Hebbian Plasticity Guides Maturation of Glutamate Receptor Fields In Vivo

Abstract

Synaptic plasticity shapes the development of functional neural circuits and provides a basis for cellular models of learning and memory. Hebbian plasticity describes an activity-dependent change in synaptic strength that is input-specific and depends on correlated pre- and postsynaptic activity. Although it is recognized that synaptic activity and synapse development are intimately linked, our mechanistic understanding of the coupling is far from complete. Using Channelrhodopsin-2 to evoke activity in vivo, we investigated synaptic plasticity at the glutamatergic Drosophila neuromuscular junction. Remarkably, correlated pre- and postsynaptic stimulation increased postsynaptic sensitivity by promoting synapse-specific recruitment of GluR-IIA-type glutamate receptor subunits into postsynaptic receptor fields. Conversely, GluR-IIA was rapidly removed from synapses whose activity failed to evoke substantial postsynaptic depolarization. Uniting these results with developmental GluR-IIA dynamics provides a comprehensive physiological concept of how Hebbian plasticity guides synaptic maturation and sparse transmitter release controls the stabilization of the molecular composition of individual synapses.

Channelrhodopsin-2–XXL, a powerful optogenetic tool for low-light applications

“…As previously reported, ChR2-wt localization was restricted to motor neuron cell bodies under these conditions (28). In contrast, ChR2-XXL displayed strong expression in the efferent nerves leaving the ventral nerve chord (VNC) (Fig.…”

“…Whereas ChR2-wt can be used in translucent larvae fed high concentrations of retinal (24,27,28), it functions inefficiently in central brain neurons of intact adult flies (however, for examples of sensory neurons, see refs. 30 and 40).…”

“…Electrophysiological recordings of photocurrents were made in two-electrode voltage-clamp mode from oocytes in Ringer's solution (pH 7.6) at a holding potential of −100 mV, and current-clamp mode from ventral longitudinal muscle 6 of Drosophila larvae (28). For associative olfactory learning, groups of ∼100 flies (4-7 d old) were trained as described by Tully and Quinn (39) with modifications.…”

cAMP Signals in Drosophila Motor Neurons Are Confined to Single Synaptic Boutons

“…To investigate this question in vivo, we used the neuromuscular junction (NMJ) of Drosophila melanogaster , which displays different forms of synaptic plasticity (Collins and DiAntonio, 2007, Frank, 2013, Koon et al., 2011, Ljaschenko et al., 2013), many of which are dependent on cAMP signaling (Griffith and Budnik, 2006, Olsen and Keshishian, 2012). Both structural and functional properties of larval neuromuscular synapses are heterogeneous, varying between boutons belonging to the same motor neuron (Paul et al., 2015, Peled and Isacoff, 2011).…”

Cell type-specific and time-dependent light exposure contribute to silencing in neurons expressing Channelrhodopsin-2

“…Although ChR2 expression, trafficking, and activation has been achieved in most types of nervous tissue (Li et al, 2005; Nagel et al, 2005; Bi et al, 2006; Schroll et al, 2006; Adamantidis et al, 2007; Zhang et al, 2007; Douglass et al, 2008; Mahoney et al, 2008; Baier and Scott, 2009; Guo et al, 2009; Han et al, 2009; Liu et al, 2009; Zhu et al, 2009; Gourine et al, 2010; Hagglund et al, 2010; Diester and et al, 2011; Figueiredo et al, 2011; Sasaki et al, 2012; Ljaschenko et al, 2013), little consideration has been given to the kinetics that constrain light-induced firing properties in different neuronal subtypes. Factors that affect the degree of neuronal photostimulation, including intrinsic differences in firing dynamics, membrane properties, and channel composition differ among neuronal cell types.…”