Deletion of the amyloid precursor-like protein 1 (APLP1) enhances excitatory synaptic transmission, reduces network inhibition but does not impair synaptic plasticity in the mouse dentate gyrus.
Amyloid precursor-like protein 1 (APLP1) is a transmembrane synaptic protein belonging to the amyloid precursor protein (APP) gene family. Although the role of this gene family-in particular of APP-has been intensely studied in the context of Alzheimer's disease, the physiological roles of its family members remain poorly understood. In particular, the function of APLP1, which is predominantly expressed in the nervous system, has remained enigmatic. Since APP has been implicated in synaptic plasticity, we wondered whether APLP1 could play a similar role. First, using in situ hybridization and laser microdissection combined with reverse transcription-quantitative polymerase chain reaction (PCR) we observed that Aplp1 mRNA is highly expressed in dentate granule cells. Having this examined, we studied synaptic plasticity at the perforant path-granule cell synapses in the dentate gyrus of APLP1-deficient mice in vivo. Analysis of field excitatory postsynaptic potentials evoked by stimulation of perforant path fibers revealed increased excitatory transmission in APLP1-deficient mice. Moreover, we observed decreased paired-pulse inhibition of population spikes indicating a decrease in network inhibition upon deletion of APLP1. In contrast, short-term presynaptic plasticity (STP) as well as long-term synaptic plasticity (LTP) was unchanged in the absence of APLP1. Based on these results we conclude that APLP1 deficiency on its own does not lead to defects in synaptic plasticity, but affects synaptic transmission and network inhibition in the dentate gyrus.
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, Frankfurt am Main, Germany.
Matej
M
Vnencak
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, Frankfurt am Main, Germany.
Mandy H
MH
Paul
Department of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Meike
M
Hick
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, Frankfurt am Main, Germany.
Stephan W
SW
Schwarzacher
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, Frankfurt am Main, Germany.
Domenico
D
Del Turco
Department of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Ulrike C
UC
Müller
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, Frankfurt am Main, Germany.
Thomas
T
Deller
Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, Frankfurt am Main, Germany.
Peter
P
Jedlicka
D000200:Action Potentials / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018891:Dentate Gyrus / Q000502:physiology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D042282:Microdissection; D008839:Microelectrodes; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D019580:Perforant Pathway / Q000502:physiology; D065808:Prepulse Inhibition / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; D012333:RNA, Messenger
AB_514497; Alzheimer's disease; MGI_MGI:2154545; amyloid precursor protein (APP); granule cell; long-term potentiation; paired-pulse inhibition; perforant path