TY - JOUR
T1 - Nerve growth factor in the hippocamposeptal system
T2 - Evidence for activity-dependent anterograde delivery and modulation of synaptic activity
AU - Guo, Lan
AU - Yeh, Mason L.
AU - Cuzon Carlson, Verginia C.
AU - Johnson-Venkatesh, Erin M.
AU - Yeh, Hermes H.
PY - 2012/5/30
Y1 - 2012/5/30
N2 - 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.
AB - 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.
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U2 - 10.1523/JNEUROSCI.0028-12.2012
DO - 10.1523/JNEUROSCI.0028-12.2012
M3 - Article
C2 - 22649248
AN - SCOPUS:84861639804
SN - 0270-6474
VL - 32
SP - 7701
EP - 7710
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 22
ER -