Adult neurogenesis improves spatial information encoding in the mouse hippocampus

Abstract

Adult neurogenesis is a unique form of neuronal plasticity in which newly generated neurons are integrated into the adult dentate gyrus in a process that is modulated environmental stimuli. Adult-born neurons can contribute to spatial memory but it is unknown whether they alter neural representations of space in the hippocampus. Using in vivo two-photon calcium imaging, we found that mice that were previously housed in an enriched environment, which triggers an increase in neurogenesis, had increased spatial information encoding in the hippocampal dentate gyrus during novel context exposure. Ablating adult neurogenesis by prior focal irradiation of the hippocampus blocked the effect of enrichment and lowered spatial information content, as did the chemogenetic silencing of adult-born neurons. Both ablating neurogenesis and silencing adult-born neurons decreased the calcium activity rates of dentate gyrus neurons, resulting in a decreased amplitude of place-specific responses. These findings are in contrast to previous studies that suggested a predominantly inhibitory action for adult-born neurons. We propose that adult neurogenesis improves neural representations of space by increasing the gain of dentate gyrus neurons and thereby improving their ability to tune to spatial features. This mechanism may mediate the beneficial effects of environmental enrichment on spatial learning and memory.

Increased flexibility of CA3 memory representations following environmental enrichment

“…The increased spatial tuning of CA3 place cells in the enriched rats suggests that EE leads to more selective and more precise spatial information encoding in CA3, which could support better spatial memory. Combined with recent reports of enrichment-dependent increases of spatial tuning and spatial information in DG mature granule cells in novel environments 38 , these findings show that EE has clear effects on spatial tuning of place cells in the DG/CA3 network. Interestingly, our results stand in contrast to findings from CA1 28 which suggests that EE’s effects on spatial tuning of place cells might be limited to DG/CA3.…”

Delayed formation of neural representations of space in aged mice

“…Previous studies found that hippocampal activity in area CA3 becomes elevated during aging ( 18, 27 ). We determined single-cell calcium activity by measuring the area under the curve of transients and normalizing to the distance run by each mouse ( 28 ) (Fig. 1E-G).…”

“…Single-cell calcium activity was determined as previously described ( 58 ). Briefly, ΔF/F data was filtered with a zero phase shift, third order Butterworth lowpass filter.…”

“…Single-cell Fisher Information (FI) was calculated as previously described ( 58, 60 ). A bias-corrected signal to noise ratio was computed using the unfiltered ΔF/F fluorescence data for each individual cell, where the signal is the square of the difference of the mean activity at two locations on the treadmill, and the noise is the average variance of the activity at each location.…”

“…Statistics -Nested bootstrap analysis -When pooling cell data from different mice into a single experimental group, significance testing was done using a muti-level bootstrapped approach as previously described (29). To assess whether differences between two experimental groups are significant, a null surrogate distribution was constructed for each mouse in each group by resampling with substitution from the pool of all imaged cells.…”