Fig. 1: Midbrain 6-OHDA causes loss of DA in the dorsal hippocampus, inducing LTP and behavioural deficits in 3-month-old mice.

A 2-month-old C57BL/6N mice were unilaterally infused in the midbrain with 6-OHDA or Saline. 30 min before stereotaxic injection, mice received an i.p injection of the NE reuptake inhibitor desipramine. Mice were used for experimental sessions 1 month after the midbrain lesion. B Representative coronal sections of the midbrain, showing immunofluorescence for TH⁺ neurons in Saline and 6-OHDA 3-month-old mice (scale bar: 500 µm), and stereological TH⁺ cell count in the ipsilateral VTA (n = 4 mice / group. Welch’s t-test: ****p < 0.0001) and SNpc (n = 4 mice / group. Unpaired t-test: ****p < 0.0001). C Confocal images and plots showing TH⁺ fibre density in the ipsilateral dorsal hippocampal (expressed as fibres / 250 μm; scale bar: 50 µm) in 3-month-old Saline and 6-OHDA mice (n = 4 mice / group. Unpaired t-test: ***p = 0.0002). Nuclei are counterstained with DAPI. D Schematic representation of the experimental procedure for HPLC analysis of total hippocampal levels of DA, NE and relative metabolites in the ipsilateral hippocampus from 3-month-old Saline and 6-OHDA mice. The plots show tissue levels of DA, DOPAC and HVA, expressed as pg in 20 μL of supernatant (n = 5 mice / group. DA: Unpaired t-test: *p = 0.0294; DOPAC: Unpaired t-test: *p = 0.0242; HVA: Unpaired t-test: **p = 0.0022). E Representative traces showing fEPSPs elicited in the dorsal hippocampus at half maximal Schaffer collateral stimulation in acute slices from 3-month-old Saline and 6-OHDA mice during baseline (1) and 1 h (2) after two HFS trains (scale bar: 2 ms; 0.2 mV). The plots on the right show the time-course of normalized, average fEPSP slope ( ± s.e.m.) and the pooled data (Saline: n = 11 slices / 3 mice; 6-OHDA: n = 12 slices / 4 mice. Unpaired t-test: *p = 0.0243). The vertical arrow indicates the timing of the HFS protocol. Empty dots refer to female mice, while full dots to males. F Graphical representation of the training and test (24 h later) phases of the NOR test performed for 3-month-old Saline and 6-OHDA mice, and plots showing the exploration time spent with the left/right and old/new object during the training and test, respectively (n = 15 mice / group; for Saline, Paired t-test: **p = 0.0025). [Schematics were created using BioRender (https://biorender.com)].