The amyloid precursor protein regulates synaptic transmission at medial perforant path synapses

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 s..., Ethics statement
Mice were maintained in a 12-hour light/dark cycle with food and water available ad libitum. Every effort was made to minimize distress and pain of animals. All experimental procedures were performed according to the German animal welfare legislation and approved by the animal welfare committee and/or the animal welfare officer at the Goethe-University Frankfurt, Faculty of Medicine, and the Albert-Ludwigs-University Freiburg, Faculty of Medicine.
Preparation of organotypic tissue cultures 
Entorhino-hippocampal tissue cultures were prepared at postnatal day 4 - 5 from C57BL/6J and APP-deficient (APP-/-; null allele; (Li et al., 1996; Heber et al., 2000)) animals of either sex as previously described (Del Turco and Deller, 2007). Briefly, the dorsal brain surface was immobilized on cutting plates with Histoacryl® (B. Braun) and transverse sectioning was performed using a vibratome (Leica, VT1200S). The entorhino-hippocampal complex was dissected from 300 µm transverse..., Data were statistically analyzed using GraphPad Prism 9 (GraphPad software, USA).