Development of Parvalbumin-Expressing Basket Terminals in Layer II of the Rat Medial Entorhinal Cortex

Abstract

Grid cells in layer II of the medial entorhinal cortex (MEC LII) generate multiple regular firing fields in response to the position and speed of an individual within the environment. They exhibit a protracted postnatal development and, in the adult, show activity differences along the dorsoventral axis (DVA). Evidence suggests parvalbumin-positive (PV+) interneurons, most of which are perisomatic-targeting cells, play a crucial role in generation of the hexagonal grid cell activity pattern. We therefore hypothesized that the development and organization of PV+ perisomatic terminals in MEC LII reflects the postnatal emergence of the hexagonal firing pattern and dorsoventral differences seen in grid cell activity. We used immuno-electron microscopy to examine the development of PV+ perisomatic terminals and their target somata within dorsal and ventral MEC LII in rats of postnatal days (P)10, 15 and 30. We demonstrate that in dorsal and ventral MEC LII, the cross-sectional area of somata and number and density of perisomatic PV+ terminals increase between P10 and P15. A simultaneous decrease was observed in cross-sectional area of PV+ terminals. Between P15 and P30, both MEC regions showed an increase in PV+ terminal size and percentage of PV+ terminals containing mitochondria, which may enable grid cell activity to emerge and stabilize. We also report that dorsal somata are larger and apposed by more PV+ terminals than ventral somata at all stages, suggesting a protracted maturation in the ventral portion and a possible gradient in soma size and PV+ basket innervation along the DVA in the adult.

Significance Statement Grid cells within layer II of the medial entorhinal cortex produce a regular firing pattern in response to the environment during exploration. This pattern emerges after eye-opening in rodents and exhibits a gradient along the dorsoventral axis. Input from parvalbumin-expressing (PV+) interneurons is crucial for maintaining the grid pattern; however, how the PV+ innervation develops is unclear. Here we examine the structural development of dorsal and ventral perisomatic PV+ terminals and target somata. We show that the size of grid-related somata and number of PV+ terminals increase before eye-opening whereas PV+ terminals increase in size during grid activity stabilization. We further demonstrate that maturation in the ventral part is delayed, and that there are dorsoventral differences in young adults.