Nerve growth factor in the hippocamposeptal system: evidence for activity-dependent anterograde delivery and modulation of synaptic activity.
Nerve growth factor in the hippocamposeptal system: evidence for activity-dependent anterograde delivery and modulation of synaptic activity.
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DOI：
10.1523/jneurosci.0028-12.2012
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发表时间：
2012-05-30
期刊：
影响因子：
--
通讯作者：
Yeh HH
中科院分区：
文献类型：
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作者：
Guo L;Yeh ML;Cuzon Carlson VC;Johnson-Venkatesh EM;Yeh HH
Neurotrophins have been implicated in regulating neuronal differentiation, promoting neuronal survival, and modulating synaptic efficacy and plasticity. Depending on the target and mode of action, the prevailing view is that most neurotrophins can be trafficked and released either anterogradely or retrogradely in an activity-dependent manner. However, the prototypic neurotrophin, nerve growth factor (NGF), is not thought to be anterogradely delivered. Here we provide the neuroanatomical substrate for an anterograde hippocamposeptal transport of NGF by demonstrating its presence in mouse hippocampal GABAergic neurons and in their hippocamposeptal axons that ramify densely and abut neurons in the medial septum/diagonal band of Broca (MS/DB). We also demonstrate an activity-dependent increase in septal NGF levels that is dependent on the pattern of intrahippocampal stimulation. In addition, acute exposure to NGF, via activation of TrkA, attenuated GABAA receptor-mediated inhibitory synaptic currents and reduced sensitivity to exogenously applied GABA. These acute actions of NGF display cell type and functional selectivity, insofar as (1) they were found in cholinergic, but not GABAergic MS/DB neurons, and (2) glutamate-mediated excitatory synaptic activity as well as AMPA-activated current responses were unaffected. Our results advocate a novel anterograde, TrkA-mediated NGF signaling in the central nervous system.
