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Publication : Nerve growth factor in the hippocamposeptal system: evidence for activity-dependent anterograde delivery and modulation of synaptic activity.

First Author  Guo L Year  2012
Journal  J Neurosci Volume  32
Issue  22 Pages  7701-10
PubMed ID  22649248 Mgi Jnum  J:255092
Mgi Id  MGI:6099427 Doi  10.1523/JNEUROSCI.0028-12.2012
Citation  Guo L, et al. (2012) Nerve growth factor in the hippocamposeptal system: evidence for activity-dependent anterograde delivery and modulation of synaptic activity. J Neurosci 32(22):7701-10
abstractText  Neurotrophins have been implicated in regulating neuronal differentiation, promoting neuronal survival, and modulating synaptic efficacy and plasticity. The prevailing view is that, depending on the target and mode of action, 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, we show that acute exposure to NGF, via activation of TrkA, attenuates GABA(A) receptor-mediated inhibitory synaptic currents and reduces 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 CNS.
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