GENETICS OF TIMING

A Genetics Approach to the Interval Timing Mechanism

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'Forward genetics has led to major advances in our understanding of the cellular and molecular mechanism of the circadian clock but there is no comparable understanding of the interval timing mechanism, which enables us to estimate durations and intervals between events. This is unfortunate because the ability to anticipate recurring events is essential for an orgranism’s survival. In this project, we propose an investigation of the neurobiological processes underlying interval timing using two approaches. First, we will use a reverse genetics approach to investigate the role of synaptic plasticity in timing. There is increasing evidence that interval timing involves dopamine modulation of cortico-striatal loops. However, no studies have tested whether synaptic plasticity is necessary for this process. We will address this question by testing mice with whole-brain or area-restricted mutations of the CaMKII gene on a timing task. CaMKII is required for plasticity in many areas of the brain, thus the mutation should interfere with temporal estimation if plasticity is involved in this process. Our second strategy follows a forward genetics approach, similar to the one pioneered by Seymour Benzer when he revealed the molecular machinery of the circadian clock. In our case, we will incorporate a timing task in the battery of automated screens used by NeuroBsik, a consortium, of which the Host is a member, engaged in large-scale phenotyping of mutant mice. These mice have random but easily identifiable mutations. This will allow us to discover new genes that are involved in interval timing.'

Introduzione (Teaser)

Timing is crucial for survival as well as being able to function in activities such as sport and music. European researchers are uncovering the molecular secrets of the interval timing mechanism, responsible for very basic instincts up to performance of sophisticated tasks.

Descrizione progetto (Article)

Time is a fundamental dimension of life. Evolution has selected for mechanisms that allow both humans and animals to respond to the time parameters around them. This may mean the difference between survival and success in the animal world.

There are two distinct mechanisms of timing within living organisms. Circadian timing involves events anticipated on a 24 hour basis controlling obvious functions like sleep-wake patterns and appetite. Interval timing on the other hand controls the ability to calculate shorter durations, in the order of seconds to minutes.

%An internal stopwatch estimates timing for activities like ring doves sitting on a nest of eggs when a long absence would mean death for the youngsters before hatching. At the human level, timing in milliseconds is necessary for speech control, playing music and dancing.

The EU-funded project, Genetics of timing aimed to get to the bottom of how these mechanisms work at a molecular level. Researchers worked with mutant strains of mice that have severe memory and learning deficiencies because of the lack of the protein CaMKII.

The molecule CaMKII induces synaptic plasticity in nerve cells. Plasticity is essential so the connections between nerve cells strengthen, which results in learning ability and memory through reinforcement.

Despite their level of forgetfulness, the mutant mice had no problem learning the durations of intervals set up by the scientists that ranged from 3 to 42 seconds. It is therefore unlikely that CaMKII is involved in interval timing.

Project researchers are also investigating the involvement of another signalling protein in the brain, Erk. This is thought to be responsible for plasticity within key areas in the brain and may be involved in interval timing.

The complex chemical secrets of memory and learning functions are being exposed. The investigation of two major pathways involved has many medical applications including memory loss as a result of ageing.