CNCR scientists find receptor responsible for attention

16 August 2011

Huib Mansvelder, Sabine Spijker and collaborators published a study in Science, demonstrating which neuronal receptor is responsible for the deterioration of concentration and memory.

These findings will lead to the development of more specific drugs in treatment of Alzheimer’s disease in time.
In one third of the population, concentration and memory decline with age. Different brain systems are involved in this process, including the neuronal acetylcholine receptor acetylcholine in the Prefrontal Cortex (PFC), which regulates attention.
In people who have Alzheimer’s, the acetylcholine cells die.
“We wanted to know in which part of the Prefrontal Cortex acetylcholine works,” said Huib Mansvelder, professor of neurophysiology (NCA, CNCR). “In our research, we have focused on a specific type of acetylcholine receptor, the nicotinic receptor.”

Knock-out mice
To know how acetylcholine regulates attention with the help of nicotinic receptors, the nicotinic receptors were removed in knockout mice. An attention test showed that mice lacking the nicotinic receptors performed worse than mice from the control group.

Following these tests, attention was restored by re-introducing the DNA of nicotinic receptors, using viral technology. This happened in two places of the PFC. With the re-introduction in the prelimbic area of the PFC, the attention performance was back to normal.

Mansvelder: “Our study clearly demonstrates that defined receptors in specific parts of our brains strengthen concentration and attention.”
To apply these findings in human attention and to develop drugs that target these receptors, similar brain regions in humans have to be identified first.

Mansvelder: “Right now, people with Alzheimer’s use drugs that prevent the breakdown of acetylcholine – but in the entire body. As soon as we have identified the exact location of the nicotinic receptors in the appropriate brain areas, we can develop highly specific drugs that work only in those areas. ”

Genetic variations
The development of these specific drugs is further complicated by the fact that there are genetic variations among people that influence the functioning of receptors. Mansvelder: “Every person is different. Therefore, research in mice is not so easily translated to people. It will be at least another ten years before these highly specific drugs will be available. “

Nicotinic Acetylcholine Receptor β2 Subunits in the Medial Prefrontal Cortex Control Attention
Karine Guillem, Bernard Bloem, Rogier B. Poorthuis, Maarten Loos, August B. Smit, Uwe Maskos, Sabine Spijker, Huibert D. Mansvelder
Science 12 August 2011: Vol. 333 no. 6044 pp. 888-891

Summary of the paper: INF_Science_Guillem2011.pdf (166.39 KB)