Brain-derived neurotrophic factor enhances long-term potentiation in rat visual cortex - PubMed (original) (raw)

Brain-derived neurotrophic factor enhances long-term potentiation in rat visual cortex

Y Akaneya et al. J Neurosci. 1997.

Abstract

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), members of the nerve growth factor (NGF) gene family, have been suggested to play a role in experience-dependent modification of neural networks in the developing nervous system. In this study we addressed the question of whether these neurotrophins are involved in long-term potentiation (LTP) in developing visual cortex. We recorded layer II/III field potentials and whole-cell currents evoked by test stimulation of layer IV at 0.1 Hz in visual cortical slices prepared from young rats (postnatal day 15-25) and observed effects of BDNF, NT-3, and NGF on these responses. Then we analyzed the effects of these neurotrophins on LTP induced by tetanic (Theta-burst type) stimulation of layer IV. We found that BDNF at 200 ng/ml potentiated field potentials and EPSCs in most cases and that this potentiation lasted after cessation of the BDNF application. At the concentration of 20 ng/ml, BDNF did not show such an effect, but it enhanced the magnitude of expressed LTP. On the other hand, NT-3 and NGF had none of these effects. Immunohistochemical staining of slices with antibody against BDNF showed that exogenous BDNF penetrated into the whole slice within approximately 5 min of its application. The actions of BDNF were blocked by preincubation of slices with TrkB-IgG fusion protein, a BDNF scavenger, or coapplication of K252a, an inhibitor for receptor tyrosine kinases. TrkB-IgG or K252a itself completely blocked LTP, suggesting that endogenous BDNF or another TrkB ligand plays a role in LTP in the developing visual cortex.

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Figures

Fig. 1.

Fig. 1.

Potentiation of EPSCs by BDNF. _A,_Examples of EPSCs recorded from a pyramidal cell-like neuron in layer II/III of the cortex before (a), during (b), and after (c) the application of BDNF. Test stimulation was given to layer IV at 0.1 Hz. Membrane potential was clamped at −70 mV. The time when each record was obtained is shown by corresponding letters in B: superimposition of five sweeps. B, _C,_Plots of the peak amplitude and falling slope of EPSCs against time, respectively. The value is expressed as the percentage of the mean of 60 responses before the application of BDNF. D, Plots of the series resistance against time. The time when BDNF was applied to the slice is indicated by a horizontal bar.

Fig. 4.

Fig. 4.

Changes in response amplitude during neurotrophin application. The ordinate represents the ratio of the mean amplitude of field responses (open circles) calculated from 30 responses for 25–30 min or that of EPSCs (filled circles) from 30 responses for 15–20 min after starting the neurotrophin application to that of 60 responses just before the application. Short horizontal bars and vertical bars represent means and twice the SEM for the same group of slices or cells, respectively. The number of slices or cells used for each test is shown at the top of each column.

Fig. 2.

Fig. 2.

Potentiation of field responses by BDNF.A, Examples of field responses of layer II/III to test stimulation of layer IV, recorded at the time points indicated by corresponding letters in B. Arrows_indicate the postsynaptic component of responses. Initial upward (negative) peaks are potentials evoked antidromically by layer IV stimulation. B, C, Plots of the amplitude and rising slope of the postsynaptic component of field potentials against time, respectively. BDNF at 200 ng/ml was applied to the slice during the period indicated by horizontal bar. In_B, the amplitude of the postsynaptic component from the preceding positive (downward) to negative peak was measured and expressed as the percentage of the mean of 60 responses before the application of BDNF. In C, the slope of the rising phase (from 10 to 90% point) of the postsynaptic component was measured and expressed in the same way as in B.

Fig. 6.

Fig. 6.

Enhancement of LTP by BDNF. A, Examples of layer II/III field responses to test stimulation of layer IV, recorded at the time points indicated by corresponding letters in_B_. Other conventions are the same as in Figure2_A_. B, Time course of the amplitude of postsynaptic component of responses to test stimulation of layer IV. Tetanic stimulation was given to layer IV at the time 0, indicated by arrow. The amplitude of responses is calculated as the percentage of the mean of 60 responses before the application of BDNF.

Fig. 3.

Fig. 3.

Time courses of the mean amplitude of field responses. For each slice, the mean of six consecutive responses was calculated as a percentage of that of 60 control responses before the application of BDNF. Vertical bars indicate twice the SEM. Circles without vertical bars indicate that the value of SEM was smaller than that of the radius. A–D, BDNF was applied to slices as indicated by horizontal bars. In A, the _asterisk_indicates that the number of slices during the marked period was six; otherwise the number of slices was 15. In B, slices were preincubated with TrkB-IgG. The number of slices used for each test is shown at the top of each graph.

Fig. 5.

Fig. 5.

Rapid penetration of BDNF into slices. Photomicrographs of sections obtained from slices before (A), during (B), and after (C) perfusion with the medium containing BDNF at the indicated concentration. Scale bars, 1 mm. All of the slices shown here were processed simultaneously in identical staining conditions. Pia is upward and white matter is downward for each slice. In_C_, slices were subjected to immunohistochemistry 30 min after the medium containing BDNF at 20 (left) and 200 (right) ng/ml was changed to the standard medium.

Fig. 7.

Fig. 7.

Time courses of mean amplitude of field responses after tetanic stimulation with or without BDNF, K252a, and TrkB-IgG.Vertical bars indicate twice the SEM for the same group of slices. Circles without vertical bars indicate that the value of SEM was smaller than that of radius. A, Tetanic stimulation was applied to layer IV of the cortex without any drug at the time point indicated by arrow. B, C, D, and F, Time courses of amplitude of responses after tetanus with BDNF and K252a, as indicated by horizontal bars. E, Time course of amplitude of responses after tetanus. In E and F, slices were preincubated with TrkB-IgG. For each slice, the mean of six consecutive responses was calculated as percentage of that of 60 responses just before the application of BDNF (B, F), K252a (C, D), or tetanic stimulation (A, E).

Fig. 8.

Fig. 8.

Ratio of the amplitude of responses 25–30 min after tetanus to that of control responses. Ordinate represents the ratio of mean amplitude of the postsynaptic component of responses calculated from 30 consecutive responses for 25–30 min after tetanus to that of another 60 responses just before tetanus. Short horizontal bars and vertical bars represent means and twice the SEM for the same group of slices, respectively. The number of slices used for each test is shown at the top of each column.tet., Tetanic stimulation; inact. BDNF, inactivated BDNF.

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