Region- and layer-specific cell characteristics are common throughout the mammalian cerebral cortex. In the medial entorhinal cortex (mEC) layer V pyramidal neurons show the persistent, graded activity profile deemed to underpin working memory (WM) function (Egorov et al., 2002), whilst layer II stellate neurons exhibit spatial grid cell firing characteristics (Hafting et al., 2005). Organisational and connectivity differences have been established between these layers, but there is currently no mechanistic molecular explanation as to how they support their diverse computational functions. The aim of this PhD will be to generate and test hypotheses regarding how layer- and cellspecific molecular machinery confers the electrophysiological profile of layer V cells. This will entail the relatively novel approach of examining the identity, colocalisation, expression level gradients and combinatorial expression of the hundreds of genes enriched in the mEC and specifically layer V. This will enable hypotheses to be generated and tested and the results could predict and explain further functional differentiation, provide insight into why layers are selectively vulnerable to pathology and provide a framework for highly specific genetic targeting of mEC neurons.
Related Publications and Presentations
- Helen L Ramsden, T. Ian. Simpson, and Matthew Nolan, “Gene Expression Patterns Reflect Anatomical And Physiological Variation In Adult Mouse Medial Entorhinal Cortex”, FENS Abstracts, 2012.
- Helen L Ramsden, and Matthew Nolan, “Exploration induces hippocampus-independent up-regulation of Arc in layer V of mouse medial entorhinal cortex”, Champalimaud Neuroscience Symposium, 2012.