University of Toronto

Departments of Psychology and Zoology and Program in Neuroscience

 The M5 muscarinic receptor is important for sustained dopamine release and rewards. We are adding extra M5 receptors to dopamine neurons in the ventral tegmental area, using a new method called in vivo electroporation, to see if rats become more sensitive to brain-stimulation reward, or other functions that involve dopamine neurons.

  Hamsters with the tau mutation wake up 2-4 hours earlier each day than wild type hamsters.  Casein kinase 1ε appears to be the enzyme responsible for the mutation via changes in the circadian clock in the suprachiasmatic nucleus (SCN).  We are adding wild type genes for casein kinase 1ε to the SCN, using in vivo electroporation, to study  how and where normal genes combine with mutant genes to affect circadian behaviors.

  We have made knockout mice lacking the M5 muscarinic receptor gene, to show how critical this gene is for sustained dopamine functions. We are creating mice that overexpress the M5 gene, either in all cells or in catecholamine neurons.  These mice should be more responsive to brain-stimulation (in terms of dopamine release or rewards). If so, they might be more sensitive to drugs that induce reward, stereotypy or other behaviors used to model schizophrenia.

Brain stimulation reward and M5 receptor in rats

Circadian, sleep disorder and genes

Startle reflex and emotion learning mechanisms

 

M5 transgenic mice

Some Current Projects

  We have defined many brain stem circuits responsible for startle, startle inhibition, and startle potentiation. We are interested in how these circuits are activated and inhibited by cholinergic, GABAergic and glutamatergic genes added to the critical neurons in the pontine reticular formation, dorsal tegmentum, and amygdala.