Impaired long-term depression mediated by group I metabotropic glutamate receptors, but not muscarinic acetylcholine receptors in juvenile-onset diabetes rats

Abstract

Type 1 diabetes mellitus is a chronic disease where the destruction of insulin-producing pancreatic β cells causes hyperglycemia and its onset typically occurs during childhood or adolescence. We previously reported that long-term depression (LTD) in the CA1 region of the hippocampus, induced by a low-frequency stimulation to the Schaffer collaterals, was attenuated in juvenile-onset diabetes (JDM) rats. We herein investigated whether LTD was triggered by the activation of G-protein coupled group I metabotropic glutamate receptors (mGluR-LTD) or M1 muscarinic acetylcholine receptors (mAChR-LTD) at Schaffer collateral-CA1 synapses in hippocampal slices from JDM rats. Our results indicated that the magnitude of mGluR-LTD induced by the group I mGluRs agonist (S)-3,5-dihydroxyphenylglycine (DHPG) was smaller in JDM rats than in age-matched control rats. Paired-pulse facilitation (PPF) is primarily associated with enhanced presynaptic transmitter release. To investigate the interaction between PPF and mGluR-LTD, PPF ratios conducted at interstimulus intervals (ISIs) of 50 and 200 ms were compared at the baseline and LTD stage. In control rats, the PPF ratio at ISIs of 50 ms was higher during the mGluR-LTD stage than at the baseline. However, PPF ratios at ISIs of 50 and 200 ms were higher during the mGluR-LTD stage than at the baseline in JDM rats. In contrast, the magnitude of mAChR-LTD did not significantly differ between control and JDM rats. Therefore, the expression of mGluR-LTD in JDM rats may be associated with presynaptic changes, since the increase in the PPF ratio occurred concomitantly with the attenuation of LTD.