Early postnatal experience shapes both inhibitory and excitatory networks in the hippocampus. However, the underlying circuit plasticity is unclear. Using an enriched environment (EE) paradigm, we assessed the circuit plasticity of inhibitory cell-types in the hippocampus. We found that cholecystokinin (CCK)-expressing basket cells strongly increased somatic inhibition on the excitatory granular cells (GC) following EE while another pivotal inhibitory cell-type, parvalbumin (PV)-expressing cells did not show changes. By inhibiting activity of the entorhinal cortex (EC) using a chemogenetic approach, we demonstrate that the projections from the EC is responsible for the developmental plasticity of CCK+ basket cells. Our measurement of the input decorrelation by DG circuit suggests that EE has little effect on pattern separation despite of the altered CCK+ basket cell circuit. Altogether, our study places the activity-dependent remodeling of CCK+ basket cell innervation as a central process to adjust inhibition in the DG, while maintaining the computation in the circuit. Figure 5. PE housing has limited effect on pattern separation in the DG. (A) Top, cartoon depicting whole-cell recording of the GCs during simultaneous stimulation of the PP. Bottom, representative traces obtained in currentclamp mode in response to the stimulation with 5 input spike trains.To assess the level of pattern separation operated by single recorded GCs, the similarity of the inputs is compared to the similarity of the outputs using different comparative metrics. (B) Representative graphs of pattern separation with pairwise output similarity versus the pairwise input similarity measured by the three different metrics, including R, NDP and SF and using 10 ms bins. Data points below and above the dashed line correspond to pattern separation and pattern convergence, respectively. Solid lines represent the linear fits for the ANCOVA. Statistical comparisons were performed with an ANCOVA (the aoctool function in Matlab) and a two-sample t-test (*: p<0.05 and ***: p<0.001). (C) A summary for FR and p(Burst) (number of animals = 4 for both group, total 15 recordings for each group). Statistical comparisons were performed with a two-samples t-test for firing rate (t = 1.559, p = 0.13) and p(Burst) (t = 1.3627, p = 0.184). (D) Compactness, Occupancy or FR codes were measured for each recording sets. Statistical comparisons were performed with 2 sample t-test for binwise Compactness of output (t = 1.04, p = 0.307), the variations of Occupancy (t = 1.924, p = 0.073) and the variations in FR or spike trains (t = 1.129, p = 0.269). For each bars, the number of animals and the number of recorded cells used for the quantification are reported (a/n).
Early postnatal experience shapes both inhibitory and excitatory networks in the hippocampus. However, the underlying circuit plasticity is unclear. Using an enriched environment (EE) paradigm during the preweaning period in mice of either sex, we assessed the circuit plasticity of inhibitory cell types in the hippocampus. We found that cholecystokinin (CCK)-expressing basket cells strongly increased somatic inhibition on the excitatory granular cells (GCs) following EE, whereas another pivotal inhibitory cell type, parvalbumin (PV)-expressing cells, did not show changes. Using electrophysiological analysis and the use of cannabinoid receptor 1 (CB1R) agonist WIN 55 212-2, we demonstrate that the change in somatic inhibition from CCK1 neurons increases CB1R-mediated inhibition in the circuit. By inhibiting activity of the entorhinal cortex (EC) using a chemogenetic approach, we further demonstrate that the activity of the projections from the EC mediates the developmental assembly of CCK1 basket cell network. Altogether, our study places the experience-dependent remodeling of CCK1 basket cell innervation as a central process to adjust inhibition in the dentate gyrus and shows that cortical inputs to the hippocampus play an instructional role in controlling the refinement of the synaptic connections during the preweaning period.
The development, maturation, and plasticity of neural circuits are strongly influenced by experience and the interaction of an individual with their environment can have a long-lasting effect on cognitive function. Using an enriched environment (EE) paradigm, we have recently demonstrated that enhancing social, physical, and sensory activity during the pre-weaning time in mice led to an increase of inhibitory and excitatory synapses in the dentate gyrus (DG) of the hippocampus. The structural plasticity induced by experience may affect information processing in the circuit. The DG performs pattern separation, a computation that enables the encoding of very similar and overlapping inputs into dissimilar outputs. In the presented study, we have tested the hypothesis that an EE in juvenile mice will affect DG’s functions that are relevant for pattern separation: the decorrelation of the inputs from the entorhinal cortex (EC) and the recruitment of the principal excitatory granule cell (GC) during behavior. First, using a novel slice electrophysiology protocol, we found that the transformation of the incoming signal from the EC afferents by individual GC is moderately affected by EE. We further show that EE does not affect behaviorally induced recruitment of principal excitatory GC. Lastly, using the novel object recognition task, a hippocampus-dependent memory test, we show that the ontogeny of this discrimination task was similar among the EE mice and the controls. Taken together, our work demonstrates that pre-weaning enrichment moderately affects DG function.
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