Dynamic Neuroplasticity after Human Prefrontal Cortex Damage.


ResearchBlogging.org In this article, the authors focused on the effects of a unilateral lesion within the prefrontal cortex. Human vision works upon a rather backwards system. Information from the left side of each eye moves toward the left occipital lobe to be analyzed. The right follows an identical pattern.

So essentially, two sides of the eyeball swap information between hemispheres. From here, the information is sent forward along the current hemisphere to be analyzed by the prefrontal cortex (PFC).Because what else would you expect from the brain? In a nutshell, the left and right fields of vision (of a single eye) are interpreted by different halves of the brain. This is where the problems begin to arise. If the lesion occupies the left PFC, what happens to that information? Does it simply get left unanalyzed and you lose that field in each eye?

In a static environment you could assume that the side affected by the lesion would lose greater processing for that side of the brain. However, if the brain were dynamic and could re-route the circuit, information from that field could have the potential to return. It seems that’s just what occurs but with a small cost. The information destined for the left PFC follows the tradition route back to the prefrontal cortex but stops short, makes a pass through the corpus callosum,  and arrives at the contralateral prefrontal cortex (right side). The right prefrontal cortex actually picks up the slack left from the damaged area. However, as this seems almost too good to be true, this is not the case under all conditions. When an object is detected in the affected field compensation occurs. Yet, when objects are present to both fields simultaneously the right PFC solely analyzes the information from the right field. In other words, the right PFC picks up the slack so long as it has no incoming information itself.

The brain undergoes this change after repeated exposure to left field stimuli on a trial-by-trial basis. While the left PFC never fully recovers, this example shows a rather interesting compensation mechanism that can be achieved plastically. Although the paper never actually discussed this, I can’t help but wonder about the underlying cellular changes associated with this feat. Currently my assumption would just be an increase in synapses (synaptogenesis) favoring the re-wiring across the corpus callosum and to the contralateral cortex. But that’s just my guess. If anyone has any thoughts to the contrary I would certainly be willing to entertain them.

Voytek, B., Davis, M., Yago, E., Barceló, F., Vogel, E., & Knight, R. (2010). Dynamic Neuroplasticity after Human Prefrontal Cortex Damage Neuron, 68 (3), 401-408 DOI: 10.1016/j.neuron.2010.09.018 

*UPDATE*: I figured using ResearchBlogger would be more efficient.


Hiatus.


So if you haven’t noticed, there has been a sizable gap in between posts. Whoops. Vacation and plans for world domination (not kidding) have consumed a fair chunk of my time. Most of my attention at the moment is directed at my Senior Seminar. Currently it’s dealing with Neuroplasticity and the Effects of Constraint Induced Therapy on Stroke Patients. So if anyone knows Dr. Edward Taub on a  first name basis, put in a good word for me. Pretty please?


I Think, Therefore I Am


This was a piece written for our Developmental Biology final. I wrote this with the intention of pushing a radical, controversial concept that I had never seen before. This article does not necessarily reflect my own views. This was merely an assignment I had a bit of evil fun with. Enjoy!

–Rev.Frost

Continue reading


Innate Immunity: So Nice, They Made It Twice


People often use the phrase “do not reinvent the wheel” to describe using an existing method towards a new task rather than creating one anew. Evolution tends to follow a similar philosophy. Many changes utilize genetic toolkits that have long been present, tucked away in the genome of the organism. Sometimes these toolkits have already been used repeatedly for various traits. The common fruit fly (Drosophila melanogaster), a model test subject for over a century, has been scrutinized in remarkable detail to gain an understanding of molecular interactions and evolution. When researchers discovered the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in mammals that functioned remarkably similar to the Toll pathway in Drosophila it was assumed that the immunological pathways were homologous (e.g. using the same toolkit).

The NF-kB pathway establishes its importance due to its swift reaction time. Most transcription factors are synthesized as needed. Building a protein from scratch then applying it where

Figure 1: Contrasting transcription pathways between Drosophila and Mammals

needed takes a fair amount of time. Sometimes, like during a pathogenic invasion, the cell cannot survive long enough to produce these proteins. In the immune system these proteins can be constructed preemptively, bound, and inhibited in the cytosol for future use. The NF-kB pathway activates these stored proteins by cleaving the inhibiting molecule and thus allowing the transcription factor, NF-kB, to enter the nucleus. The Toll pathway operates, essentially, in the same fashion as NF-kB (Figure 1). However, Drosophila uses completely different proteins to ultimately provoke a similar immune response with Dorsal-related immunity factor (Dif ).

The Toll pathway plays another, yet significant role only found in Drosophila. After the egg is

Figure 2: The Toll-Dorsal Pathway in Drosophila melanogaster

fertilized it lays the foundation for the rest of development, ventral and dorsal (down and up). Upon fertilization, the ligand Spätzle (SPZ) is distributed across the perivitelline membrane (Figure 2a). From here, SPZ binds to the Toll receptors of cells maternally designated to become ventral. The Toll receptors set in motion a cascade that phosphorylates CACT (the inhibitor) which allows the transcription factor to promote the production of the protein Dorsal (Figure 2b).

These pathways were initially thought to have arisen from a common ancestor to both Drosophila and mammals. However, it seems this is only partially correct. Genomic research opened up new, previously unexplored areas to consider. This pathway did, initially, form in a Eumetazoan ancestor. This pathway was markedly underdeveloped and only contained a few components. When the bilateral lineage diverged into deuterostomes and protostomes the common pathway ended. From here, both NF-kB and Toll evolved independently through gene duplication.

These diverse differences between pathways give great insight to the evolutionary history of the circuit itself. In order to have diverged so far in composition yet retain similar function suggests the ancestral pathway to have been particularly modular. In other words, the ancestral pathway was constructed using multiple pieces (modules). This setup allows individual modules to be modified over time without removing the core process of the system. Drosophila slowly modified this pathway to affect larval development by introducing Dorsal and SPZ into the circuit. As a result, Drosophila is able to use a single genetic circuit for dual regulation.

In Biology, nothing is ever as simple as it appears to be. The subjects could range from immune response pathways and developmental regulation to simple autosomal point mutations, but more research is always needed. The NF-kB pathway was thought to be well known until just recently, yet new information radically altered our understanding of it. With additional research, who knows what we could uncover next?

Belvin, M. P., Anderson, K. V., 1996. A CONSERVED SIGNALING PATHWAY: The Drosophila Toll-Dorsal Pathway. Annual Review Cell Developmental Biology. 12, 396-416.

Lemaitre, B., 2004. The road to Toll. Nature Reviews Immunology. 4, 521-527.

Leulier, F., Lemaitre, B., 2008. Toll-like receptors — taking an evolutionary approach. Nature Reviews Genetics. 9, 165-178.

Waterhouse, R. M., Kriventseva, E. V., Meister, S., Xi, Z., Alvarez, K. S., Bartholomay, L. C., Barillas-Mury, C., Bian, G., Blandin, S., Christensen, B. M., Dong, Y., Jiang, H., Kanost, M. R., Koutsos, A. C., Levashina, E. A., Li, J., Ligoxygakis, P., MacCallum, R. M., Mayhew, G. F., Mendes, A., Michel, K., Osta, M. A., Paskewitz, S., Shin, S. W., Vlachou, D., Wang, L., Wei, W., Zheng, L., Zou, Z., Severson, D. W., Raikhel, A. S., Kafatos, F. C., Dimopoulos, G., Zdobnov, E. M., Christophides, G. K., 2007. Evolutionary Dynamics of Immune-Related Genes and Pathways in Disease-Vector Mosquitoes. Science. 316, 1738-1743.


Trisomy…22?


Many people are familiar with Trisomy 21 in humans. Commonly known as Down Syndrome, Trisomy 21 severely affects human development via complex gene and environmental interactions. Genetically speaking, is this condition novel to humans? Or can this be seen in other primates? Most of the “great apes” contain 24 pairs of chromosomes, humans being the exception with 23. When compared, the two karyotypes  look strikingly similar. The only vast difference occurring on chromosome 2. From the diagram below, the human chromosome 21 and the great ape chromosome 22 look remarkably similar. Documented cases of Trisomy 22 in chimpanzees have been seen as far back as 1969. With the additional #22, symptoms parallel to Down Syndrome appeared. Continue reading


Exams, Planes, and Delays!


It would seem that I have accidentally taken a brief hiatus from my blogging duties! Allow me to explain my absence.

This week marked our first developmental biology exam. As it was a take-home essay, it is needless to say this consumed every moment of spare time available. Fortunately it seems I was not the only student who shirked their blogging duties as only one of seven students posted on time! Strength in numbers, right?

As my professor jetted off halfway around the world I relocated to a much warmer climate, Phoenix. There is no feeling like being in a prairie in the morning then landing in a desert to be greeted by an In-N-Out Double double: animal style.

But never fear! I believe I am still required an additional post to appease the almighty PZ (calling him almighty gets me an A, right?). So here’s a spoiler of the next post to come: primates and faulty cohesin.

On one last note, I was informed to inform you (to inform others) that this person is Not a doctor. Good job, Rhys Morgan. Keep slaying them.


Circadian Rhythm and Synapse Activity in Zebrafish


The other day I found an article that seemed all too perfect. Development. Neurology. Zebrafish. For those of you who don’t know, these little fishies are not only PZ’s specialty but are also currently taking over our lab (You will be missed, fishies in tank #3).

In zebrafish, the sleep-wake cycle is regulated by hypocretin neurons (HCRT). These neurons also play a major role in mammals as well and if damaged can lead to narcolepsy. The researchers labeled these neurons in zebrafish with a presynaptic marker synaptophysin (SYP) attached to a fluorescent dye. Now the researchers can look at activity across the span of a day to visually quantify changes in baseline function or artificially produced by various conditions (e.g. sleep deprivation). So,  they irritated fish for several hours after normal sleeping time until the fish were nice and sleep deprived.

The sleep deprived fish showed homeostatic influences on the number of HCRT synapses. Why is this important? The fish showed that upon sleep deprivation more synapse terminals were created  to maintain cellular balance. Yet, simultaneously, the natural circadian rhythm began to decrease the number of synapses from the point of initial sleep deprivation. Homeostatic effects are estimated to be a mere 17% and this result appears only after six hours of deprivation. Essentially, as the day wears on the brain winds up more and more. The circadian rhythm counteracts this by gradually resetting the system back to baseline. A portion of this study showed that as the system tries to reset, sleep deprivation will weakly offset efficacy leading to impairment in memory retainment (and overall cranky fish).

*Professor, I would have gotten that question right but the course workload created homeostatic effects which led to faulty memory retainment!*


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