SYNAPTIC PLASTICITY: PHYSIOLOGY AND NEUROLOGICAL DISEASE - Synaptic Plasticity: New Research - page 14

affinity receptor for NGF, but was subsequently shown to bind each of the neurotrophins with
approximately equal nanomolar affinity [Frade and Barde, 1998; Rodriguez-Tebár et al.,
1998]. In contrast to interactions with p75 NTR , the neurotrophins dimerise the Trk receptors,
resulting in activation through transphosphorylation of the kinases present in their
cytoplasmic domains. Activated neurotrophin Trk receptors trigger three signaling cascades,
phospholipase Cγ-IP 3 , Ras-Raf-ERK, and PI3K, all of which have been implicated in the
varied actions of neurotrophins, ranging from modulation of gene expression, neuronal
morphology, synaptic plasticity, and neurotransmitter release [Segal and Greenberg, 1996;
Chao, 2003; Reichardt, 2006]. The four neurotrophins exhibit specificity in their interactions
with the three members of this receptor family with NGF activating TrkA, BDNF and NT-4
activating TrkB, and NT-3 activating TrkC. In addition, NT-3 can activate the other Trk
receptors with less efficiency [Esposito et al., 2001].
Among the neurotrophins, BDNF in particular is a potent modulator of activity-
dependent synaptic plasticity in the CNS [Akaneya et al., 1997; Poo, 2001] (Fig. 2).
Figure 2. Enhancement of LTP by BDNF. A, Examples of layer II/III field responses to test stimulation
of layer IV, recorded at the time points indicated by corresponding letters in B . Time course of the
amplitude of postsynaptic component of responses to test stimulation of layer IV. Tetanic stimulation
was given to layer IV at time point 0 (arrow). See Akaneya et al. (1997) for further details.
[Reproduced from The Journal of Neuroscience 17(17), Y. Akaneya, T. Tsumoto, S. Kinoshita and H.
Hatanaka, Brain-derived neurotrophic factor enhances long-term potentiation in rat visual cortex, 6707-
6716 (Fig. 6), Copyright (1997), with permission from The Society for Neuroscience].
BDNF acts via Rho GTPases to regulate the assembly of the actin cytoskeleton in
developing neurons [Ozdinler and Erzurumlu, 2001; Gehler et al., 2004], and aspects of these
signaling pathways may be retained into adulthood in hippocampus [Rex et al., 2007].
Indeed, long-term (minutes to hours) exposure to BDNF induces varied effects on