Rearing-environment-dependent hippocampal local field potential differences in wild-type and inositol trisphosphate receptor type 2 knockout mice.

KEY POINTS: Mice reared in an enriched environment are demonstrated to have larger hippocampal gamma oscillations than those reared in isolation, thereby confirming previous observations in rats. To test whether astrocytic Ca2+ surges are involved in this experience-dependent LFP pattern modulation, we used inositol trisphosphate receptor type 2 (IP3 R2)-knockout (KO) mice, in which IP3 /Ca2+ signalling in astrocytes is largely diminished. We found that this experience-dependent gamma power alteration persists in the KO mice. Interestingly, hippocampal ripple events, the synchronized events critical for memory consolidation, are reduced in magnitude and frequency by both isolated rearing and IP3 R2 deficiency. ABSTRACT: Rearing in an enriched environment (ENR) is known to enhance cognitive and memory abilities in rodents, whereas social isolation (ISO) induces depression-like behaviour. The hippocampus has been documented to undergo morphological and functional changes depending on these rearing environments. For example, rearing condition during juvenility alters CA1 stratum radiatum gamma oscillation power in rats. In the present study, hippocampal CA1 local field potentials (LFP) were recorded from bilateral CA1 in urethane-anaesthetized mice that were reared in either an ENR or ISO condition. Similar to previous findings in rats, gamma oscillation power during theta states was higher in the ENR group. Ripple events that occur during non-theta periods in the CA1 stratum pyramidale also had longer intervals in ISO mice. Because astrocytic Ca2+ elevations play a key role in synaptic plasticity, we next tested whether these changes in LFP are also expressed in inositol trisphosphate receptor type 2 (IP3 R2)-knockout (KO) mice, in which astrocytic Ca2+ elevations are largely diminished. We found that the gamma power was also higher in IP3 R2-KO-ENR mice compared to IP3 R2-KO-ISO mice, suggesting that the rearing-environment-dependent gamma power alteration does not necessarily require the astrocytic IP3 /Ca2+ pathway. By contrast, ripple events showed genotype-dependent changes, as well as rearing condition-dependent changes: ISO housing and IP3 R2 deficiency both lead to longer inter-ripple intervals. Moreover, we found that ripple magnitude in the right CA1 tended to be smaller in IP3 R2-KO. Because IP3 R2-KO mice have been reported to have depression phenotypes, our results suggest that ripple events and the mood of animals may be broadly correlated.