Dopamine and BDNF Modulate LTP in the BLA Figure 11. BLA projection neurons co-express mRNA and protein for D1- and TrkB receptors, as well as MMP17. A-A0) Photomicrographs showing the high level of co-localization for TrkB (A, red) and CaMKIIa- (A9, green) immunoreactivity in putative principal neurons of the BLA (A0, merged, double arrows). Note, a subpopulation of TrkB-positive neurons do not co-localize CaMKIIa (A0, open arrows, merged). B-B0) Photomicrographs showing the high level of co-localization for MMP17 (B, red) and CaMKIIa- (B9, green) immunoreactivity in BLA neurons (B0, merged, double arrows). Note, a subpopulation of MMP17-positive neurons do not co-localize CAMKIIa. C-C0) Photomicrographs showing the co- localization of MMP16 (C, red) and CaMKIIa (C9, green) immunoreactivity in BLA neurons (C0, merged, double arrows). Note, a subpopulation of CAMKIIa-positive neurons do not co-localize MMP16. All photomicrographs were taken from the basolateral nucleus of the BLA. In all images magnification = 63x, scale bar = 10 mm. C) Photograph of an agarose gel showing the typical mRNA expression pattern for a D1- and D5- mRNA- positive principal neuron. The associated table shows the relative expression of D1, D5, TrkB, MMP17 and ERK1/2 mRNA expression in single BLA principle neurons. doi:10.1371/journal.pone.0026065.g011 prevent the conversion of proBDNF to mBDNF and subsequent activation of TrkB receptors. Consistent with this observation MMPs have been shown to play a key role in facilitating synaptic plasticity in the hippocampus and prefrontal cortex [54,55]. Importantly, our immunohistochemical and single cell RT-PCR study revealed that principal neurons that express D1 and D5 receptor mRNA also show high protein expression for both membrane-type matrix metalloproteinase 16 and 17 (MMP16, MMP17), as well as the TrkB receptor. It is possible that either MMP16 or MMP17 and the TrkB receptor may be co-localized in the spines of principal neurons to facilitate BDNF-induced modulation of sensory input. LTP could be induced in almost all of the projection neurons that we recorded and, hence, MMP16 and MMP17 may serve the same function in different populations of principal neurons. Moreover, principal neurons of the BLA may be capable of differentially expressing multiple subtypes of MMPs, each of which could facilitate LTP induction. Finally, principal neurons of the BLA also have a random spatial orientation and an extensive, overlapping, dendritic arbor. Following HFS, zinc released from presynaptic cortical terminals may activate MMPs in those neurons that express them, which could, in turn, modulate the conversion of proBDNF to mBDNF even at synaptic contacts where the postsynaptic neuron does not express MMPs. Thus zinc release from limbic afferents may ensure input specificity for LTP induction but may also allow generalization of the response to clusters of neighboring principal neurons. PLoS ONE | www.plosone.org 12 October 2011 | Volume 6 | Issue 10 | e26065