Brain somatostatin: receptor-coupled transducing mechanisms and role in cognitive functions

In recent years there has been an increased interest in understanding the role of somatostatin in the brain. This review summarizes the current knowledge of the anatomical distribution of somatostatin and its receptors, the receptor-coupling mechanisms and the somatostatinergic modulation of cognitive functions. Somatostatin is also highly concentrated in the extra-hypothalamic areas of the brain, including the frontal and parietal cortex and the hippocampus. At these locations somatostatin may play a fundamental role in the modulation of cognitive functions. Activation of somatostatin receptors in the brain results in an inhibition of adenylate cyclase enzyme activity, reduction in intracellular Ca2+ levels and hypopolarization of cells by inducing outward K+ currents. Biological studies on the effects of increased brain somatostatin showed a facilitation in learning behavioural tasks, while brain somatostatin depletion by cysteamine caused memory loss. These observations, along with the severe somatostatinergic neurotransmission impairment demonstrated in Alzheimer's patients, strongly suggest a fundamental role for somatostatin in the modulation of cognitive functions.