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Fig. 1 | Cell & Bioscience

Fig. 1

From: Sex-dependent neuronal effects of α-synuclein reveal that GABAergic transmission is neuroprotective of sleep-controlling neurons

Fig. 1

α-synM induced an inhibitory outward current and modulated synaptic transmission in LDT neurons in the female. A) (Left) Cartoon schematic of the sagittal mouse brain to show the block of the brain containing the LDT. A LDT coronal brain slice taken from this block is shown below in inset. (A) (Right) Coronal brain slice cartoon modified from [72] to show in greater detail in insets to the sides the location of the LDT (indicated by white arrow in panel to the left). (B) Sample of membrane response to α-synM, which induced inhibitory, outward currents in the female in the LDT (B1). An outward inhibitory current was also elicited in SN neurons (B2). (B) Graphs of holding currents before and after application of α-synM to LDTF and SNF neurons showed a significant increase in positive holding current indicating that α-synM induced outward currents. The amplitude of the outward current evoked by α-synM in LDTF and SNF neurons was not different (LDTF: n = 14, SNF: n = 11; p = 0.3847; Unpaired Student’s T-test) as shown by the plots of the individual amplitude of current induced in both nuclei. Bar chart showing that the proportion of recorded cells responding to α-synM with induction of outward current did not differ significantly between the LDTF and SNF (LDTF: n = 14 sampled/14 responded, SNF: n = 11 sampled/11 responded; p = 1.000; Fisher’s Exact Test). (C) α-synM modulated synaptic events in neurons recorded within LDTF and SNF. (C1- C2) samples of recordings showing frequency of synaptic events in control and in presence of α-synM in both LDTF and SNF. (Rightmost panels) Single sEPSCs (spontaneous excitatory postsynaptic currents) in a LDTF and in a SNF neuron are shown with a high-gain time and amplitude scale under control conditions and in presence of α-synM illustrating the reduction in amplitude in both nuclei when α-synM was present. Data presented in paired plots summarize findings from the population of recorded cells, which revealed that α-synM induced a significant decrease in amplitude of EPSCs in LDTF (n = 5; p = 0.0253; Paired T-test) and SNF neurons (n = 4; p = 0.0483; Paired T-test) and elicited a significant decrease in the frequency of sEPSCs in LDTF neurons (n = 5; p = 0.0475; Paired T-test), which was a change not seen in sEPSCs in the SN (n = 4; p = 0.4735; Paired T-test). LDT: Laterodorsal tegmental nucleus; 4 V: 4th ventricle; IC: Inferior colliculus; DTgP: Dorsal tegmental nucleus, pericentral: DRN: dorsal raphe nucleus; LC: Locus coeruleus; LDTF: Laterodorsal tegmental nucleus of female; SNF: Substantia nigra of female. * Indicates p < 0.05, *** Indicates p < 0.001

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