Patients with Duchenne Muscular Dystrophy (DMD) have an increased incidence of mild to moderate cognitive impairment with deficits in verbal, short-term and working memory (1). In addition to similar cognitive deficits being observed in the dystrophin-deficient mdx mouse model of DMD, hippocampal long-term potentiation (LTP), the cellular correlate of memory formation, is also altered in mdx mice relative to controls (2). Although typically found at low levels in healthy brains, interleukin (IL)-6 can be elevated in diseased brains where cognitive function is also impaired (3). The aim of the present study was to assess hippocampal LTP in wild type (WT) and mdx mice to determine if exposure to IL-6 modifies LTP. In accordance with the European Directive 2010/63/EU, mdx and WT mice (8-12 weeks old) were anaesthetised with isoflurane, decapitated and their whole brains removed. Hemispheres were sectioned into 300µm slices in ice-cold aCSF. Slices were maintained in either aCSF (control) or recombinant IL-6 (1nM) in aCSF for 1 hour before experimentation. LTP was induced in both WT and mdx slices by high frequency stimulation of Schaffer collateral fibres innervating neurons of the CA1 hippocampal region. Comparisons were subsequently made between the slope function of field excitatory postsynaptic potentials (fEPSP) in WT versus mdx, and untreated versus treated slices. All fEPSP slope speeds (mV/ms) are provided as a normalised percentage of averaged 20 minute fEPSP slope pre-LTP baselines. Statistical analyses were performed using unpaired t tests with data expressed as mean normalised post-LTP slope speed ± standard deviation. We found that the magnitude of LTP was significantly reduced in mdx slices relative to WT (187.3 ± 34% vs 209.9 ± 48%, n=5, p=0.005). Further, chronic exposure to IL-6 (1nM) significantly reduced LTP slope in WT slices relative to untreated controls (181.2 ± 18% vs 218.7 ± 49%, n= 4, p<0.0001). Chronic treatment of mdx slices with IL-6 (1nM) did not significantly affect the mean post-LTP EPSP slope relative to untreated controls. Interestingly, WT slices treated with recombinant IL-6 mirrored the reduced LTP pattern observed in mdx control experiments (WT= 181.2 ± 18%, n=4 vs mdx= 187.3 ± 34%, n=5). In contrast to previous findings, we have shown that LTP in mdx hippocampal slices was decreased relative to WT comparators. This may be a functional manifestation of the memory deficits described in mdx mice and DMD patients. Exposure to the pro-inflammatory cytokine IL-6 reduced post-LTP EPSP slope in WT hippocampal neurons to the reduced mean post-LTP EPSP slope observed in dystrophin-deficient mdx slices. IL-6 did not impact upon LTP generation in mdx mice. Thus, in mdx mice, chronic exposure to elevated IL-6 may contribute to impaired memory formation.