Modularity of the mGlu5 receptor explored

Modularity of the mGlu5 receptor explored with Scientifica's SliceMaster system confirming possible therapeutic route for enhancing learning and memory.

Researchers at the Boehringer Ingelheim Pharma GmbH & Co have used Scientifica's SliceMaster multi-slice recording system to help expose the complex role of mGlu5 receptors in early and late hippocampal LTP. The semi-automated system, combined with NPI's extracellular amplifiers, was the perfect system for recording field excitatory postsynaptic potentials (fEPSPs) within multiple CA1 hippocampal slices.

A great deal of work has already been carried out to explore the intricate role mGlu5 receptors play in early and late LTP, and subsequent learning and memory. In the past conflicting results have been reported about the modular nature of the receptors and this could be accounted for by varying experimental conditions creating an unlevel playing field for comparing results between studies.

Therefore Kroker et al conducted a study which involved "two [different] stimulation protocols with otherwise identical conditions" to reveal the modular nature of mGlu5 receptor's role in LTP. It was crucial for the researchers to create and maintain conditions under which only one variable was changing, Scientifica's SliceMaster system provided the ideal platform for this.

The customised system they used consisted of three temperature-controlled brain slice chambers, each with one stimulation electrode, one recording electrode and a camera system.

Two distinct protocols were used to determine the duration and protein-synthesis dependency of early and late LTP. Weak high frequency stimulation (20 stimuli at 100Hz) was used to induce early LTP and repeated strong high frequency stimulation (3 times 100 stimuli at 100 Hz with 5 min interval) was used to induce late LTP. They postulated that early LTP relies on post-translational modifications of pre-existing proteins whereas late LTP is dependent on protein-synthesis.

They used NMDA receptor antagonist MK-801 and L-type calcium channel blocker nifedipine to determine early LTP to be dependent on NMDA receptors only, whereas late LTP was dependent on NMDA receptors and L-type voltage dependent calcium channels (L-DVCCs) in equal parts. They also corroborated previous findings that highlighted mGlu5 receptor's facilitatory role for late LTP with the use of the positive allosteric modulator ADX-47273. They concluded from this that therapeutic use of drugs to enhance mGlu5 receptor activation may boost the late LTP but not protein synthesis independent early LTP.

Kroker et al have provided an excellent study of the physiological role and therapeutic potential of mGlu5 receptors for treatment of specific neurological disorders; creating a clear and repeatable platform for further studies in this area.

Katja S. Kroker, Georg Rast, Holger Rosenbrock Differential effect of the mGlu5 receptor positive allosteric modulator ADC-47273 on early and late hippocampal LTP Neuropharmacology 60 (2011) 707-714