title: Dysfunction of Somatostatin-Positive Interneurons Associated with Memory Deficits in an Alzheimer's Disease Model.
abstract: Alzheimer's disease (AD) is characterized by cognitive decline and neuronal network dysfunction, but the underlying mechanisms remain unknown. In the hippocampus, microcircuit activity during learning and memory processes is tightly controlled by O-LM interneurons. Here, we investigated the effect of beta-amyloidosis on O-LM interneuron structural and functional connectivity, combining two-photon in vivo imaging of synaptic morphology, awake Ca2+imaging, and retrograde mono-transsynaptic rabies tracing. We find severely impaired synaptic rewiring that occurs on the O-LM interneuron input and output level in a mouse model of AD. Synaptic rewiring that occurs upon fear learning on O-LM interneuron input level is affected in mice with AD-like pathology. This process requires the release of acetylcholine from septo-hippocampal projections. We identify decreased cholinergic action on O-LM interneurons in APP/PS1 mice as a key pathomechanism that contributes to memory impairment in a mouse model, with potential relevance for human AD.
authors.affiliation: Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Lena C
authors.initials: LC
authors.lastname: Schmid
authors.affiliation: Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mittag
authors.affiliation: Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Poll
authors.affiliation: Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Steffen
authors.affiliation: Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Neuronal Networks Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Hans-Rüdiger
authors.initials: HR
authors.lastname: Geis
authors.affiliation: Functional Neuroconnectomics Group, Department of Epileptology, Medical School, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Inna
authors.initials: I
authors.lastname: Schwarz
authors.affiliation: Clemens-Schöpf-Institute, Technical University of Darmstadt, 64289 Darmstadt, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: Functional Neuroconnectomics Group, Department of Epileptology, Medical School, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schwarz
authors.affiliation: Neuronal Networks Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Remy
authors.affiliation: Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. Electronic address: martin.fuhrmann@dzne.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Fuhrmann
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000009:adverse effects; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D005239:Fear; D005968:Glutamate Decarboxylase / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007395:Interneurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008569:Memory Disorders / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D056347:Neuroanatomical Tract-Tracing Techniques; D009473:Neuronal Plasticity / Q000502:physiology*; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000473:pathology / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D013004:Somatostatin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D003024:Clozapine; C079149:clozapine N-oxide; D000109:Acetylcholine