Polysialic acid and activity-dependent synapse remodeling

Abstract

Polysialic acid (PSA) is a large carbohydrate added post-translationally to the extracellular domain of the Neural Cell Adhesion Molecule (NCAM) that influences its adhesive and other functional properties. PSA-NCAM is widely distributed in the developing nervous system where it promotes dynamic cell interactions, like those responsible for axonal growth, terminal sprouting and target innervation. Its expression becomes restricted in the adult nervous system where it is thought to contribute to various forms of neuronal and glial plasticity. We here review evidence, obtained mainly from hypothalamic neuroendocrine centers and the olfactory system, that it intervenes in structural synaptic plasticity and accompanying neuronal-glial transformations, making possible the formation and elimination of synapses that occur under particular physiological conditions. While the mechanism of action of this complex sugar is unknown, it is now clear that it is a necessary molecular component of various cell transformations, including those responsible for activity-dependent synaptic remodeling.

Figure 1

Highly sialylated Neural Cell Adhesion Molecule (PSA-NCAM) in adult brain cell populations involved in different types of synaptic plasticity. Top: diagrammatic representation of sagittal (A) and coronal (B) views of the rat brain showing areas containing cells enriched in PSA-NCAM. In grey, neurogenic sites. H, hippocampus; OB, olfactory bulb; OM, olfactory mucosa; PC, piriform cortex; SON, supraoptic nucleus; SVZ, subventricular zone. Bottom: Immunoreactions for polysialic acid (PSA) reveal highly immunopositive neurons (C, D and F) in restricted areas known to undergo plasticity, like the olfactory bulb (C), hippocampus (D) and the piriform cortex (F). In neuroendocrine centers like the SON (E), a strong reaction fills the neuropile and is due to immunoreaction on neuronal and glial (astrocytic) processes. Note that newly generated (top, green nuclei) and non-newly generated cells (top, unstained nuclei) display a typical punctate reaction on their cell membrane (see also C and D). DCX, doublecortin.