Perineuronal nets restrict the induction of long-term depression in the mouse hippocampal CA1 region

抄録

Background

Perineuronal nets (PNNs) are unique extracellular matrix structures that enwrap the soma and dendrites of neurons. The developmental maturation of PNNs has been shown to highly correlate with closure of critical period of plasticity in which appropriate experience molds neural network organization. Long-term depression (LTD) is a persistent activity-dependent decrease in the efficacy of synaptic transmission and a prominent feature of theoretical schemes for learning and memory. Of interest, early studies on LTD at hippocampal CA1 synapses reported an apparent decline in degree of LTD with increasing age. However, the actual mechanism underlying age dependence of LTD remains unclear. The present study examines the impact of PNN integrity on age-dependent decline in the efficacy of LTD at Schaffer collateral-CA1 synapses of mouse hippocampus.

Methods

Extracellular field potentials were used to compare the induction of LTD in hippocampal slices from C57BL/6 mice. LTD was induced by low-frequency stimulation (LFS) delivered at 1 Hz for 15 min (900 pulses), paired-pulse LFS (900 paired pulses, 20 ms paired-pulse interval) or bath application of (RS)-3,5-dihydroxyphenylglycine (DHPG). To digest PNNs, the hippocampal slices were treated with chondroitinase ABC (ChABC). Immunofluorescence staining was used for labeling and identifying the expression of PNNs in specific cell types.

Results

We observed a dramatic decline in degree of LFS-induced LTD with increasing age from postnatal day (P) 14 to P28 at Schaffer-collateral-CA1 synapses. PNNs tightly enwrap a subset of parvalbumin interneurons in hippocampal CA1 region. ChABC treatment resulted in the disruption of PNNs and enhanced the induction of LFS-induced LTD in adult mice (P60). Early-life enrichment accelerated the postnatal development of PNNs and the decline in degree of LTD. Experienced unpredictable and inescapable restraint-tail shock stress enhanced the induction of LFS-induced LTD in hippocampal CA1 region and occluded the subsequent enhancement of LTD by ChABC treatment in P60 mice.

Conclusions

Our findings indicate that the emergence of the PNNs correlate with the influence of age on LTD induction. We provide insight into a previously unrecognized role for PNNs in restricting plasticity at excitatory synapses onto hippocampal CA1 neurons.