These findings suggest that PR plays an unexplored and important role in the development of hippocampal circuitry and adult memory function. Chrysin 7-O-beta-gentiobioside mice) resulted in profound changes in neuronal migration with an absence of a distinct laminated granule cell layer, and granule cells scattered ectopically throughout the dentate gyrus (Frotscher et al., 2007; Zhao et al., 2004). first two weeks of life impaired adult performance on both the Chrysin 7-O-beta-gentiobioside novel object recognition and object placement memory tasks, two behavioral tasks hypothesized to describe facets of episodic-like memory in rodents. These findings suggest that PR plays an unexplored and important role in the development of hippocampal circuitry and adult memory function. mice) resulted in profound changes in neuronal migration with an absence of a distinct laminated granule cell layer, and granule cells scattered ectopically throughout the dentate gyrus (Frotscher et al., 2007; Zhao et al., 2004). This appears to be the result of failure of the radial glial scaffold to align radially (Frotscher, Haas, & Forster, 2003; Weiss et al., 2003). While we did not observe gross differences in granule cell layer morphology (e.g., ectopic cell localization) of rats treated postnatally with RU486 (unpubl. obs.), this does not preclude more subtle, but critical, alterations in granule cell layer architecture. For example, in heterozygous mice, in which reelin is reduced but not absent, there is little disruption in the gross morphology of the granule cell layer. However, dissociated hippocampal neurons of heterozygous mice show reduced numbers of dendritic spines, shorter spines, and reductions in molecular markers of synaptic machinery such as PSD-95 and NR2A subunits, reflecting lower levels of synaptic maintenance (S. Niu et al., 2008; Sanyong Niu, Renfro, Quattrocchi, Sheldon, & DArcangelo, 2004). Conversely, overexpression of reelin produces larger more complex spines, longer synaptic contacts and enriched spine apparatus in the outer MOL (Bosch, Muhaisen, Pujadas, Soriano, & Martnez, 2016; Pujadas et al., 2010). Taken together, these findings support the idea that PR regulation of reelin expression could be one mechanism by which the granule cell Rabbit Polyclonal to RPL10L layer undergoes proper development, thereby ensuring common recognition memory later in life. Cajal-Retzius neurons also function as pioneer neurons during the development of the perforant path, the main cortical input to the hippocampus, a process that is largely impartial of reelin (i.e., the perforant path forms normally in mice) (Victor Borrell et al., 2007; J. a Del Ro et al., 1997; Wu, Li, Yu, & Deng, 2008; Zhao, F?rster, Chai, & Frotscher, 2003). Terminals from the entorhinal cortex make temporary functional synapses with Cajal-Retzius neurons in the MOL, before ultimately forming mature synapses with dendrites of granule cells (Supr et al., 1998). Cajal-Retzius neurons likely guide pathway formation as they extend across the hippocampal fissure into the subiculum and entorhinal cortex (Ceranik et al., 1999; Ceranik, Zhao, & Frotscher, 2000) and may serve as a pathway for entorhinal axons entering into the MOL. Indeed, excitotoxic lesions of Cajal-Retzius neurons in hippocampal/entorhinal cocultures prevented entorhinal afferents from establishing their layer-specific synaptic targets within the MOL (Del Ro et al., 1997). Cajal-Retzius neurons can also induce axon regeneration from adult entorhinal cortex in hippocampal cocultures, eliciting axon growth from developmentally quiescent cortex, illustrating Cajal-Retzius neurons powerful chemoattractive effect (Del Ro, Sol, Borrell, Martnez, & Soriano, 2002). Changes in PR transcriptional activity during development could impact the target phenotype of Cajal-Retzius neurons, Chrysin 7-O-beta-gentiobioside thereby altering axon pathfinding of perforant path afferents and/or influencing mechanisms of synaptogenesis between entorhinal axons and granule cell dendrites in the MOL. This would profoundly alter Cajal-Retzius pioneer neuron function and alter hippocampal circuitry and subsequent behavior. Conclusions The present study demonstrates that PR, a powerful transcription factor, is usually expressed in Cajal-Retzius neurons of the molecular layer during a critical period of development for the perforant path and for dentate gyrus structure and circuitry. Inhibition of PR activity during this period impaired both recognition and contextual facets of episodic memory in adulthood, both of which are associated with hippocampal and entorhinal cortex afferent function. The present findings are consistent with the idea that PR activity during development.