Feeds:
Posts
Comments

Archive for the ‘acetylcholine’ Category

Brainstorm
Image by jurvetson via Flickr

pointer to: Computational Models of Basal Ganglia Function where Kenji Doya provides computational explanations for neuromodulators and their role in reinforcement learning. In his words, “Dopamine encodes the temporal difference error — the reward learning signal. Acetylcholine affects learning rate through memory updates of actions and rewards. Noradrenaline controls width or randomness of exploration. Serotonin is implicated in “temporal discounting,” evaluating if a given action is worth the expected reward.”

This type of amazing research provides a pathway to better understand how genes contribute to how the brain “works” as a 3-dimensional biochemical computational machine.

Reblog this post [with Zemanta]

Read Full Post »

OK, there’s not really a “coolest” part of the brain, but, some areas are pretty darn weird & wild.  Consider the cingulate cortex (shown here).  Electrical stimulation of the pACC region in humans can produce overwhelming fear – even a feeling that death is imminent – while stimulation of white matter tracts adjacent to area 25 can relieve treatment resistent depression. Activity in the MCC region is often associated – not with emotion – but with motor planning and selection of actions.  Stimulation of this area evoked the feeling of “I felt something, as though I was going to leave.” Interestingly, this region also contains a unique type of large neuron known as a von Economo cell,  found in humans and Bonobo chimpanzees, but not other primate species – leading some to speculate that this area must contribute to something that makes us uniquely human.  The PCC and RSC regions seem to be involved in how your brain computes where you are in 3-dimensional space, since activity in the PCC rises when participants mentally navigate pathways and routes of travel or assess the “self-relevance” of sensory stimuli, while lesions in RSC lead to topographic disorientation.  Whew, that’s a lot of functionality !  Indeed, with so many functions, its not surprising that this region is often linked to mental illness of all sorts.  In schizophrenia, for example, patients have difficulty controlling their actions (MCC regions have been implicated) as well as their emotions (ACC regions have been implicated) and maintaining a coherent sense of “self” (PCC & RSC regions have also been implicated).

Since we know that this brain region is implicated in mental illness and we know that mental illness arises – in part – due to genetic risk, it is of interest to begin to understand how genetic factors might relate to the development of structure, connectivity and function of the 4 sub-regions of the cingulate cortex.  With this in mind, it was great to see a recent paper from Brent Vogt and colleagues at the Cingulum Neurosciences Institute [doi: 10.1002/hbm.20667] which has begun to examine differential gene expression in these 4 subregions !  They examined the expression of an array of neurotransmitter receptors (at the protein level actually) and asked whether the expression of the receptors was able to differentiate (as lesions, activity and architectonics do) the 4 subregions.  In a word – yes – with the ACC region showing highest AMPA receptor expression and lowest GABA-A receptor expression.  This was very different from the MCC region which had the lowest AMPA receptor expression while PCC had the highest cholinergic M1 receptor expression.

This seems a great foundation for future studies that will continue to dissect the many interconnected – yet separable – functions of the cingulate cortex.  The “holy grail” of which might be to understand the evolutionary origins of the von Economo cells which are unique to our human lineage.  The genome encodes the story – we just need to learn to read it aloud.

Reblog this post [with Zemanta]

Read Full Post »

California Quail

Image by Len Blumin via Flickr

Am just working up a review on the genetic regulation of the noradrenergic system and stumbled across a collection of papers from ye olde 1980’s. A scientist named Nicole Le Douarin has a series of papers performing a surgical switcheroo of neural tube & neural crest cells from the quail into the chick.  Apparently, the cells survive and differentiate into mature structures and (because the quail cells were distinguishable by Feulgen stain) were a great way to study the effects of “genes vs. environment” on the development of specific cell types. Noradrenergic cells, it turns out can be induced to express cholinergic proteins in response to external cues for example. Interestingly, the chicks born with quail transplants crowed like quail, rather than chicks, demonstrating “the first demonstration of cross-species behavioral transfer brought about by neuronal transplantation.” Balaban et al., Science magazine (1988) vol 241, page 1339.

Reblog this post [with Zemanta]

Read Full Post »

It has been reported that cigarettes can impart some calm and clarity from racing thoughts and mental fog. Patients with schizophrenia, who often experience cognitive disorganization, are 2-4 times more likely than the general population to smoke, and also seem to prefer stronger brands of cigarettes. This is not surprising since nicotine can raise levels of dopamine indirectly via stimulation of alpha4/beta2 high affinity nicotinic acetyl choline receptors (nAChR) expressed widely in the parietal cortex of the human brain. In an open access article entitled, “Association of attentional network function with exon 5 variations of the CHRNA4 gene“, Georg Winterer and colleagues demostrate that individuals who vary in a synonymous G/A variant (rs1044396) in the CHRNA4 gene – an snp which has previously been associated with nicotine dependence – show differential brain activity in the parietal cortex. When asked to remain alert and respond to rare visual “oddball” stimuli (visual oddball detection task), subjects with the AA genotype showed robust brain activity in the parietal cortex while subjects with the GG genotype showed very little change in activity. This finding reveals where in the brain – circuits connecting to the parietal cortex – may be especially important in mediating self-medication and even in the management of side-effects in psychiatric pharmacotherapy. Although rs1044396 is not measured in my 23andMe profile, the neighboring rs3787138 showing tight LD is measured and reveals that I am a boring, middle of the road heterozygote. As such, I do admit that I could use some mind-clearing relief from time to time – but, the yellow teeth are not quite worth it.

Reblog this post [with Zemanta]

Read Full Post »

Varian 4T fMRI, part of the Brain Imaging Cent...Image via Wikipedia Among complex biological datasets, human genomic and functional imaging of the brain are right up there with the most fearsome wild & hairy beasts. Initial attempts to begin to tame the pair of these beasts by cross-relating the two forms of data have employed highly focused, hypothesis-testing strategies – for good reason – any exploratory association study would require a prohibitively large subject population. Liu and colleagues, in their paper, “Combining fMRI and SNP data to investigate connections between brain function and genetics using parallel ICA(DOI) provide a new statistical approach to parsing out meaningful neuroanatomical and genetic components from such complex datasets. The authors record brain activity data while subjects attempt to pick out auditory oddball sounds (beep-beep-beep-beep-beep-boop-beep-beep-). As reported, an analysis of the MRI data and a SNP array consisting of 384 SNPs from 222 genes revealed 10 SNPs that were associated with specific patterns of brain activity. Several SNPs were identified (rs3087454 and rs1355920 are located in the nicotinic acetylcholine receptor-7 (CHRNA7) subunit, rs7520974 is located in the muscarininc acetylcholine receptor-3 (CHRM3) subunit while rs885834 is located in the choline acetyl transferase (CHAT) gene) that would explain the known role of acetylcholine in parietal lobe function, a brain region commonly activated in auditory oddball perception tasks. The method – far beyond this author’s sophistication – nevertheless, seems to output data that is well supported by other forms of converging evidence.

Reblog this post [with Zemanta]

Read Full Post »

In a recent free and open BMC report on gene expression in non-smokers vs. current smokers vs. quitters, Chari and colleagues identify a class of genes whose expression “appears to be permanently altered despite prolonged smoking cessation.” Frighteningly, a number of genes encoding DNA repair enzymes are irreversibly altered … definitely not good to mutagenize your genome and then knock out the repairman. Worse yet, another gene that popped up was calcium binding tyrosine-(Y) phosphorylation regulated (CABYR) a gene that is found in the sperm flagellum, lung and brain (these are all tissues with cells that are rich in microtubules and dynein motors – so perhaps CABYR plays a smoking-related role in the lung in ciliary clearance of mucous). Wait a minute, did someone say sperm cell ? Ouch – no more cigarettes please. Although, the effects of smoking on CABYR expression were reversible, I don’t need a direct mutagenic hit there to make me wince, just thinking about that is enough.

Reblog this post [with Zemanta]

Read Full Post »

A 21 mg patch applied to the left arm
Image via Wikipedia

Uhl and colleagues present a genome-wide search for SNPs that distinguish smokers (nicotine dependence) – and perhaps more importantly – successful smoking quitters, in their recent article in the free and open-access journal BioMed Central. As pointed out in the article, this work is a step closer to personalized “efforts to match vulnerable individuals with the prevention and treatment strategies most likely to work for them.” A set of genetic variants that distinguish nicotine dependence from a control population with no personal history of smoking or substance abuse was identified and a novel set of variants that distinguish folks who’ve had success after using the patch and other self-help methods are exciting new tools that were produced by the study.

Reblog this post [with Zemanta]

Read Full Post »