SSA: Noradrenergic modulation of hippocampal function

The hippocampus is critical for the encoding and recall of episodic memories in the brain. It is believed that the process of pattern separation, whereby components of episodic memories are dissected, is performed at inputs to dentate granule cells whereas pattern completion, where the details of episodic memories are brought together, is performed at synapses between CA3 pyramidal cells. The link between these two regions is the mossy fibre pathway that transmits information from granule cells in the dentate gyrus to pyramidal cells and interneurons in the CA3 region. The hippocampus is also strongly implicated in the encoding of novelty via inputs from the noradrenergic system, which densely innervates the hippocampus and in particular the dentate gyrus and CA3 regions. Therefore, it is hypothesized that dentate gyrus and CA3 network function will be transformed by the release of noradrenaline.
During the rotation project the student will design and implement a network model for the effect of mossy fibre transmission on CA3 network activity building on similar models already implemented in our labs. The aim will be to combine biophysically plausible descriptions of the electrical activity of principal excitatory neurons and inhibitory interneurons in the hippocampus with the hypothesised actions of noradrenaline on distinct neuronal subtypes. This model will then be tested experimentally by investigating the CA3 network response to mossy fibre activity in hippocampal slices and the alterations caused by activation of noradrenergic receptors. The project will develop to include a dissection of the roles of noradrenergic receptors located on distinct neuronal subtypes. These may be individually modelled and separately stimulated experimentally using a combination of electrophysiology, pharmacology and optogenetic techniques.