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

Lan Guo, Mason L. Yeh, Verginia C. Cuzon Carlson, Erin M. Johnson-Venkatesh, Hermes H. Yeh

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    13 Scopus citations

    Abstract

    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 an terogradely delivered. Here we provide the neuroanatomical substrate for an anterograde hippocam-poseptal 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 levelsthatisdependentonthepatternofintrahippocampalstimulation.Inaddition,weshowthat 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.

    Original languageEnglish (US)
    Pages (from-to)7701-7710
    Number of pages10
    JournalJournal of Neuroscience
    Volume32
    Issue number22
    DOIs
    StatePublished - May 30 2012

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    ASJC Scopus subject areas

    • Neuroscience(all)

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