Adult-born dentate granule cells promote hippocampal population sparsity

The dentate gyrus (DG) gates neocortical information flow to the hippocampus. Intriguingly, the DG also produces adult-born dentate granule cells (abDGCs) throughout the lifespan, but their contribution to downstream firing dynamics remains unclear. Here, we show that abDGCs promote sparser hippocampal population spiking during mnemonic processing of novel stimuli. By combining triple-(DG-CA3-CA1) ensemble recordings and optogenetic interventions in behaving mice, we show that abDGCs constitute a subset of high-firing-rate neurons with enhanced activity responses to novelty and strong modulation by theta oscillations. Selectively activating abDGCs in their 4–7-week post-birth period increases sparsity of hippocampal population patterns, whereas suppressing abDGCs reduces this sparsity, increases principal cell firing rates and impairs novel object recognition with reduced dimensionality of the network firing structure, without affecting single-neuron spatial representations. We propose that adult-born granule cells transiently support sparser hippocampal population activity structure for higher-dimensional responses relevant to effective mnemonic information processing.


Statistics
For all statistical analyses, confirm that the following items are present in the figure legend, table legend, main text, or Methods section.
n/a Confirmed The exact sample size (n) for each experimental group/condition, given as a discrete number and unit of measurement A statement on whether measurements were taken from distinct samples or whether the same sample was measured repeatedly The statistical test(s) used AND whether they are one-or two-sided Only common tests should be described solely by name; describe more complex techniques in the Methods section.
A description of all covariates tested A description of any assumptions or corrections, such as tests of normality and adjustment for multiple comparisons A full description of the statistical parameters including central tendency (e.g. means) or other basic estimates (e.g. regression coefficient) AND variation (e.g. standard deviation) or associated estimates of uncertainty (e.g. confidence intervals) For null hypothesis testing, the test statistic (e.g. F, t, r) with confidence intervals, effect sizes, degrees of freedom and P value noted

Software and code
Policy information about availability of computer code Data collection Neural data was acquired using the integrated circuit RHD2164 from Intan Technologies; and unit isolation was performed using Kilosort 1.0 via the Spikeforest (v1) sorting framework. Confocal images were acquired using the ZEN (Zeiss Black 2.3) software.
For manuscripts utilizing custom algorithms or software that are central to the research but not yet described in published literature, software must be made available to editors and reviewers. We strongly encourage code deposition in a community repository (e.g. GitHub). See the Nature Research guidelines for submitting code & software for further information.

Data
Policy information about availability of data All manuscripts must include a data availability statement. This statement should provide the following information, where applicable: -Accession codes, unique identifiers, or web links for publicly available datasets -A list of figures that have associated raw data -A description of any restrictions on data availability The datasets generated during and/or analysed during the current study will be made available via the MRC BNDU Data Sharing Platform (https:// data.mrc.ox.ac.uk/) on reasonable request.

nature research | reporting summary
April 2020 Field-specific reporting Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences
For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf

Life sciences study design
All studies must disclose on these points even when the disclosure is negative.

Sample size
The dataset includes n=5,158 principal cells and n=361 interneurons recorded from the hippocampus. A total of 26 mice were used in the electrophysiology experiments, and a further 16 in the lesion experiment. No statistical methods were used to pre-determine sample sizes but our sample sizes are similar to those reported in previous publications (e.g. ref 12, 13, 14, 16).
Data exclusions No mice were excluded. Inclusion criteria for well-isolated single units were used as published in previous studies and described in the methods section. For population dimensionality analysis, the recording day had to contain >10 simultaneously recorded principal cells for inclusion.
Randomization Mice were randomly allocated to ArchT and GFP-only groups. In the novel object recognition task, objects and their positions and the order of their replacement was randomized.

Blinding
Data collection could not be performed blind to the conditions of the experiments since the experimenters had to be aware as to which conditions they had to expose each mouse on a given day and on a given session (e.g. Light-delivery OFF versus ON). Neural and behavioural data analyses were conducted in an identical way regardless of the identity of the experimental condition from which the data were collected, with the investigators blind to group allocation during data analysis of experiments (e.g. Light-delivery OFF versus ON).

Reporting for specific materials, systems and methods
We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material, system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response.