This article concerns attention, attention-based learning, and D4 dopamine receptors.
The membrane surrounding your cell, the plasma or cell membrane, is represented here by a three-dimensional fluid mosaic. The cell membrane is composed of a bi-lipid layer, a double layer of lipid or fat, which has a head at one end. The lipid is actually phospholipid.
Nerve cells have a phospholipid cell membrane. In this depiction, the head is represented by the red, green, purple and lime green rounded structures. Anyone who has listened to the Tuesday night calls has heard me talk about phospholipids at length. Phosphatidyl serine complex, that important shortcut support everybody starts out on, is a complex of the same phospholipids that make up the nerve cell wall.
Receptor sites are positioned in the cell membrane. They are represented by pink lobed molecules with antenna-like structures projecting out of them. The antenna-like structures grab the appropriate molecule for the type of receptor involved and transport it into the cell.
The cell membrane must be fluid…. It can’t be rigid. If it is too rigid, the molecules in the membrane can’t move or function properly. They need to be able to move in order to signal appropriately.
Some receptors function by totally inverting into the cell. They invert and pull the substance into the cell by doing so. You cannot have a stiff, inflexible cell membrane and do this effectively. That is what is wrong with trans fats: they are too stiff.
The receptor I am focusing on today is the D4 dopamine receptor. Dopamine is the neurotransmitter responsible for attention, motivation, and reward-motivated behavior. It is an extraordinarily important neurotransmitter because it is the predominant neurotransmitter in your pre-frontal cortex.
Cognitive behavior is processed in your pre-frontal cortex. It is where your executive function resides. It’s the brain power you use to cross the street, the mental apparatus that you need to make decisions. It’s the seat of your personality, the home of all the characteristics that make you you.
The D4 dopamine receptor is responsible for attention and attention-initiated learning. It operates by inverting into the cell. A very fluid cell membrane is necessary to do this.
Methylation of the heads of the phospholipid layers, called phospholipid methylation, or PLM, increases the fluidity of the cell membrane. Dopamine activation of the D4 receptor initiates a cycle of phospholipid methylation.
On the left side, there is no phospholipid methylation. There are no methyl groups between the heads of the molecules in the membrane.
When there is space made by the methyl groups between the phospholipid heads, there is more room for the receptors to be able to move and function. It is a more fluid membrane. The protein receptor will be able to move around better and will be able to signal and react with other proteins more easily.
Inadequate methylation negatively impacts your ability to attend and learn. The dopamine receptor needs to be able to reconfigure itself. It needs to be able to invert itself into the cell and then come back out again. It is not able to do that if the membrane is too solid.
Phospholipid methylation, the addition of a methyl group to phospholipids, reduces the packing density of the membrane and enhances the activity of embedded, integral membrane proteins like the D4 receptor.
The activity of the D4 receptor mediated phospholipid methylation cycle is affected by the availability of 5 methyl tetrahydrofolate (5 MTHF). When the level of 5 MTHF is decreased, it becomes a limiting factor. The receptors sit waiting for a new methyl group to start the activation. This greatly reduces the impact of any dopamine present. Even very high amounts of dopamine that may be present will not activate the receptor if there is too little 5 MTHF.
What determines 5 MTHF availability? The function of the MTHFR C677T mediated enzyme is critical for an adequate supply of 5MTHF. MTHFR 3 is even a more profound down-regulation of enzyme activity than MTHFR C677T.
Recent work suggests that supporting with methylfolate may be a help in offsetting depression for those who are resistant to SSRI therapy. However, the methylation cycle needs to be supported in a more general way, rather than simply adding methylfolate.
Also, we are talking here about appropriate dosing of 5 MTHF for your personal genetics, not the massive amounts of 5 MTHF that is sometimes recommended.
You need to know the status of all of the genes encoding for the enzymes in your methyl group-producing pathways, so you can bypass any problem genetics and be sure you have the methyl groups you need to perform all of the important functions that involve methyl groups.