library_construction_protocol: For the analysis of the transcriptome of PV-positive interneurons, animals at the age of 23 weeks were sacrificed by cervical dislocation and decapitated. The brain was quickly removed with sterile instruments and placed in Greys Balanced Salt Solution with glucose (GBSS/Glc: 137.93 mM NaCl, 3.66 mM KCl, 2.702 mM NaHCO3, 1.03 mM CaCl2, 0.28 mM MgSO4x7H2O, 0.84 mM Na2HPO4, 0.22 mM KH2PO4, 5.56 mM glucose; pH 7.4; sterile filtered) on ice. The cortex and the hippocampus were dissected in GBSS/Glc on ice. The tissue was cut into small pieces (1  2 mm3) with a sterile razor blade and transferred into falcons in a sterile environment. After washing (gentle shaking; wash medium 98.2 ml HBSS w/o Ca and Mg; 700 l 1M HEPES; 1 ml Penicillin-Streptomycin; 100 l 65 % glucose) the tissue was incubated for 5 min with 0.25 % Trypsin/EDTA (Thermo Fisher Scientific; 4.5 ml 0.25 % Trypsin/EDTA, 50 l Penicillin-Streptomycin, 50 l 1M HEPES, 500 l 50% trehalose) for 30 min at 37C. Pre-incubated DNAse (AplliChem, 50 l, 4 g/l, 600 U) was added to the mix. A washing step with 2.1 ml trypsin stop-medium (40 ml DMEM/F12, 5 ml FBS, 500 l Penicillin-Streptomycin, 5 ml 50 % trehalose) led to the inactivation of trypsin. 900 l collagenase type 2 (Worthington, 10 mg/ml in HBSS) was added to the medium and the tissue was incubated again for 25 min at 37C. After another washing step with warm trypsin stop-medium and 3.63 l 0.5 M EDTA, the samples were left on ice to cool down and finally resuspended in 1.5 ml trypsin stop-medium. Sterile coated (Sigmacote) Pasteur pipettes with three different opening diameters (large, medium and small) were used to homogenize the tissue (pipetted up and down max 20 times). The lysate was centrifuged at 4C (5 min, 160 rcf) and resuspended in 4 ml wash-buffer/trehalose (36 ml HBSS w/o Ca and Mg, 280 l 1M HEPES, 400 l Penicillin-Streptomycin, 40 l 65 % Glucose, 4 ml 50 % trehalose). After another centrifugation step (4C, 5 min, 160  rcf), the pellet was resuspended in 4 ml 30 % Percoll (GE Healthcare, 7.5 ml Percoll, 15 ml PBS, 2.5 ml 50 % trehalose) for a density gradient centrifugation (4C, 13 min, 600 rcf). The supernatant and the cell waste were discarded in order to resuspend the pellet in 1.0 ml wash-buffer/trehalose. Pellets were resuspended in 1.0 ml wash-buffer/trehalose and sorted. Cell suspensions prepared from the cortical hemispheres and hippocampi of 23-week-old mice were subjected to FACsorting. Following addition of DAPI, cells were sorted using an ARIA III FACS sorter (BD Biosciences, United States) with a maximal flow rate of six. The tdTomato reporter was excited by a laser (excitation 554 nm, emission 581 nm). Living cells were sorted based on a distinctive tdTomato signal. Two populations were sorted: tdTomato-positive (+) cells and tdTomato-negative (-) cells. The different cell populations (Co-tomato+; Co-tomato-; HC-tomato+; HC-tomato-) were collected in 1xPBS with 2 % FBS and centrifuged (4C; 10 min; 1000 g). The supernatant was discarded and the cells were lysed in 150 l TRIzol Reagent (Thermo Fisher Scientific) and then frozen (-80 C) for further processing. RNA was isolated and purified using the Direct-zol RNA MicroPrep Kit from Zymo Research. All samples were processed according to the manufacturers protocol and checked for integrity by capillary gel electrophoresis (Bioanalyzer, Agilent Technologies, Inc., United States). The RNA samples were stored at -80C. Total RNA of cells and native controls were used in biological triplicates to perform whole transcriptome analysis. Library preparation for RNA-Seq was performed using the SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Takara, Cat# 634412) including rRNA-depletion and further processed according to the manufacturers protocol. The concentrations of final cDNA libraries were determined using the Qubit 2.0 fluorometer (Invitrogen) (average 20 ng/l) and quality checked with a Bioanalyzer (Agilent 2100 Bioanalyzer) high sensitivity DNA assay.