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Focus Paper

Accardi MV, Brown PM, Miraucourt LS, Orser BA, Bowie D

α6-Containing GABAA Receptors Are the Principal Mediators of Inhibitory Synapse Strengthening by Insulin in Cerebellar Granule Cells

J Neurosci. 2015 Jul 1;35(26):9676-88. doi: 10.1523/JNEUROSCI.0513-15.2015. PubMed Link

Insulin has long been known as the hormone which controls the body’s sugar levels: humans who lack or are insensitive to insulin develop diabetes. Although insulin is also made and released in the brain, its effects there have remained unclear. In this paper we report a new role for this metabolic hormone. Insulin controls the activity of the brain’s ‘brakes’, which are called inhibitory GABA-A receptors. Insulin prevents the brain from getting overexcited by calling upon a subtype of GABA-A receptors - a discovery which may lead to new treatments for epilepsy and other central nervous system conditions.

GABA-A receptors are targeted by many psychoactive drugs such as benzodiazepines (e.g. valium) which are used to treat anxiety, induce anesthesia in surgery and relieve chronic pain. Although beneficial, these drugs often have unwanted side-effects. We found that regulating the brain's own chemistry using insulin brings about the same beneficial effect of these drugs, suggesting new routes for drug therapies that may have fewer side-effects.