The Polysialylated Form of the Neural Cell Adhesion Molecule (PSA-NCAM) Is Expressed in a Subpopulation of Mature Cortical Interneurons Characterized by Reduced Structural Features and Connectivity

Abstract

Principal neurons in the adult cerebral cortex undergo synaptic, dendritic, and spine remodeling in response to different stimuli, and several reports have demonstrated that the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) participates in these plastic processes. However, there is only limited information on the expression of this molecule on interneurons and on its role in the structural plasticity of these cells. We have found that PSA-NCAM is expressed in mature interneurons widely distributed in all the extension of the cerebral cortex and have excluded the expression of this molecule in most principal cells. Although PSA-NCAM expression is generally considered a marker of immature neurons, birth-dating analyses reveal that these interneurons do not have an adult or perinatal origin and that they are generated during embryonic development. PSA-NCAM expressing interneurons show reduced density of perisomatic and peridendritic puncta expressing different synaptic markers and receive less perisomatic synapses, when compared with interneurons lacking this molecule. Moreover, they have reduced dendritic arborization and spine density. These data indicate that PSA-NCAM expression is important for the connectivity of interneurons in the adult cerebral cortex and that its regulation may play an important role in the structural plasticity of inhibitory networks.

RETRACTED: Identification of gene ontologies linked to prefrontal–hippocampal functional coupling in the human brain

“…NRCAM-PSA-expressing interneurons in mice show reduced dendritic spine numbers, decreased arborization, and changes in the synaptic connectivity (54). A study of cultured hippocampal neurons showed that PSA-NRCAM is required for N-methyl-D-aspartate (NMDA) receptor-dependent LTP and acts as an antagonist at N2RB-subunit-bearing NMDA receptors, preventing glutamate-induced cell death (55,56).…”

The Neural Cell Adhesion Molecule (NCAM) Promotes Clustering and Activation of EphA3 Receptors in GABAergic Interneurons to Induce Ras Homolog Gene Family, Member A (RhoA)/Rho-associated protein kinase (ROCK)-mediated Growth Cone Collapse

“…The NCAM extracellular region can be modified by polysialylation (PSA-NCAM), which is implicated in mediating synaptic plasticity (33). PSA-NCAM is highly expressed in the embryonic and early postnatal stages and in interneuron populations in the mature cortex (33)(34)(35)(36). The 140-kDa isoform NCAM140 interacts physically and functionally with EphA3 to a greater extent than other isoforms (2) and is most prominent in axonal growth cones of developing neuronal cells (37).…”

Streptozotocin diabetic mice display depressive-like behavior and alterations in the structure, neurotransmission and plasticity of medial prefrontal cortex interneurons

“…Interestingly, interneurons, as pyramidal neurons, in the mPFC also respond with structural changes to chronic stress, increasing their dendritic arborization (Gilabert-Juan et al, 2013). These changes in interneuronal structure may be mediated by the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which is exclusively expressed by interneurons in the mPFC of rodents (Gómez-Climent et al, 2011;Varea et al, 2005) and humans (Varea et al, 2007b). The expression of PSA-NCAM is regulated by chronic stress in the hippocampus (Pham et al, 2003;Sandi et al, 2001), the amygdala (Cordero et al, 2005), the piriform cortex (Nacher et al, 2004) and other cerebral regions (see (Sandi, 2004), for review).…”