The dynamics of excitatory synapse formation on dendritic spines

Abstract

Dendritic spines, the postsynaptic compartments of most functional excitatory synapses in the Central Nervous System (CNS), are highly dynamic structures, having the ability to grow, change shape, or retract in response to varying levels of neuronal activity. This dynamic nature of spines allows modifications in brain circuitry and connectivity, thus participating in fundamental processes such as learning, recall, and emotional behaviors. Although many studies have characterized the precise molecular identities and signaling pathways by which spines initially form, little is known about the actual time course over which they mature into functional postsynaptic compartments of excitatory synapses. A recent publication in Neuron addresses this issue by studying dendritic spine growth in response to multiphoton glutamate uncaging, simultaneously monitoring the amplitudes of the resultant postsynaptic currents and intracellular Ca(2+) transients within individual spines in CA1 pyramidal neurons in organotypic cultures of postnatal hippocampal slices. The authors describe that dendritic spines are able to respond to glutamate shortly after their formation, leading to the conclusion that spine growth and glutamate receptor recruitment are closely coupled temporally. AMPA receptor-mediated currents exhibited similar amplitudes in newly formed spines compared with older, more mature spines when their volume was taken into account. In addition, NMDA receptor-mediated currents also appeared early after spine formation, although the amount of Ca(2+) entry through these receptors was significantly lower in newly formed spines compared to older, mature spines. Within just a couple of hours, these newly formed spines were contacted by presynaptic terminals, thus acquiring a morphological appearance indistinguishable from already existing mature excitatory synapses.

Figure 1. The structure of dendritic spines of hippocampal pyramidal neurons

Using particle-mediated gene transfer (a.k.a. gene gun), organotypic slice cultures were transfected with cDNA coding for eYFP. Top panels: Laser-scanning confocal microscopy images of a pyramidal neuron in area CA1 are shown at different magnifications to illustrate the complexity of their dendritic arbor and the abundance of dendritic spines in secondary and tertiary branches. Bottom left panel: A maximum-intensity projection of z-stacks shows a dendritic segment studded with the most common spine morphologies, i.e. stubby, mushroom and thin. The cartoon illustrates the geometrical dimensions measured in individual spines to categorize them. Bottom right panel: A mushroom dendritic spine (outlined in green) forms an asymmetric synapse with a single presynaptic terminal (outlined in red) in stratum radiatum of area CA1 in organotypic slice culture. We thank Dr. Christopher Chapleau for these images.