by Thomas Stroh, PhD

Nerve cells, or neurons, talk to each other at specialized junctions called synapses. There are perhaps 100 trillion synapses in the human brain, 1,000 or so for each of the brain's 100 billion neurons. When a "presynaptic" neuron wants to talk to its "postsynaptic" partner, it releases chemicals called neurotransmitters which bind to and activate proteins called neurotransmitter receptors on the surface of postsynaptic cell (see the figure below). Once the receptors are activated, they initiate electrical and chemical events in the postsynaptic cell. In this way, information is passed from one cell to another.

One of the most important families of neurotransmitter receptors are called G protein-coupled receptors, or GPCRs. There are many types of GPCRs, found not only in the brain, but also throughout the rest of the nervous system and in other tissues as well. These receptors are especially interesting because one of their jobs is to influence subjective feelings such as mood, pleasure and attention. In fact, many psychiatric drugs, such as the antidepressant Prozac, as well as most drugs of abuse act either directly or indirectly on GPRCs. Thus, understanding how these receptors work has important scientific and therapeutic implications.

Thomas Stroh's laboratory at the Montréal Neurological Institute studies GPCRs that are activated by a neuropeptide called somatostatin. (Neuropeptides are soluble molecules, comprised of short strings of amino acids. They are released by neurons and other cells, and include such familiar substances as β-endorphin, oxytocin and insulin.) Somatostatin plays a critical role in controlling the release of hormones from the pituitary gland, the body's master gland, located at the base of the brain. It also fine-tunes other neurotransmitter and hormonal systems. Somatostatin exerts its physiological effects by activating five distinct GPCRs, known as Sst1 - Sst5. In order to fulfill their function, these receptors must be delivered from inside the cell to the cell surface, a process that is tightly regulated by the cell. The Stroh lab investigates how cells regulate their sensitivity to somatostatin by controlling the availability of different types of somatostatin receptors on the cell surface.

Dysfunctions of the somatostatin system are frequently caused by neuroendocrine tumours of the pituitary gland or the gastro-intestinal system and have been implicated in a number of disorders such as acromegaly, gigantism, Alzheimer's disease and schizophrenia. Work in the Stroh lab is aimed at providing a deeper understanding of the mechanisms regulating the sensitivity of the somatostatin system and, by analogy, other GPCR signalling systems. This work may contribute to the design of more effective drugs and new therapeutic approaches.