The Neuro Team

Complex Neural Systems is a multidisciplinary unit whose investigators probe the brain’s structure, chemistry and physiology as related to functions of cerebral blood flow, sensory and motor activities, sleep-wake states and memory. Knowing the structures and processes by which these systems work will help to understand their dysfunction in neurological diseases such as migraine headaches, motor disorders, sleep disorders and Alzheimer’s disease.

Researchers

• de Villers Sidani, Etienne
• Guitton, Daniel
• Hamel, Edith
• Jones, Barbara E.
• Pack, Christopher
• Shmuel, Amir
• Stroh, Thomas

Publications

Receptors for the neuropeptide neurotensin (in red and blue) mapped against cells containing vasoactive intestinal peptide (outlined in white)

Opioid receptors: Opioid drugs such as morphine and endogenous opioids are agonists at a family of receptors referred to as delta-, kappa-, and mu-opioid receptors. Although most opioid analgesic drugs used to date act upon the mu receptor, recent studies suggest that drugs targeted at the delta receptor may produce analgesia with considerably less undesirable effects than the ones acting on mu. Research in Dr. Beaudet’s laboratory, therefore, focussed on mechanisms regulating the sensitivity and availability of delta opioid receptors in the brain and spinal cord, with the aim of improving the therapeutic efficacy of delta drugs. A novel in vivo internalization assay using a fluorescent derivative of the DOR-specific agonist deltorphin has proven extremely powerful for identifying neurons highly responsive to delta-acting drugs in the spinal cord and in dorsal root ganglia of the rat.

Neurotensin receptors: The neuropeptide Neurotensin (NT) has been implicated in a variety of biological functions such as antinociception and neuroendocrine regulation. It binds two G protein-coupled receptor subtypes in the brain, designated NTS1 and NTS2. Dr. Beaudet’s work has been seminal in characterizing mechanisms of NT signalling and particularly in establishing the importance of receptor internalization and trafficking in this process. More recently, Dr. Beaudet’s laboratory characterized the distribution of NTS2 receptor in the rat central nervous system, unravelled the signalling system which this receptor was coupled to in the brain, and demonstrated that it played a key role in mediating antinociception in the rat spinal cord.

Somatostatin receptors: Somatostatin (Somatotropin Release-Inhibiting Factor; SRIF) is one of the main factors controlling the release of growth hormone (GH), among several other central and peripheral functions. It exerts its biological effects through a family of five G protein-coupled receptors designated sst1 - sst5. Of these, sst1 and sst2 appear to be critically involved in the hypothalamic regulation of growth hormone release, whereas sst2 and sst5 have been shown to co-operate in mediating SRIF regulation of GH release from pituitary somatotrophs. In recent years, work in Dr. Beaudet’s laboratory demonstrated that stimulation by SRIF induces a rapid and efficient internalization of sst2 and sst5 receptors and that internalization of sst2 constitutes a pivotal step in signaling by this receptor subtype. His studies also showed that the presence of sst5 receptors exerts and influence on the regulation of sst2 receptor cell surface availability and that this receptor plays a critical role in preventing cell desensitization to SRIF.