Fig. 5: Dat1+ neurons residing in the PeVN modulate locomotion.
From: A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice
a Chemogenetic stimulation of periventricular Dat1+ neurons led to an increase in locomotor activity during the dark phase (n = 7 animals, CT: 12:00-18:00) when infected with and stimulated by an AAV encoding hM3D(Gq) and subsequent exposure to CNO. One-sided paired t-test was used to assess statistical significance in response to CNO administration. P values at night are 0.0001, 0.016, 0.012, 0.019 for “Distance moved, “Walking duration”, “Wheel running counts” and “Activity”, respectively. b Chemogenetic inhibition of periventricular Dat1+ neurons significant reduced locomotion during both the dark (CT: 12:00–18:00) and light (CT: 00:00–06:00) phases (n = 7 mice). Dat1+ neurons in the PeVN were infected with an AAV encoding hM4D(Gi) and subsequently stimulated with CNO. One-sided paired t-test was used to assess statistical differences in CNO administration. P values are 0.0049, 0.0136, 0.0128, 0.0010 during the day for “Distance moved, “Walking duration”, “Wheel running” and “Activity”, respectively. For the dark period, respective p values for “Walking duration”, “Wheel running counts” and “Activity” are 0.0285, 0.0016, 0.0201. c Combinatorial chemogenetic experiments involving the simultaneous metabotropic activation of Dat1+ neurons in the PeVN and inhibition of LS neurons significantly reduced locomotion (orange rectangles, n = 5) as compared to when only activating Dat1+ neurons (red circles) to compensate for the inhibitory effect of the reduced activity of LS neurons (green triangles, n = 6). during the dark phase (CT: 12:00–18:00). One-way ANOVA with the Student–Newman–Keuls method for pairwise multiple comparisons was used returning p values as 0.004 (**), 0.001 (***). d Schematic illustration of functionally diverse LS neuron pools and their connectivity based on their differential pharmacological responses in Ca2+ imaging experiments. ***p < 0.001; **p < 0.01, *p < 0.05. We used Biorender for the design of experimental schemes and anatomical drawings (in a–c).
