Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, C115

Oral Communications

Environmental enrichment facilitates long-term potentiation within striatal grafts transplanted into a mouse model of Huntington’s disease

D. M. Mazzocchi-Jones1, M. D. Dobrossy1, S. B. Dunnett1

1. School of Biosciences, Cardiff University, Cardiff, United Kingdom.

We have previously demonstrated that Embryonic striatal grafts express long-term potentiation (LTP) and long-term depression (LTD) consistent with the normal striatum (Mazzocchi-Jones, et al 2005). Previous analysis of environmental enrichment on graft function has demonstrated an increase in performance on a number of tasks involving motor learning (Dobrossy et al, 2005). In this present study we investigate the effect of enrichment on host-graft synaptic plasticity. Mice were raised in two environments, ‘standard’ animals were housed in pairs, and ‘enriched’ animals were housed in groups of 6, with numerous environmental stimuli. Following suitable habitation time mice were anaesthetised in an induction chamber, via Isoflourane, and maintained on this anaesthesia throughout the entire, and all, surgical procedures. Mice receiving striatal grafts were subjected to quinolinic acid induced unilateral lesions of the striatum. Seven days later all lesioned mice received a unilateral transplant of embryonic striatal tissue, obtained from E17 PrP-L-EGFP-L transgenic mice. Beginning at four weeks post-transplantation mice were euthanased via cervical dislocation, and brain slices were produced for in vitro recording. Environmental enrichment had no significant effect on the level of LTP and LTD observed in control mice (n=7) when compared to control mice housed in standard environments (n=8) (ANOVA, followed by Newman Kheuls Post-Hoc. Groups, F(1,13)=3.00, p=0.10, n.s.). Similarly, there was no significant difference in the level of LTD observed in grafted mice from enriched environments (n=8) when compared to grafted mice housed in control environments (n=5) (ANOVA, followed by Newman Kheuls Post-Hoc. Groups, F(1,11)=0.10, p=0.91, n.s.). However, there was a significant facilitation of LTP in grafted animals housed in enriched environments (n=12), when compared to those housed in standard environments (n=8) (ANOVA, followed by Newman Kheuls Post-Hoc. Groups, F(1,19)=8.41, p=<0.001). Previous analysis of the effect of environmental enrichment on graft function has shown an increase in Brain derived neurotrophic factor (BDNF) levels (Dobrossy et al, 2005). Tissue samples of various brain regions were isolated and subjected to an ELISA to assess BDNF levels. Environmental enrichment resulted in an increase in BDNF levels across samples, with a significantly greater increase in levels of BDNF observed in the grafted striatum, compared to both the normal and grafted striatum from standard environments (ANOVA, Standard Graft n=3, Standard Control n=3, Standard Enriched n=3, Graft Enriched n=3. Groups, F(1,23)=47.43, p=<0.001).

Where applicable, experiments conform with Society ethical requirements