Title: Lateralisation of hippocampal memory function in mice The hippocampus is a cortical structure of importance for certain forms of memory. In humans, hippocampal function is lateralised, often assumed to be linked to the location of the language centre in the left hemisphere. However, it was recently discovered that there is a difference in synaptic plasticity between the left and right hippocampus in mice, raising the possibility of more fundamental functional differences between the two sides. The aim of the proposed project is to use optogenetics to unravel these differences. Optogenetics is a technique that enables cell type- and location-specific activation and silencing of neurons. Using this technique, we recently demonstrated that the magnitude of long-term potentiation of synaptic transmission (LTP) depends on whether the presynaptic input originates in the left or right hippocampus. In fact, whereas left input shows robust LTP, there is no LTP in the right input (Kohl et al., 2011). Moreover, when we silence left or right input during a spatial memory task in awake behaving mice, long-term memory is impaired following left silencing, but intact following right silencing (Shipton et al., unpublished). The aim of the PhD project is to use optogenetics to investigate further this left-right asymmetry in hippocampal function. Depending on the interests of the student, the research question addressed could be at any level from the molecular mechanisms of this synaptic left-right asymmetry to its neural circuit consequences and relation to behaviour.
- Kohl MM, Shipton OA, Deacon RM, Rawlins JNP, Deisseroth K and Paulsen O (2011) Hemisphere-specific optogenetic stimulation reveals left-right asymmetry of hippocampal plasticity. Nat Neurosci 14: 1413-1415.
- Shipton OA, Leitz JR, Dworzak J, Acton CEJ, Tunbridge EM, Denk F, Dawson HN, Vitek MP, Wade-Martins R, Paulsen O and Vargas-Caballero M (2011) Tau protein is required for amyloid β–induced impairment of hippocampal long-term potentiation. J Neurosci 31: 1688-1692.
- Shipton OA and Paulsen O (2013) GluN2A and GluN2B subunit-containing NMDA receptors in hippocampal plasticity. Philos Trans B 369: 20130163.