Environmental enrichment reveals deficits in LTP in ArcKR mice.
There is considerable evidence demonstrating that exposure to enriched
or complex environments positively influences neuronal structure and
(Rosenzweig & Bennett, 1996;
Nithianantharajah & Hannan, 2006;
Correa et al. , 2012;
Privitera et al. , 2020;
Cooper & Frenguelli, 2021).
((Privitera et al. , 2020) showed
that LTP magnitude at SC-CA1 synapses was enhanced by enriched
conditions compared to standard house wildtype mice, with no
enrichment-induced increase in basal synaptic transmission. In these
mice the basal expression of Arc was significantly reduced after
prolonged enrichment (Privitera et
al. , 2020). We also found that there were no significant changes in
basal synaptic transmission in WT mice, comparing standard house to
environmentally-enriched (compare Fig 1A and 4D). In contrast there does
appear to be a reduction in synaptic strength for ArcKR mice upon
enrichment which may reflect the persistence of Arc and the resultant
AMPA receptor internalisation. When we examined LTP (measured after 1
hour) and STP (short term potentiation, 5 minutes after induction) we
observed no significant difference in their amplitudes between
environmentally-enriched ArcKR and WT mice. We did however observe a
clear difference in the pattern of EPSP potentiation, with a difference
in the decay of potentiation after LTP induction. In standard-housed
conditions, the slope of fEPSPs remained enhanced to around the same
degree as with short term potentiation (STP, LTP magnitude
~ 95 % of STP) for both WT and ArcKR mice. Whereas in
environmentally-enriched mice, LTP decayed to ~ 78 % of
the STP level after an hour in ArcKR mice. The ratio of LTP to STP was
significantly different between the genotypes (unlike the absolute
magnitude of LTP, which may not have reached significance due to the
larger variation in magnitude between slices). Thus, environment
enrichment reveals an effect of ArcKR expression on potentiation. Recent
studies (reviewed in (France et
al. , 2022) have investigated the processes underlying STP and LTP and
have shown that it is possible to differentially regulate STP and LTP
using NMDA subunit-specific positive allosteric modulators and
antagonists. Thus, different NMDA receptors appear to contribute to
these two processes. It is unclear why expression of ArcKR has no effect
on STP and LTP in standard housed conditions, but it does in environment
enriched conditions. It is possible that changes in NMDA receptor
expression in environment enriched mice could be involved
(Rampon et al. , 2000) but this
needs to be further tested.