Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is a key incretin hormone, released from intestine after a meal, producing a glucose-dependent insulin secretion. The GIP receptor (GIPR) is expressed on large neurons, and GIP is synthetised in a subset of neurons in the brain. However, the role of the GIP receptor in neuronal signaling is not clear. In this study, we used a mouse strain with GIPR gene deletion (GIPR KO) in order to elucidate the specific role of the GIPR in the brain. Compared to C57Bl/6 control mice, GIPR KO mice displayed higher locomotor activity in an open-field task. Impairment of recognition and spatial learning and memory of GIPR KO mice were found in the object recognition task and a spatial water maze task, respectively. In an object location task, no impairment was found. GIPR KO mice also showed impaired synaptic plasticity in paired-pulse facilitation and a block of long-term potentiation in area CA1 of the hippocampus. Moreover, a large decrease in number of neuronal progenitor cells was found in the dentate gyrus of transgenic mice, though the numbers of young neurons was not changed. When taken together, the results suggest that GIP receptors play an important role in cognition, neurotransmission and cell proliferation.