Brain‐derived neurotrophic factor blocks long‐term depression in solitary neurones cultured from rat visual cortex

Autor: Fumitaka Kimura, Tadaharu Tsumoto, Nobuaki Taniguchi, Eiji Kumura
Rok vydání: 2000
Předmět:
Zdroj: The Journal of Physiology. 524:195-204
ISSN: 1469-7793
0022-3751
DOI: 10.1111/j.1469-7793.2000.t01-2-00195.x
Popis: To address questions of whether long-term depression (LTD) in the visual cortex is expressed in pre- or postsynaptic sites, whether brain-derived neurotrophic factor (BDNF) exerts its LTD-blocking action without involvement of GABAergic inhibition, and whether the action of BDNF is pre- or postsynaptic, we observed excitatory postsynaptic currents (EPSCs) from solitary neurones cultured on glial microislands. In this preparation GABAergic inhibition is not involved and a group of synapses (autapses) which generate evoked EPSCs is thought to be the same as those generating spontaneous EPSCs. A short depolarising voltage step to the soma generated Na+ spikes which were followed by autaptic EPSCs. When this somatic activation was paired with prolonged depolarisation for 100 ms to −30 mV and repeated at 1 Hz for 5 min, LTD was induced in all of the nine cells tested. Then, the frequency of spontaneous EPSCs decreased, but the amplitude did not change, suggesting that the site of LTD expression is presynaptic. Application of BDNF at 50 ng ml−1 blocked the depression of evoked EPSCs and the decrease in the frequency of spontaneous EPSCs. An inhibitor for receptor tyrosine kinases, K252a, antagonised the action of BDNF, suggesting an involvement of BDNF receptors, TrkB. These results suggest that BDNF prevents low-frequency inputs from inducing LTD of excitatory synaptic transmission through presynaptic mechanisms in the developing visual cortex. Long-term depression (LTD) of synaptic transmission, a counterpart of long-term potentiation (LTP), can be induced in the developing visual cortex (Tsumoto & Suda, 1979; Artola & Singer, 1990; Kirkwood et al. 1993) and is supposed to provide a basis for experience-dependent modifiability of visual cortical neurones during the critical period of postnatal development (Tsumoto, 1992; Singer, 1995; Katz & Shatz, 1996). In contrast to LTP, however, mechanisms underlying LTD have not been fully explored in the developing visual cortex. For example, there has been no systematic approach to the classical, pre- versus postsynaptic issue, although there is a short report suggesting the presynaptic expression of LTD (Torii et al. 1997). To address such an issue, cortical slice preparations in which most studies have been carried out in the past two decades are not always appropriate, because activation of single input fibres, which is necessary for a precise analysis, is extremely difficult and the origins of spontaneous synaptic events which are to be analysed simultaneously with evoked synaptic activities are not necessarily the same as those of the latter. To overcome these difficulties, we used solitary neurones in culture obtained from visual cortex of neonatal rats (Furshpan et al. 1976; Bekkers & Stevens, 1991; Segal, 1991; Kimura et al. 1997). In this sort of preparation we could easily activate a single presynaptic cell which is also postsynaptic, and could record spontaneous and evoked synaptic (autaptic) activities which originate from the same group of synapses (autapses). A class of neurotrophins, brain-derived neurotrophic factor (BDNF), has been reported to enhance excitatory synaptic transmission in various nervous systems and further to play a role in LTP in hippocampus and developing visual cortex (Lohof et al. 1993; Lesmann et al. 1994; Kang & Schuman, 1995; Korte et al. 1995; Levine et al. 1995; Figurov et al. 1996; Stoop & Poo, 1996; Patterson et al. 1996; Akaneya et al. 1997; Carmignoto et al. 1997; Scharfman, 1997; Lesmann & Heumann, 1998; Li et al. 1998; for reviews see Thoenen, 1995; Cellerino & Maffei, 1996; McAllister et al. 1999). In the visual cortex of young rats it has been reported that BDNF blocks the induction of LTD of excitatory synaptic transmission which otherwise is induced by low-frequency stimulation (LFS) of afferents at 1 Hz for 10–15 min (Akaneya et al. 1996; Huber et al. 1998; Kinoshita et al. 1999). There is a possibility, however, that such an LTD-blocking action of BDNF might be due not to direct action on excitatory transmission but to indirect action through a blockade of inhibition, because BDNF was reported to suppress GABAergic inhibitory transmission rather than to enhance excitatory transmission in hippocampus (Tanaka et al. 1997; Frerking et al. 1998) and inhibition is suggested to be involved in the induction of LTD (Artola & Singer, 1990; see Tsumoto, 1992). To test this possibility and further to address the question of whether the site of the LTD expression and of the LTD-blocking action of BDNF is pre- or postsynaptic, we used preparations of excitatory solitary neurones in which GABAergic inhibition is not involved and spontaneous activities are generated at the same synapses (autapses) as those of evoked activities. We found that LTD of excitatory transmission is induced probably through presynaptic mechanisms, and that BDNF prevents LFS from inducing LTD by a direct action on excitatory synapses. Some of the results in this paper have been presented in abstract form (Kumura et al. 1999).
Databáze: OpenAIRE
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