Gunnersen Lab ~ Neuron Development and Plasticity Laboratory
Principal investigator: Dr Jenny Gunnersen
How do neurons make connections in the developing brain?
The aim of our research is to understand how neurons become connected to each other to form functional circuits. We investigate the formation of dendrites (branches) and inter-neuronal connections (synapses) in developing neurons in order to understand these processes in normal development and disease. Many neurological disorders are characterized by abnormal synaptic connectivity and changes in the number and strength of synaptic connections occur during learning and memory formation (termed plasticity). If we can understand how dendrites and synapses develop and change in the healthy brain, this knowledge will help us decipher the aberrant molecular pathways responsible for many cognitive disorders including mental retardation, epilepsy and schizophrenia.
Honours and PhD projects are available to investigate these questions, focussing on the roles of key molecules (e.g. Seizure-related gene 6 or Sez-6, Wnts, cytokines, Ndfip1) and the pathways in which they signal to regulate these important processes.
Sez-6 is a protein that is expressed in the developing brain and in adult neurons in regions important for learning and memory. To investigate the role of Sez-6, we produced a knockout mouse in which the Sez-6 gene was inactivated. Analyses of neurons in the cortex revealed that the dendrites of these neurons were abnormal, that the neurons were less easily excited by electrical stimulation and that there were fewer synapses providing excitatory input to these neurons. Abnormal Sez-6 function may be linked to the development of epileptic seizures and a Sez-6 family member is a candidate gene for autism. Furthermore, the dendrite and synapse abnormalities seen when Sez-6 is lacking are also seen in a number of mental retardation and neurodegenerative conditions.
To study the complex molecular pathways regulating the development of neuronal branches and synapses, we use diverse approaches, including real-time imaging using fluorescent markers of synapses, tissue-specific gene knockout or gene knockdown and a range of molecular biological and protein biochemical techniques.