overall goal of this proposal is to examine the role of the neurotrophin
brain-derived neurotrophin factor (BDNF) on hippocampal functioning.
BDNF is well-characterized as a regulator of neuronal growth and
survival, and it plays an important role in both short and long-term
plasticity at NMDA-dependent synapses in the hippocampus. Recent
evidence suggests that BDNF also modulates plasticity at non-NMDA
dependent synapses, yet the mechanisms underlying this modulation are
not clear. In this proposal we will examine the role of BDNF on
plasticity at the NMDA-independent mossy fiber-CA3 (MF-CA3) pathway of
the hippocampus. The central hypothesis is that BDNF results in enhanced
MF-CA3 long term potentiation (LTP), and improved hippocampal learning.
In Specific Aim 1, we will characterize the effects of BDNF on mossy
fiber-CA3 LTP in vitro. In Specific Aim 2, we will determine the effect
of BDNF on calcium influx at the mossy fiber-CA3 synapse. Specific Aim 3
will characterize the role of endogenous BDNF on hippocampal learning.
Specific Aim 4 will determine the effect of intrahippocampal BDNF
infusions on hippocampla learning. Our proposed research is clinically
relevant because understanding the role of growth factors, such as BDNF,
on hippocampal plasticity during learning could lead to interventions to
augment hippocampal functioning.