” approach to promote learning.

Google glimpses into the mind of God using a Rubik’s cube

What do you get when you give a team of international Rubik’s cube nerds access to Google’s most powerful computers? The answer is 20… and it is a number that previously only God knew. Google’s computers prove that Rubik’s Cube puzzle can always be solved in 20 moves or less. Nerdy Rubik’s researchers claim, “One may suppose God would use a much more efficient algorithm, one that always uses the shortest sequence of moves; this is known as God’s Algorithm. The number of moves this algorithm would take in the worst case is called God’s Number. At long last, God’s Number has been shown to be 20.”

Google’s motto is “Don’t be evil” and now they have proven to have divine insight, but I am not sure the researchers interpretation of God’s nature is accurate. Knowing what we know about the nature of God, since when does God solve problems in the most efficient and elegant manner (the Great Flood notwithstanding), after all God is eternal and doesn’t need to be efficient. Natural selection, the driver underlying the theory of evolution, is a perfect example of the unbiased and patient approach that is more consistent with the nature of God. One wonders how many iterations it would take to arrive at 20 moves using a “natural selection-like” random move-and-learn approach. Using this approach all Rubik’s cube solutions should converge on 20 given enough iterations and memory of prior successful attempts.