Category Archives: dopamine

On The Ways That Brains Change

from reference 1

It is well known that nervous system plasticity (the mutable quality of brains) underlies animals’ ability to change their behaviors. However, it has been widely thought that such plasticity consists mostly of changes at synapses, the sites of communication between neurons, or in the intrinsic excitability of individual neurons – how likely a cell is to increase or decrease its voltage or to fire action potentials. New research challenges this view by showing that another type of alteration can be at work: single neurons can change the type of neurotransmitter they release in response to stimulation1.

Specifically, this work addresses tadpole camouflage. Tadpoles can rapidly change (increase or decrease) the amount of pigmentation in their skin in order to blend in with their surroundings. The research I here refer to demonstrates that when frog tadpoles (Xenopus laevis) are stimulated with bright light, the number of dopamine-secreting (dopaminergic) neurons in the animals’ brains increases, allowing them to adapt more rapidly to subsequent exposure to light.

When exposed to just hours of direct light, dark-reared tadpoles responded by doubling the number off dopaminergic neurons within a part of their central nervous system called the suprachiasmatic nucleus (SCN). Furthermore, these new dopaminergic neurons seem to integrate into the existing pathways for changing pigmentation. The authors were able to selectively destroy existing SCN dopaminergic neurons, eliminating the tadpoles ability to change pigment, and then rescue this ability with light exposure.

It remains unclear if this phenomenon is purely a developmental one, operating only prior to adulthood, an important caveat. None the less, the ability to change cell type is an as-yet unexplored form of neural plasticity which will have widespread implications for neuroscience research. Furthermore, this work may have even more direct application to human experience.

In human beings, the malfunction of certain dopamine-mediated signalling cascades (cell-level combinations of molecular interactions) have been implicated in seasonal affective disorder (winter depression). It is also well known that dopamine is intrinsically involved in the rewarding feelings delivered by food, sex and drugs. It may thus simply be the case that a lack of light stimulation leads to a lack of dopaminergic neurons, and thus to fewer episodes of rewarding experience during the winter months.

1. Dulcis D, Spitzer NC. Illumination controls differentiation of dopamine neurons regulating behaviour. Nature 456: 195-201, 2008.

On Rodent Parkinsons

The cover of the journal Brain

Therapies based on stem cells rely heavily on our ability to coax these blank-cellular-slates into taking on specific forms. Stem cells are exciting as possible sources of medicinal therapy because they have the potential to become any type of cell in the body, but in order for their utility to be realized, we must be able to reliably effect their fates. The process of turning a stem cell into a specific cell type is called, logically, differentiation. With the exception of the immune system, the brain has more cell-types than any other organ, not to mention some of the most differentiated (exotic or distinct) types. Thus, many scientists are busily engaged in the activity of deducing molecular algorithms for deterministic control of their cellular end-state.

One disease where there seems to be a clear connection between cell-type-specific disfunction and pathology is Parkinson’s Disease. In this debilitating condition, the afflicted progressively loose motor function due to a lack of stimulation of their motor corticies (the area responsible for directing movement in the human brain) by dopaminergic neurons found in the amygdala (another brain region associated with emotion and reward). Further, it appears to be the case that the reason for this lack of stimulation is simply a lack of production of dopamine by these dopaminergic amygdalar neurons. The cell-type specificity of the disease makes it an an excellent candidate for treatment by replacing the existing hypoactive neurons with newly differentiated stem cell versions of their kind, which should have normal dopamine production abilities.

A recent paper appearing in the journal Brain reports the results of a study in which the researchers have achieved just such a therapeutic cell-type replacement in rats with a “model” of human Parkinson’s disease (ref. 1). They report that motor function was restored by this approach, and further that the longevity of the differentiated cells was related to their restorative efficacy. Further examples of work like this promise to revolutionize the treatment of a host of diseases.

1. Sanchez-Pernaute R, Lee H, Patterson M, Reske-Nielsen C, Yoshizaki T, Sonntag KC, Studer L, Isacson O. (2008) Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson’s disease. Brain.

On Motivating the Anecdotal

I was recently asked the question: “Why do things taste better when they’re free?” While this hardly constitutes a rigorous scientifically testable hypothesis, I thought I’d wax speculative about it for a moment.

The explanation of why some may have this experience lies in the fact that your brain has a unified reward system based on the small molecule dopamine. This system is responsible for many types of associative learning (including classical Conditioning a la Pavlov), and signals rewards to be gained from engaging in various behaviors such as eating, having sex, or doing drugs1. Further, it seems likely that the dopamine system is responsible for making us feel happy about having received monetary returns1.

In the free-food-tastes-better case, this system is double activated. There is a reward for having gotten something for free along with a reward for eating something. However, there is sometimes only one action to assign the reward to: eating. Perhaps when there is no immediate action to be applauded for providing the free-food-prize, the brain simply heaps all the praise on the eating itself, thus resulting in the delightful (and dangerous) experience of the free snack being extra desirable.

1. Caplin, D & Dean M (2008) Dopamine, Reward Prediction Error, and Economics. The Quarterly Journal of Economics. 123(2), 663-701

On Dopamine and Ethics?

It has long been known that the hormone dopamine plays a key role in both addictive and learning behaviors. As with all neurotransmitters, “normal” functioning of these small molecules in the body depends on their receptors, of which there can be several types.

Two papers, published last year in the journal Science, both focus on particular dopamine receptor types, and behaviors associated with them. Work from Jeffrey Dalley’s lab1 uses PET to demonstrate that impulsive rats have significantly lower availability of two dopamine receptor types in a certain brain area, and further, that such impulsivity predicts how effective cocaine is in reinforcing behaviors thatt cause its administration. Meanwhile, experiments conducted by Tilmann Klein2 indicate that people with a certain allele of one type of dopamine receptor are significantly less able to learn a task via negative feedback.

The latter work, however, has implications beyond the nature of learning. This is the first example of a certain type of human behavioral trait about which one can make quantitative predictions through genomic analysis. This trait is one that has the potential to stratify people; categorize them before birth according their potential abilities.

This gene presents the possibility for exactly the sort of genetic profiling that many have predicted with dread. The former work mentioned above carries some of the same baggage, a PET scan based screening of individuals could potentially be done quite early, and it is not hard to imagine the development of genetic screens to forecast “dopamine receptor availability.” An interesting conclusion to the presentation of these ideas would be some exploration of the actual value of being able to learn from negative feedback. Are those less able to learn in this way simply more bold? Fearless? Risk-takers? More creative? Could there be some value in attempting to tailor one’s activities to one’s genetic disposition?

Just as the construction of the atomic bomb raised questions about the ethics of conducting certain types of research in the physical sciences, recent work such as that mentioned here does the same for neuroscience. As it gains widespread interest and makes increasingly strong predictions about human beings and their behaviors, the power of great neuroscientific research must be wielded as gingerly as any.

1. Dalley, JW et al, (2007) Nucleus Accumbens D2/3 Receptors Predict Trait Impulsivity and Cocaine Reinforcement, Science, Vol. 315:1267-1270 | 
DOI: 10.1126/science.1137073

2. Klein, TA et al, (2007) Genetically Determined Differences in Learning from Errors, Science, Vol. 318:1642-1645 |
DOI: 10.1126/science.1145044