Fig. 5.
Artificial suppression of hippocampal brain-derived neurotrophic factor signaling impaired hippocampal synaptic plasticity and memory. Microinjection of TrkB-Fc (tropomyosin receptor kinase B–Fc) chimera (a recombinant extracellular domain of human tropomyosin–related kinase receptor type B fused to the Fc region of human IgG; 2 μg × 7 days) into the hippocampal CA1 in naïve rats significantly extended the escape latencies (A, n = 10 rats in each group, effect of group [F1, 18 = 13.6, P = 0.0017], effect of time [F4, 18 = 48.6, P < 0.0001], interaction between group and time [P = 0.2]) and shortened the time spent in the target quadrant (B, n = 10 rats in each group, Kruskal-Wallis statistic = 7.41, P = 0.0065) in the Morris water maze test. (B) Representative path tracings in each quadrant during the probe trial on day 6 (T, target quadrant; R, right quadrant; O, opposite quadrant; L, left quadrant). Significantly impaired high-frequency stimulation-induced long-term potentiation of excitatory postsynaptic current (EPSC) was also observed in the hippocampal CA1 neurons in the naïve rats injected with Trkb-Fc chimera ([C, n = 10 neurons from five rats in each group, F1, 18 = 17.42, P = 0.0006], effect of time [P = 0.94], interaction between group and time [P = 0.22]). Microinjection of Trkb-Fc chimera also significantly decreased hippocampal synaptic density (D, n = 5 rats in each group, t = 13.5, DF = 8, two-tailed P < 0.0001, scale bar = 0.25 μm) and dendritic spine numbers (E, n = 5 rats in each group, t = 10.0, DF = 8, two-tailed P < 0.0001, scale bar = 10 μm) in naive rats. Total synapse density was calculated as the number of synapses per 100 μm2 of neuropil. *P < 0.05; **P < 0.01; ***P < 0.001. Data represent mean ± SD.