Fig. 3: Ex-vivo optogenetic stimulation of hippocampal dopaminergic fibres induces a D1/D5 receptor-mediated potentiation of CA3-CA1 synaptic transmission and rescues HFS-LTP in 6-month-old Tg2576 mice. | Translational Psychiatry

Fig. 3: Ex-vivo optogenetic stimulation of hippocampal dopaminergic fibres induces a D1/D5 receptor-mediated potentiation of CA3-CA1 synaptic transmission and rescues HFS-LTP in 6-month-old Tg2576 mice.

From: Optogenetic stimulation of midbrain dopaminergic neurons rescues hippocampal synaptic plasticity deficits in a mouse model of Alzheimer’s disease

Fig. 3

A Schematic representation of optogenetic stimulation of dopaminergic (eYFP+) fibres in the hippocampus of 6-month-old DATCre/WT and DATCre/Tg mice applied during electrical single-pulse or HFS of Schaffer collaterals. Field EPSPs (fEPSPs) were recorded in the CA1 stratum radiatum. B Representative traces of fEPSPs (scale bar: 4 ms; 0.4 mV) from 6-month-old DATCre/WT, DATCre/Tg and DATCre/Tg mice in the presence of 20 μM SCH-23390 elicited in the dorsal hippocampus at half maximal Schaffer collateral stimulation before (1) and 30 min after (2) dopaminergic phasic photostimulation (depicted by the blue vertical band). The plots below show the time-course and pooled data of the average fEPSP slope ( ± s.e.m.) normalized to the mean fEPSP slope pre-stimulation (DATCre/WT: n = 12 slices / 5 mice, Welch’s t-test: ***p = 0.0005; DATCre/Tg: n = 15 slices / 10 mice, Welch’s t-test: ***p = 0.0003, DATCre/Tg SCH23390: n = 4 slices / 3 mice, Welch’s t-test: *p = 0.0275). Empty dots refer to female mice, while full dots to males. C Representative traces (scale bar: 10 ms; 1 mV) showing fEPSPs elicited in the dorsal hippocampus at half maximal Schaffer collateral stimulation in DATCre/WT and DATCre/Tg slices from 6-month-old mice during baseline (1) and 1 h (2) after two HFS trains. The phasic optogenetic stimulation protocol (blue band) was applied just prior to the HFS trains (vertical arrow) in DATCre/Tg slices (Opto mice) and was compared to DATCre/WT and DATCre/Tg mice not receiving photostimulation (Sham mice). The plot below shows the time-course of normalized, average fEPSP slope and the pooled data (DATCre/WT Sham: n = 5 slices / 3 mice; DATCre/Tg Sham: n = 8 slices / 3 mice; DATCre/Tg Opto: n = 11 slices / 4 mice; One-Way ANOVA for treatment and genotype F2,21 = 3.8190, p = 0.0385; DATCre/WT Sham vs DATCre/Tg Sham: **p = 0.0034; DATCre/Tg Sham vs DATCre/Tg Opto: *p = 0.0493 with Sidak’s multiple comparisons test). Empty dots refer to female mice, while full dots to males. [Schematics were created using BioRender (https://biorender.com)].

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