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@ARTICLE{Lenz:277141,
      author       = {M. Lenz and A. Eichler and P. Kruse and C. Galanis and D.
                      Kleidonas and G. Andrieux and M. Börries$^*$ and P.
                      Jedlicka and U. C. Müller and T. Deller and A. Vlachos},
      title        = {{T}he amyloid precursor protein regulates synaptic
                      transmission at medial perforant path synapses.},
      journal      = {The journal of neuroscience},
      volume       = {43},
      number       = {29},
      issn         = {0270-6474},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {DKFZ-2023-01303},
      pages        = {5290-5304},
      year         = {2023},
      note         = {2023 Jul 19;43(29):5290-5304},
      abstract     = {The perforant path provides the primary cortical excitatory
                      input to the hippocampus. Due to its important role in
                      information processing and coding, entorhinal projections to
                      the dentate gyrus have been studied in considerable detail.
                      Nevertheless, synaptic transmission between individual
                      connected pairs of entorhinal stellate cells and dentate
                      granule cells remains to be characterized. Here, we have
                      used mouse organotypic entorhino-hippocampal tissue cultures
                      of either sex, in which the entorhino-dentate (EC-GC)
                      projection is present and EC-GC pairs can be studied using
                      whole-cell patch clamp recordings. By using cultures of
                      wildtype mice, the properties of EC-GC synapses formed by
                      afferents from the lateral and medial entorhinal cortex were
                      compared and differences in short-term plasticity were
                      identified. Since the perforant path is severely affected in
                      Alzheimer's disease, we used tissue cultures of
                      amyloid-precursor protein (APP)-deficient mice to examine
                      the role of APP at this synapse. APP deficiency altered
                      excitatory neurotransmission at medial perforant path
                      synapses, which was accompanied by transcriptomic and
                      ultrastructural changes. Moreover, presynaptic but not
                      postsynaptic APP deletion through the local injection of
                      Cre-expressing adeno-associated viruses in conditional
                      APPflox/flox tissue cultures increased the neurotransmission
                      efficacy at perforant path synapses. In summary, these data
                      suggest a physiological role for presynaptic APP at medial
                      perforant path synapses that may be adversely affected under
                      altered APP processing conditions.SIGNIFICANCE STATEMENTThe
                      hippocampus receives input from the entorhinal cortex via
                      the perforant path. These projections to hippocampal dentate
                      granule cells are of utmost importance for learning and
                      memory formation. Although there is detailed knowledge about
                      perforant path projections, the functional synaptic
                      properties at the level of individual connected pairs of
                      neurons are not well understood. In this study, we
                      investigated the role of the amyloid precursor protein (APP)
                      in mediating functional properties and transmission rules in
                      individually connected neurons using paired whole-cell
                      patch-clamp recordings and genetic tools in organotypic
                      tissue cultures. Our results show that presynaptic APP
                      expression limits excitatory neurotransmission via the
                      perforant path, which could be compromised in pathological
                      conditions such as Alzheimer's disease.},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37369586},
      doi          = {10.1523/JNEUROSCI.1824-22.2023},
      url          = {https://inrepo02.dkfz.de/record/277141},
}