Fig. 2: Deep brain stimulation of medial forebrain bundle evoke noradrenalin release in prefrontal cortex (PFC).

A Timeline of experiment protocol. The rats were first evaluated depressive-like phenotype via the force swim test (FST). During the recording period, six different randomized daily stimulation parameters were used on Days1-6. On the seventh day, the rats were stimulated with 130 Hz 100 us DBS and immediately sacrificed for immunohistochemical examination. DBS, deep brain stimulation. B DBS paradigm: 5 s stimulation was given to examine the acute release of NA and ultrasonic vocalization. The stimulation was repeated 20 times with 50 s interval. C Total immobility time in force swim test between Sprague Dawley (SD, n = 6) and Flinders Sensitive Line (FSL, n = 11) rats; Student’s t-test, t = 3.685, df = 15, P = 0.0022. D Schematic drawing of experiment set up. E Schematic drawing of virus injection/ optic fiber implantation sites in the mPFC (left) and NAC (right) in SD and FSL animals; the DBS electrode implantation (below) in the medial forebrain bundle (mfb) is also shown, and the distribution of the sites is illustrated in more detail (magnification). Dopamine-ß-Hydroxylase (DßH) staining identified the noradrenergic component in the mfb. (F-K) NA release 5 s prior to DBS, 5 s during DBS, and 50 s post-DBS under different conditions and across the experimental groups; (F´-K´) Pre-DBS vs DBS release under different conditions and across the experimental groups. (F, F´) NA release in PFC at 30 Hz 100 μs. (G, G´)130 Hz 100 μs. (H, H´) 30 Hz 250 μs. (I, I´) 130 Hz 250 μs. (J, J´) 30 Hz 350 μs. (K, K´) 130 Hz 350 μs; animal strains versus stimulation condition (pre DBS, −5 - 0 and during DBS, 0 - 5). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Error bars: SEM.