GAERS

Key takeaways

GAERS belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect GAERS to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of GAERS from memory before moving on to harder problems.

Reference excerpt

The GAERS or Genetic Absence Epilepsy Rat from Strasbourg is a recognized animal model of absence epilepsy, a typical childhood form of epilepsy characterized by recurrent loss of contact and concomitant pattern on the electroencephalogram called "spike-and-wave" discharges. It was first characterized in Strasbourg, France, in the 1980s and since then has been used by different international research groups to understand the mechanisms underlying absence seizures and their ontogeny, using different techniques.

History In the 1980s the research group of Marguerite Vergnes at Institut National de la Santé et de la Recherche Médicale (INSERM) in Strasbourg, France, reported the spontaneous occurrence of spike-and-wave discharges (SWD) evocative of absence seizures in Wistar rats during cortical electroencephalographic (EE) recordings. These seizures were recorded on both sides of the brain, lasted about 20 seconds and occurred when the animals were quiet. Importantly, SWDs were always associated with a typical "arrest" of the rats' behavior with twitching of the vibrissae. In addition, drugs used in the clinic to stop absence seizures (ethosuccimide, valproate) suppressed SWDs in these rats, whereas those that aggravate these seizures in patients (carbamazepine, phenytoine), increased rats' seizures.

Development of two strains These initial observations led to the development of two breeding colonies: (i) a fully inbred strain of rats, with 100% of animals displaying the EEG and behavioral characteristics of absence seizures, derived from an outbred Wistar colony and called the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) (ii) a strain of non epileptic control animals selected from the same initial breeding colony of Wistar rats and called the Non Epileptic Control or NEC. Since then, the GAERS has been recognized as a very predictive model for absence epilepsy, along with the WAG/Rij rat model. The colony, initially developed in Strasbourg, is maintained at the University of Grenoble Alpes, under Inserm licence and the supervision of Antoine Depaulis.

Effects of antiepileptic drugs The reactivity of GAERS to antiepileptic drugs is unique since it perfectly matches with the effects of these drugs in patients with typical absence epilepsy The following table summarizes the effects of the different antiepileptic drugs used in the clinic that were tested on GAERS:

Initiation of spike and wave discharges Using different methodologies (EEG, local field potentials, intracellular electrophysiology, functional MRI) it was demonstrated that spike-and-waves discharges are initiated in the somatosensory cortex in GAERS, more precisely in the area that codes for information from the vibrissae (barrel cortex). Using intracellular electrophysiological recordings of the different layers of the somatosensory cortex, it was found that pyramidal cell of the deep layer (L5/6) initiate the spikes

Epileptogenesis In GAERS, absence epilepsy develops during the cortical maturation, i.e., the first 3–4 weeks after birth. Abnormal oscillations are EEG recorded in GAERS at postnatal day (P) 15. They progressively evolve into bonafide Spike-and-wave discharges up to P25-30, simultaneously with an increase of the intrinsic excitability of pyramidal neurons in deep layers as well as an increase of synchronization.

Genetic transmission and chromosomal mapping In GAERS x NEC F1 generation, more than 95% of the animals showed SWDs after six months, suggesting a dominant transmission. Similar SWDs were recorded in males and females, indicating that the transmission is autosomal. Inter-individual variability suggested that the inheritance of SWDs is not due to a single gene locus and/or that environmental effects might play a role. This mode of inheritance was confirmed in F2 (F1 x F1) and backcross (F1 x control) generations. When F2 population was generated by breeding GAERS with Brown Norway rats, a polygenic inheritance of SWD-related phenotypes was shown and three quantitative trait loci were identified that could control different variables of SWDs (e.g., frequency, amplitude, duration). In this study, the age of the animals was found to be a major factor influencing the detection of genetic linkage to the various components of the SWDs. The development of two inbred strains from the same initial colony has appeared as a very powerful tool to study the possible mutations involved in a genetically complex idiopathic epilepsy. A functional mutation in the Cacna1h gene encoding the Cav3.2 low-voltage activated Ca2+ channel, a T-type calcium channel, was found using the two strains. In addition, the effect is due to a gain-of-function splice variant mutation, and is semi-dominant, explaining about 20% of the phenotypic variance in the cross. In heterologous expression studies, it was shown that the GAERS splice variant allele on Cav3.2 conferred faster recovery from channel inactivation and greater charge transference during high-frequency bursts. This is in agreement with a previous study that showed a selective increase in the T-type conductance in GAERS nRT neurons. It is also in line with the role of the low voltage activated Ca2+ channel in thalamic burst firing and genetic data in human patients.

References

Worked examples

Example 1 — a first encounter with GAERS

Start with the simplest possible case. Write down what GAERS claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to GAERS before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about GAERS ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of GAERS

In research: GAERS appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses GAERS in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: GAERS is common in secondary-school and first-year university syllabi. It links to neighbouring topics Animal models, Electroencephalography, Epilepsy, so understanding it makes those chapters shorter.
In everyday life: Look for GAERS outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study GAERS in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what GAERS means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain GAERS out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is GAERS in simple terms?

The GAERS or Genetic Absence Epilepsy Rat from Strasbourg is a recognized animal model of absence epilepsy, a typical childhood form of epilepsy characterized by recurrent loss of contact and concomitant pattern on the electroencephalogram called "spike-and-wave" discharges. It was first characteri…

Why does GAERS matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study GAERS?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on GAERS.