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doi: 10.1242/10.1242/dev.00224

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Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions

¹ AG Entwicklungsneurobiologie ND 6/72, Fakultät für Biologie, Ruhr-Universität, 44780 Bochum, Germany
² Institute for Neurophysiology, CNR, 56100 Pisa, Italy

View larger version (31K): [in a new window]   Fig. 1. Neurotrophins affect LGN neuron size. White bars represent contralateral and black bars ipsilateral values. Size frequency histograms reveal that (A) cortical cytochrome C control and (B) BDNF infusions were not effective. In contrast, (C) cortical NT-4/5 and (D) NGF infusions consistently induced shifts to larger sizes. In the absence of a retrograde tracer all neuronal somata had to be sampled including small-sized cells, which presumably correspond to non-reactive interneurons (representing 20% of LGN neurons) (Sefton and Dreher, 1995). However, the significance levels remained the same when running the tests on only the largest 80% of the neurons. The small insets indicate the median shifts [(ipsilateral median size — contralateral median size)/contralateral median size] in the individual animals analyzed. Positive shifts indicate larger ipsilateral neurons, negative shifts indicates smaller ipsilateral neurons; shifts of up to ±5% were due to biological variation.

View larger version (31K): [in a new window]   Fig. 5. Effects of neurotrophins on soma size in primary visual cortex layer IV neurons, and layer VI neurons given in the small insets. White bars represent contralateral and black bars ipsilateral values. (A) Size frequency histograms reveal that cytochrome C control was not effective. (B) BDNF, however, consistently induced dramatic shifts to larger sizes (MWU-test, ipsi versus contra, P<0.0001). (C) In contrast, NT-4/5 did not induce growth of layer IV neurons (diamonds) and layer VI neurons (circles) during the P20-28 infusions. However, the early P12-20 infusions did result in a significant growth of layer IV (triangles up) and layer VI neurons (triangles down), indicating a developmental time window of responsiveness to NT-4/5. (D) NGF did not evoke any growth. The small insets indicate the percentage of median shift in the individual animals analyzed. At P20-28, only the values for BDNF infused animals differed from controls (one way ANOVA, Tukey's post hoc test).

View larger version (31K): [in a new window]   Fig. 2. NT-4/5 accelerates growth of LGN neurons. White bars represent contralateral and black bars ipsilateral values. Size frequency histograms reveal that cortical NT-4/5 infusions (A) at the beginning and (B) at the peak of the critical period consistently induced shifts to larger sizes. (C,D) When (C) early and (D) late infusion periods were followed by survival to P45, the contra- and the ipsilateral population showed the same size variation and for both sides the peaks occurred at larger sizes than in the younger animals. The small insets indicate the median shifts in the individual animals analyzed.

View larger version (9K): [in a new window]   Fig. 3. Cortical neurotrophins accelerate development of LGN neurons. Medians of contralateral (white circles) and ipsilateral (black circles) LGN were compared at P20 (NT-4/5, n=2), and P28 (NT-4/5 and NGF, total n=7) and at P45 (NT-4/5, combined n=4 plus n=2 untreated P45 animals). NT-4/5 and NGF data were pooled, because both factors elicited the same highly significant size shifts (compare Fig. 1C with 1D). Contralateral somata progressively reach the adult size whereas ipsilateral somata reach adult sizes prematurely because of NT-4/5 and NGF infusions.

View larger version (22K): [in a new window]   Fig. 4. Cortical neurotrophins regulate soma size in the SC. White bars represent contralateral and black bars ipsilateral values. The small insets indicate the percentage of median shifts in the individual animals: diamonds represent the total SGS neuron population, and circles the CB immunoreactive neuron population. Size frequency histograms reveal that (A) cortical cytochrome C control was not effective (MWU-test ipsi versus contra P>>0.05 in all animals tested for both populations). (B) NT-4/5 however consistently induced shifts to larger the sizes in the total SGS neuron population (MWU-test P<0.0001 in all animals tested). (C) In contrast, BDNF infusions consistently induced shifts to smaller sizes in the total SGS neuron population. The median shifts for SGS neurons (diamonds in the insets) are significantly different from cytochrome C values (one way ANOVA P<<0.05, Tukey's post hoc test). The CB neurons (circles in the insets) did not undergo size shifts (one way ANOVA, Tukey's post hoc test).

View larger version (15K): [in a new window]   Fig. 6. Size variation of cortical layer IV and LGN neurons in wild-type (WT) and synRAS-TG mice. White bars represent wild-type and black bars synRAS-TG values. (A) Layer IV neurons were consistently larger in the synRAS-TG mice (MWU-test, WT versus TG, P<0.0001). (B) However, there was no consistent trend to larger sizes in LGN neurons indicating that they do not adjust with larger sizes to the hypertrophic cortical neurons which develop postnatally in synRAS-TG mice. The small inset indicates the percentage of median shift observed in the five sibling pairs aged P40 and 3 months (diamonds) and in the three sibling pairs aged P13 and P30 (circles).

View larger version (32K): [in a new window]   Fig. 7. LIF transiently delays somatic growth of LGN, visual cortex and SGS neurons. White bars represent contralateral and black bars ipsilateral values. The small insets indicate the percentage of median shift in the individual animals analyzed. (A) After P12-20 LIF infusions ipsilateral LGN neurons were consistenly shifted to smaller sizes (MWU-test, ipsi versus contra, P<0.0001). (B) However, during a survival period until P45, ipsi- and contralateral LGN neurons had aquired the same adult size variation, and like NT-4/5 (Fig. 2A,C) the P45 peaks occurred at larger sizes than at P20. (C) Furthermore, LIF severely affects growth of primary visual cortex layer IV (diamonds) and layer VI neurons (triangles; MWU-test ipsi versus contra P<0.0001 for both populations). (D) LIF affects SGS neurons, which were consistently smaller on the infused hemisphere. This was true for the total SGS neurons (diamonds) and for the tectothalamic CB neurons (circles; significant difference to cytochrome C, one way ANOVA P<<0.05, Tukey's post hoc test). The growth delay is transient, because after survival to P45 some size distribution has recovered (total SGS neurons at P45 represented by triangles up, and CB neurons at P45 by triangles down).

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