Excitatory amino acid involvement in dendritic spine formation, maintenance and remodelling

Abstract

In the central nervous system, most excitatory synapses occur on dendritic spines, which are small protrusions from the dendritic tree. In the mature cortex and hippocampus, dendritic spines are heterogeneous in shape. It has been shown that the shapes of the spine can affect synapse stability and synaptic function. Dendritic spines are highly motile structures that can undergo actin-dependent shape changes, which occur over a time scale ranging from seconds to tens of minutes or even days. The formation, remodelling and elimination of excitatory synapses on dendritic spines represent ways of refining the microcircuitry in the brain. Here I review the current knowledge on the effects of modulation of AMPA and NMDA ionotropic glutamate receptors on dendritic spine formation, motility and remodelling.

R. Anne McKinney (McGill University, Montreal, Canada) received her BSc (Hons) in Biomedical Sciences and her DPhil in Neuroscience from the University of Ulster, Coleraine, Northern Ireland, in 1992. She completed her postdoctoral fellowship and had her first independent research group in the Department of Neurophysiology, Brain Research Institute, University of Zurich, Switzerland. She is currently an Associate Professor in the Department of Pharmacology and Therapeutics, McGill University. Her principle research interest is the mechanisms involved in development, maintenance and plasticity of excitatory synapses in the CNS, during physiological and pathological conditions such as epilepsy and autism. She has won many awards for her work including in 1999 the Pfizer Research Prize in Basic Neuroscience and in 2009 the Hugh and Helene McPherson Memorial Award.

Figure 1. Diversity of spine shape

A, three-dimensional tertiary portion of the dendritic tree of a CA1 pyramidal cell from a green fluorescent protein-expressing mouse brain. Dendritic spines are classified into three main types: short, stubby spines (<0.5 μm in length) (B), mushroom-type spines, consisting of a short neck and mushroom-shaped head (C), or thin, long spines with an elongated neck and small head (D). Scale bar, 1 μm.

Figure 2. Chronic blockade of AMPA receptors on mature dendritic spines results in synapse loss and an increase in excitatory shaft synapses

Illustration of 3D reconstruction from serial electron microscopy from control (left) and sister cultures chronically treated with an antagonist for AMPA receptors (right) (modified from Mateos et al. 2007). Scale bar, 0.5 μm.

Figure 3. Inverse correlation between spine motility and membrane trafficking

The more motile the dendritic spine the slower the diffusion co-efficient of membrane bound GFP after FRAP analysis (modified from Richards et al. 2004).