SK channels could be the missing link between brain state and cognitive function
New findings at the University of Bristol could lead to therapeutic drug developments to treat neurological diseases such as Alzheimer's.
Researchers at Bristol University are delving deeper into the specific mechanisms that underly learning and memory in a bid to gain greater understanding of cognitive function.
Long-term potentiation (LTP) is widely accepted as the fundamental mechanism underlying learning and memory within the brain and is regulated by NMDA receptors. The team at Bristol has been studying, in isolation, the affect of drugs that target acetylcholine receptors and SK channels and their subsequent affect on LTP in the hippocampus. They used whole cell patch clamping techniques to measure the induction of LTP within the cells under different conditions.
Their findings have highlighted the crucial relationship between release of acetylcholine and SK channels. They describe how release of acetylcholine will inhibit SK channels and lead to facilitation of LTP in the hippocampus.
The SK channels' usual function is to restrict the activity of NMDA receptors, so by removing this level of inhibition to NMDA receptors synaptic plasticity is facilitated.
Current drug treatments for diseases such as Alzheimer's focus on enhancing the effects of, already present, acetylcholine in the brain. These new finds suggest a method of treatment by drugs that "mimicks" the effect of acetylcholine at specific receptors.
Although these are early stages of research this could prove to be an exciting area of development, with limitless possibilities in the future.
Lead researcher Dr Jack Mellor, from the University of Bristol's Medical School, said:
"These findings are not going to revolutionise the treatment of Alzheimer's disease or other forms of cognitive impairment overnight. However, national and international funding bodies have recently made research into aging and dementia a top priority so we expect many more advances in our understanding of the mechanisms underlying learning and memory in both health and disease."
Paper details: Facilitation of Long-Term Potentiation by Muscarinic M1 Receptors Is Mediated by Inhibition of SK Channels.
Neuron, Volume 68, Issue 5, 948-963, 9 December 2010
Authors
Katherine A. Buchanan, Milos M. Petrovic, Sophie E.L. Chamberlain, Neil V. Marrion, Jack R. Mellor
Full details available at:
http://www.bristol.ac.uk/news/2010/7354.html
(The research team involved the University of Bristol's MRC Centre for Synaptic Plasticity and the Division of Neuroscience in the School of Physiology & Pharmacology, part of the Bristol Neuroscience network. This work was supported by the Wellcome Trust, MRC, BBSRC, GSK and Marie Curie Fellowship)
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