Structural development and dorsoventral maturation of the medial entorhinal cortex

Abstract

We investigated the structural development of superficial-layers of medial entorhinal cortex and parasubiculum in rats. The grid-layout and cholinergic-innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout development. Layer-3 and parasubiculum neurons had a transient calbindin-expression, which declined with age. Early postnatally, layer-2 pyramidal but not stellate-cells co-localized with doublecortin – a marker of immature neurons – suggesting delayed functional-maturation of pyramidal-cells. Three observations indicated a dorsal-to-ventral maturation of entorhinal cortex and parasubiculum: (i) calbindin-expression in layer-3 neurons decreased progressively from dorsal-to-ventral, (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than ventral parasubiculum. The early appearance of calbindin-pyramidal-grid-organization in layer-2 suggests that this pattern is instructed by genetic information rather than experience. Superficial-layer-microcircuits mature earlier in dorsal entorhinal cortex, where small spatial-scales are represented. Maturation of ventral-entorhinal-microcircuits – representing larger spatial-scales – follows later around the onset of exploratory behavior.

DOI: http://dx.doi.org/10.7554/eLife.13343.001

eLife digest

Many animals, from rats to humans, need to navigate their environments to find food or shelter. This ability relies on a kind of memory known as spatial memory, which provides a map of the outside world within the animal’s brain. Specifically, cells in a part of the brain called the medial entorhinal cortex act like the grids present on a map, and are known as grid cells. Other cells in this region represent boundaries in the environment and are known as border cells. These cells and other cells connect to each other to make the spatial memory circuit.

Previous research had reported that the grid cells were not present in the very early stages of an animal’s life. It was also not clear how the different cell types involved in spatial memory develop after birth. Ray and Brecht have now studied rats and found that certain characteristic structures in the circuit are present at birth. For example, cells that were most likely to become grid cells, were already laid out in a grid, indicating that this layout is instructed by genetic information rather than experience.

Ray and Brecht also found that the cells that most likely become grid cells matured later than the cells that most likely become border cells. Further analysis then revealed that the circuits in the top part of the medial entorhinal cortex, which represents nearby areas, matured earlier than those in the bottom part of this region, which represent farther areas. These findings could therefore explain why rats explore nearby areas earlier in life before going on to explore further away areas at later stages.

More work is needed to characterize other components of the neural circuits involved in spatial memory to provide a complete understanding of how these memories are formed. Future experiments could also ask if encouraging young rats to explore a wider area can cause the circuits to mature more quickly.

DOI: http://dx.doi.org/10.7554/eLife.13343.002