Fig. 1
Experimental design showing timeline and corresponding figure numbers. A A guide cannula was implanted for icv. drug administration on the left ventricle (histologic verification image on the right). A minimum of 8 days after surgery, a single injection of either Aβ1–42 or controls (reverse Aβ42–1 peptide or vehicle), were administered. Scale bars: 500 μm. B Habituation phase of Barnes maze task was conducted the day before icv. administration (day-1). 1 h after treatment injection (day 0, pre-training icv. injection), training in the Barnes maze began, which consisted of 3 trails per day for 4 consecutive days (days 0–3). Two memory tests were conducted, on days 7 and 11 post-injection. C The Open field habituation test was conducted on days 15 and 16 post-injection. D Finally, mice went through a test battery that included testing of stereotyped and locomotor behaviors by an automated LABORAS® System to assess their overall spontaneous behavior and health, as well as rotarod, elevated plus maze and tail suspension tests (days 15–17). E Another cohort of animals was used to evaluate the effect of Aβ1–42 on ex vivo hippocampal LTP by multi-electrode arrays (MEAs) electrophysiology (days 1–17 post-injection). Representative location of stimulation (St., green) and recording (Rec., red) electrodes in an hippocampal coronal slice. F A different cohort of animals underwent the Object location memory test (OLM) to study the effect of Aβ1–42 on memory retrieval. After habituation (day 0), both training and retrieval (OLM1) sessions were conducted on day 1. On day 2, animals were icv. injected with the corresponding treatment (post-training injection) and, 1 h later, another retrieval session (OLM2) was performed. G The same animals also underwent the Open field habituation test, with post-training icv. treatment. D, dorsal; DG, dentate gyrus; icv., intracerebroventricular; L, lateral; V, ventricle; M, medial