Enhancements in mossy fibers long‐term potentiation (LTP) are neurotrophin‐specific.

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In addition to a clearly defined role of BDNF (Brain‐derived neurotrophic factor) in cell survival and differentiation, this neurotrophin has recently been implicated in hippocampal plasticity, including LTP. Interestingly, the mossy fiber projection to pyramidal cells in area CA3 of the hippocampus contains the highest concentration of BDNF in the CNS (Danzer and McNamara, 2004). Also, BDNF administration results in CA3 hyperexcitability in response to mossy fiber stimulation (H.E. Scharfman et al. 1996). BDNF dramatically enhances mossy fiber field potentials and LTP in vitro (Jiménez et al 08). In vivo BDNF infusions enhance mossy fiber LTP and result in neurogenesis at the mossy fiber synapse (Gomez‐Palacio‐Schjetnan and M. Escobar et al., 2008). Previous work found that BDNF mRNA is upregulated in the hippocampus following in vivo mossy fiber LTP (Thompson et al. 2003). In this study we addressed the question of whether other neurothrophins such as NT3 and NGF are involved in LTP at the mossy fiber synapse. Using a hippocampal slice preparation, we recorded field potentials at CA3 pyramidal cells following high frequency stimulation (HFS; 2 trains 100 Hz, 1 sec duration) of the mossy fiber pathway, and observed the effects of bath application of BDNF (concentration 200 ng/ml). In addition, we recorded field potentials at CA3 pyramidal cells following HFS of the mossy fiber pathway and observed the effects of micropipette application of NT3 (200ng/ml), a tyrosine kinase C (trkC) activator, and NGF (200ng/ml), a tyrosine kinase A (trkA) activator. We found that BDNF alone resulted in mossy fiber LTP, and this effect was further enhanced if BDNF was bath applied prior to HFS whereas enhancement of LTP was not observed following application of NGF or NT3. Our results indicate that BDNF plays a specific role on synaptic plasticity and LTP at the mossy fiber synapse.Supported by: RCMI (8G12MD007579–27), MBRS‐RISE program (NIH‐NIGMS: R25GM082406)