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Posts Tagged ‘Dopamine’

Holiday time is full of all things delicious and fattening. Should I have a little chocolate now, or wait till later and have a bigger dessert ? Of course, this is not a real forced choice (in my case, the answer too often seems – alas – “I’ll have both!”), but there are many times in life when we are forced to decide between ‘a little now’ or ‘more later’. Sometimes, its clear that the extra $20 in your pocket now would be better utilized later on, after a few years of compound interest. Other times, its not so clear. Consider the recent ruling by the Equal Employment Opportunity Commission, which allows employers to drop retirees’ health coverage once they turn 65 and become eligible for Medicare. Do I save my resources now to provide for my geezerdom healthcare spending, or do I enjoy (spend) my resources now while I’m young and able ? How do I make these decisions ? How does my life experience and genome interact to influence the brain systems that support these computations ? Boettiger and company provide some insight to these questions in their paper, “Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158Val/Val Genotype(DOI). The authors utilize an assay that measures a subject’s preference for rewards now or later and use functional brain imaging to seek out brain regions where activity is correlated to preferences for immediate rewards. Dopamine rich brain regions such as the posterior parietal cortex, dorsal prefrontal cortex and rostral parahippocampal gyrus showed (+) correlations while the lateral orbitofrontal cortex showed a (-) correlation. Variation in the dopaminergic enzyme COMT at the rs165688 SNP also showed a correlation with preferences for immediate reward as well as with brain activation. The authors’ results suggest that improving one’s ability to weigh long-term outcomes is a likely therapeutic avenue for helping impulsive folks (like me) optimize our resource allocation. I have not yet had my genome deCODEd or Google-ed, but strongly suspect I am a valine/valine homozygote.

Indeed it seems I am a GG (Valine/Valine) at this site according to 23andMe !

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B.F.Image via Wikipedia

I’m not sure what Skinner would have thought, but its clear that, nowadays, mechanisms of behavior can be understood in terms of dynamic changes in neural systems and, furthermore, that individual differences in these neural dynamics are heavily regulated by genetic variation. Consider the recent paper by Lobo et al., “Genetic control of instrumental conditioning by striatopallidal neuron–specific S1P receptor Gpr6(DOI). The authors use molecular genetics to seek out and find key genetic regulators of a specific and fundamental form of learning – operant or instrumental conditioning, pioneered by B.F. Skinner – wherein an individual performs an act and, afterwards, receives (+ or -) reinforcing feedback. This type of learning is distinct from classical conditioning where, for example, Pavlov’s dogs heard a bell before dinner and eventually began to salivate at the sound of the bell. In classical conditioning, the cue comes before the target, whereas in operant conditioning, the feedback comes after the target. Interestingly, the brain uses very different neural systems to process these different temporal contingencies and Lobo and company dive straight into the specific neural circuits – striatopallidal medium spiny neurons – to identify genes that are differentially expressed in these cells as compared to other neurons and, in particular, striatonigral medium spiny neurons. The GPR6 gene was found to be the 6th most differentially expressed gene in these cells and resultant knockout mice, when placed in an operant chamber, were much faster than control animals in learning the bar press association with a sugar pellet reward. The expression of GPR6 in striatopallidal cells predicts that they should have a normal function in inhibiting or slowing down such associations, so it makes sense that the GPR6 knockout animals are faster to learn these associations. This is one of the first genes whose function seems specifcially linked to a core cognitive process – Skinner might have been impressed after reading the paper.

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Deep-fried onion rings arranged in a line on a...Image via Wikipedia To go out tonight or stay home? Hillary or Barack? Curly fries or onion rings? How do I make these important choices and why will others decide differently? Although there are many reasons for not stressing-out and over-thinking one’s decisions (except for really important choices like curly fry vs. onion ring), it turns out that variation in your genome, in particular, 3 dopaminergic genes (DARPP-32, DRD2 and COMT: rs907094, rs1800496, rs4680) are influencing your tendency to ‘go for it’ or not to go for it. Frank and colleagues, in their paper, “Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning“, give an in-depth treatment of the neurobiology underlying decision making and reinforcement learning. After carefully reviewing the basic biology of dopaminergic synapses and selecting 3 candidate genetic variants, they find that each is associated with an independent aspect of decision making in a learning paradigm. The paper is an excellent example of how genetic variation can be linked to specific neural processes. Now bring on the curly fries – no wait – the onion rings.

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