MEA LTP Assay for Alzheimer Treatment Research

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid plaques, neuronal decline, and memory deficits. The Taconic 1349-RD1 mouse model expresses the human APP695 gene with the Swedish mutation (K670N, M671L), which leads to elevated levels of β-amyloid, promoting the formation of significant amyloid plaques in the brain and resulting in neurotoxicity and cognitive impairments. This model is highly relevant for studying APP expression, amyloid plaque formation, neuronal decline, and memory loss associated with AD.

Using multi-electrode array (MEA) technology, we investigated synaptic properties in Taconic 1349-RD1 mice in comparison with wild-type littermates using electrophysiological assays such as Input/Output (IO) curves, paired-pulse facilitation (PPF), and long-term potentiation (LTP).

• Input/Output (IO) curves measure baseline synaptic transmission by plotting the relationship between stimulation intensity and the synaptic response. Deficits in IO curves can reveal reduced synaptic strength, a hallmark of neurodegeneration.
• Paired-pulse facilitation (PPF) evaluates presynaptic function and short-term plasticity by measuring changes in neurotransmitter release following two closely spaced stimuli. This assay provides insight into probability of release and vesicle dynamics.
• Long-term potentiation (LTP) is the indicator of long-term synaptic plasticity, and a fundamental mechanism for learning and memory. Impairments in LTP reflect a failure of neurons to maintain or strengthen synaptic connections, correlating with cognitive decline.

By comparing Taconic 1349-RD1 mice with wild-type littermates, we observed reduced synaptic activity across all these readouts, with more significant impairments in IO curves and LTP. These results have been reproduced and validate the Taconic 1349-RD1 mouse as a reliable model for synaptic dysfunction, providing high translational value for studying neurodegenerative diseases such as AD.

This model has been developed after overnight incubation, enabling the preincubation of test compounds to assess their effects on synaptic plasticity. It represents a powerful tool for drug discovery and therapeutic testing, for the evaluation of novel treatments aimed at restoring synaptic function and plasticity.

Hippocampal fEPSPs recordings

Synaptic activity is assessed by recording field excitatory post-synaptic potentials (fEPSPs) elicited in the CA1 region through electrical stimulation of the Schaffer collateral pathway. Stimulation is applied at the CA3/CA1 border of the Schaffer collaterals, with an intensity set to 40% of the maximum input intensity (Imax), as determined from the input-output (I-O) curve

Input/Output (IO) curves, paired-pulse facilitation (PPF), and long-term potentiation (LTP) are key electrophysiological assays for assessing synaptic function and plasticity. IO curves provide a measure of baseline synaptic transmission, revealing potential deficits in synaptic strength. Paired-pulse facilitation is used to evaluate presynaptic function and short-term plasticity measuring changes in neurotransmitter release, which can indicate alterations in synaptic connectivity or vesicle dynamics. LTP reflects the brain’s ability to strengthen synaptic connections over time, a fundamental process underlying learning and memory.

By comparing Taconic 1349-RD1 mice with wild-type littermates, we observed reduced synaptic activity across all these readouts, with more significant impairments in IO curves and LTP. These results have been reproduced and validate the Taconic 1349-RD1 mouse as a reliable model for synaptic dysfunction, providing high translational value for studying neurodegenerative diseases such as AD.

This model has been developed after overnight incubation, enabling the preincubation of test compounds to assess their effects on synaptic plasticity. It represents a powerful tool for drug discovery and therapeutic testing, for the evaluation of novel treatments aimed at restoring synaptic function and plasticity

Our subject-matter experts

Bruno Buisson

Co-Founder, President & CSO

Bruno BUISSON is a neurophysiologist and neuropharmacologist with over 30 years of experience in research projects both in academic laboratories and pharma/ biotech companies

Romain Teyssie

MEA Engineer

With a Degree in Biological Sciences and a Master’s Degree in Biotechnology, Romain has 14 years of experience leading customer and R&D projects for the MEA laboratory in France

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