Lu, Leutgeb, et al. (2013)


Lu, Leutgeb, et al. (2013) Impaired hippocampal rate coding after lesions of the lateral entorhinal cortex. Nature Neuroscience, 16(8): 1085-1093

The idea that the hippocampus forms new memories by binding objects to space, the foundation of cognitive map theory, had seemed so vague and hard to imagine the first time I had read about it. Following up on Deshmukh’s chapter about lateral entorhinal cortical (LEC) processing, I read the following paper in which the mechanisms that may underlie the binding of dissociated object and spatial information in the brain are made much more clear. As mentioned by Deshmukh (2014), the segregated LEC and MEC inputs to the hippocampus converge on DG and CA3 cells. So how do these cells simultaneously process this information?

The answer: separate coding mechanisms. 

Previous studies (to be reviewed) suggested that object information appears to be encoded by rate codes in the hippocampus, while the place fields contained in the ensemble of active CA3 neurons conveys spatial information.

Lu, Leutgeb, et al. (2014) performed LEC lesions and measured ensemble activity in two environments differing in the shape of their borders. They found that LEC lesions impaired rate remapping in different environments, while control mice exhibited clear differences in firing rate. Both groups showed no change in cells’ preferred place fields, i.e. the preferred spatial location that increases activity in each cell. The size of the LEC lesion correlated with rate remapping impairment. Interestingly, only lesions of the intermediate, and not the dorsolateral or ventromedial LEC seemed to have significant impacts on rate remapping. Also, the population of active neurons overlapped more in lesioned animals and was most affected by intermediate lesions. Similar results were found when two environments differed in colors of the walls, rather than shape, which preserved spatial relationships between environments.

In a rather cool experiment, the authors how minor compared to more pronounced differences in the shape of two environments would impact rate coding. They found a gradient in remapping where minor shifts resulted in minor rate differences, whereas greater changes in environment shape resulted in greater differences in the rate codes of the two environments. Animals with LEC lesions, though demonstrating a similar gradient demonstrated shifts in the rate code that were of a smaller magnitude than those of controls. Again, LEC lesions preserved place preference of recorded neurons.

Lastly, the LEC itself demonstrated no rate remapping in response to different environments.

Thus, the authors provide evidence that the LEC is at most minimally required for spatial representations, while being necessary for CA3 rate remapping. With regards to my previous post asking where object and spatial information may be bound, the authors write: 

Although some object­related informa­tion is likely to already be integrated with spatial information at the stage of the interconnections between LEC and MEC, a stronger and more complete convergence may occur downstream in the hippo­campus, in CA3 and dentate gyrus where lateral and medial perforant path axons apparently synapse on dendrites of the same principal cells. This medial-lateral convergence, in conjunction with local network processes, may be necessary for determining whether and how much a hippocampal cell is active inside its place field on a particular occasion.

As this study relates to Deshmukh’s hypothesis about a dissociation of LEC and MEC by processing external and internal information respectively, indeed the changes in color and shape appear to be processed in the LEC in order for rate remapping to occur, however, there is no exclusion of the MEC in processing external sensory information in this study. 



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