Spatial Learning Requires mGlu5 Signalling in the Dorsal Hippocampus
- 297 Downloads
We examined the role of hippocampal metabotropic glutamate receptor 5 (mGlu5) in spatial learning and memory. Although it has been shown that mGlu5 signalling is required for certain forms of learning and memory, its role in spatial learning is unclear since studies using pharmacological or knockout mice models provide inconsistent findings. Additionally, the location in the brain where mGlu5 signalling may modulate such learning is yet to be precisely delineated. We stereotaxically injected rAAV-Cre into the dorsal hippocampus of mGlu5loxP/loxP mice to knockdown mGlu5 in that region. We show for the first time that knockdown of mGlu5 in the dorsal hippocampus is sufficient to impair spatial learning in Morris Water Maze. Locomotor activity and memory retrieval were unaffected by the mGlu5 knockdown. Taken together, these findings support a key role for dorsal hippocampal mGlu5 signalling in spatial learning.
KeywordsHippocampus mGlu5 Spatial learning
We are grateful to Dr Anis Contractor (Northwestern University, Chicago USA) for supply of mGlu5loxP/loxP mice. This research was supported by a project grant (APP1022201) from the National Health and Medical Research Council (NHMRC) of Australia awarded to AJL and JHK; Australian Research Council fellowships awarded to JRD and JHK, and NHMRC fellowships awarded to RADB and AJL. We acknowledge the Victorian Government’s Operational Infrastructure Support Program. We would also like to thank Dr Chris Bye and the Florey Behaviour Core Facility.
- 13.Ayala JE, Chen Y, Banko JL, Sheffler DJ, Williams R, Telk AN, Watson NL, Xiang Z, Zhang Y, Jones PJ, Lindsley CW, Olive MF, Conn PJ (2009) mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology 34(9):2057–2071PubMedCentralPubMedCrossRefGoogle Scholar
- 17.Anderson JJ, Rao SP, Rowe B, Giracello DR, Holtz G, Chapman DF, Tehrani L, Bradbury MJ, Cosford ND, Varney MA (2002) [3H]Methoxymethyl-3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine binding to metabotropic glutamate receptor subtype 5 in rodent brain: in vitro and in vivo characterization. J Pharmacol Exp Ther 303(3):1044–1051PubMedCrossRefGoogle Scholar
- 25.Kiyota T, Yamamoto M, Schroder B, Jacobsen MT, Swan RJ, Lambert MP, Klein WL, Gendelman HE, Ransohoff RM, Ikezu T (2009) AAV1/2-mediated CNS gene delivery of dominant-negative ccl2 mutant suppresses gliosis, [beta]-amyloidosis, and learning impairment of APP/PS1 mice. Mol Ther 17(5):803–809PubMedCentralPubMedCrossRefGoogle Scholar
- 33.Gerstein H, O’Riordan K, Osting S, Schwarz M, Burger C (2012) Rescue of synaptic plasticity and spatial learning deficits in the hippocampus of Homer1 knockout mice by recombinant Adeno-associated viral gene delivery of Homer1c. Neurobiol Learn Mem 97(1):17–29PubMedCentralPubMedCrossRefGoogle Scholar
- 34.Bach ME, Barad M, Son H, Zhuo M, Lu YF, Shih R, Mansuy I, Hawkins RD, Kandel ER (1999) Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc Natl Acad Sci (USA) 96(9):5280–5285CrossRefGoogle Scholar
- 36.Francesconi W, Cammalleri M (1022) Sanna PP (2004) The metabotropic glutamate receptor 5 is necessary for late-phase long-term potentiation in the hippocampal CA1 region. Brain Res 1–2:12–18Google Scholar