, 2006) or the transfection of cells in a culture dish with constructs that limit synaptic vesicle release and hence leave postsynaptic targets that receive both chronically “silenced” and normal terminals (Béïque et al., 2011, Harms and Craig,

2005, Hou et al., 2008 and Lee et al., 2010). The results of studies on ssHSP have been varied, but some groups indicate a compensatory increase in the expression of AMPARs exclusively at the chronically silenced synapses and not at nearest normal neighbor synapses (Lee click here et al., 2010, Hou et al., 2008 and Béïque et al., 2011). Until now, no group has managed the difficult technical feat of persistently activating single synapses among normal neighbors on a given neuron. Action potential firing and synaptic vesicle release from a single presynaptic neuron can be induced by current injection after whole-cell configuration has been achieved in patch-clamp electrophysiology. However, achieving stable firing for a prolonged period in the activated neuron and determining the synapses coming from the activated cell onto a receiving cell are technically difficult. An alternative strategy is therefore needed to elicit sustained yet selective presynaptic activity. In order to persistently activate some of the axon terminals in a neuronal culture, Hou

and colleagues transfected light-activated glutamate receptor 6 (LiGluR) subunits sparsely into cultured cortical neurons. LiGluR Sirolimus subunits form a normal cation-permeant channel, which is activated only when UV light (380 nm) photoconverts the tethered agonist MAG and is inactivated Ketanserin when blue light (480 nm) catalyzes the reverse isomerization (Szobota et al., 2007). Thus, LiGluR enables light-controlled depolarization, action potential firing, Ca2+ rises, and consequent glutamate release from axonal terminals just in activated neurons.

Due to the low transfection efficiency in the system created by Hou and colleagues, only a few neurons in each dish expressed LiGluR. This ensured that some cells received synaptic input from both light-controlled terminals from LiGluR-expressing neurons and normal terminals from non-LiGluR-expressing neurons. To distinguish the light-controlled terminals from the normal terminals, the authors introduced yellow fluorescent protein-labeled synapsin1 (syn-YFP) to the cells expressing LiGluR (Figure 1). This approach was designed to enable comparison between persistently activated synapses and normal neighbors on the same postsynaptic cell. The method of Hou and colleagues contrasts with a recent study using a different light-activated channel that showed that persistently exciting a single neuron of interest leads to homeostatic postsynaptic changes on that same neuron (Goold and Nicoll, 2010).