TY - JOUR T1 - Postnatal development of functional projections from para- and presubiculum to medial entorhinal cortex in the rat JF - The Journal of Neuroscience JO - J. Neurosci. DO - 10.1523/JNEUROSCI.1623-19.2019 SP - 1623-19 AU - Cathrin B. Canto AU - Noriko Koganezawa AU - Mariá José Donate Lagartos AU - Kally C. O'Reilly AU - Huibert D. Mansvelder AU - Menno P. Witter Y1 - 2019/09/11 UR - http://www.jneurosci.org/content/early/2019/09/11/JNEUROSCI.1623-19.2019.abstract N2 - Neurons in parasubiculum (PaS), presubiculum (PrS) and medial entorhinal cortex (MEC) code for place (grid cells) and head direction. Directional input has been shown to be important for stable grid cell properties in MEC, and PaS and PrS have been postulated to provide this information to MEC. In line with this, head direction cells in those brain areas are present at postnatal day (P)11 having directional tuning that stabilizes shortly after eye-opening, which is before premature grid cells emerge in MEC at P16. Whether functional connectivity between these structures exists at those early postnatal stages is unclear. With the use of anatomical tracing, voltage-sensitive dye imaging and single cell patch recordings in female and male rat brain slices between P2-61, we determined when the pathways from PaS and PrS to MEC emerge, become functional, and how they develop. Anatomical connections from PaS and PrS to superficial MEC emerge between P4-6. Monosynaptic connectivity from PaS and PrS to superficial MEC was measurable from P9-10 onwards, whereas connectivity with deep MEC was measurable from P11-12. From P14/15 on, reactivity of MEC neurons to para- and presubicular inputs becomes adult-like and continues to develop until P28-30. The maturation of the efficacy of both inputs between P9-21 is paralleled by maturation of morphological properties, changes in intrinsic properties of MEC principal neurons and changes in the GABAergic network of MEC. In conclusion, synaptic projections from PaS and PrS to MEC become functional and adult-like before the emergence of grid cells in MEC.Significance statement:Head direction information, crucial for grid cells in medial entorhinal cortex (MEC), is thought to enter MEC via para- (PaS) and presubiculum (PrS). Unraveling the development of functional connections between PaS, PrS and MEC is key to understanding how spatial navigation, an important cognitive function, may evolve. To gain insight into the development, we utilized anatomical tracing techniques, voltage-sensitive dye imaging, and single cell recordings. The combined data led us to conclude that synaptic projections from PaS and PrS to MEC become functional and adult-like before eye-opening, allowing crucial head direction information to influence place encoding before the emergence of grid cells in rat MEC. ER -