Description:

Neural activity in the dentate gyrus (DG) is required for the detection and discrimination of novelty, context and patterns, amongst other cognitive processes. Previous studies have shown that granule cell activation differs between the supra and infrapyramidal blades of the DG during a range of hippocampal dependent tasks yet how excitatory dynamics within the DG drive and modulate this blade-specific bias under varying cognitive demands remains unclear. Here we used an automated touch screen pattern separation task combined to temporally controlled tagging of active neurons to determine how increasing cognitive demand shapes the spatial patterns of activity in the DG. We observed that as task difficulty increased, DG activation became progressively biased toward the suprapyramidal blade, accompanied by structured distributions of active mature granule cells (mGCs) along the apex-to-blade and hilar-to-molecular layer axes. Selective inhibition of mature granule cells (mGCs) did not affect the patterned distribution of active cells but profoundly impaired performance, as mice were no longer able to discriminate between closely spaced locations. In contrast, chemogenetic inhibition of adult-born granule cells (abDGCs) beyond a critical window of their maturation significantly impaired performance of mice during high-demand conditions, elevated overall mGC activity and disrupted the blade-specific distribution of active mGCs even in animals that successfully completed the task. These findings demonstrate how a high cognitive demand pattern separation task preferentially activates mGCs in subregions of the DG and are consistent with a modulatory role for abDGCs on the dentate circuit which in part governs the spatially organized patterns of activity of mGCs. 

Charlotte Castillon PhD,  
Postdoctoral Researcher 
Contractor Lab 
Department of Neuroscience