Neurone specific regulation of dendritic spines in vivo by post synaptic density 95 protein (PSD-95)

• Published in: Brain research 2006-05, Vol.1090 (1), p.89-98
• Main Authors: Vickers, Catherine A., Stephens, Benjamin, Bowen, Julian, Arbuthnott, Gordon W., Grant, Seth G.N., Ingham, Cali A.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Cell Differentiation - genetics; Central nervous system; Corpus Striatum - abnormalities; Corpus Striatum - cytology; Corpus Striatum - metabolism; Dendritic Spines - metabolism; Dendritic Spines - pathology; Dendritic Spines - ultrastructure; Disks Large Homolog 4 Protein; Fundamental and applied biological sciences. Psychology; Guanylate Kinases; Hippocampus - abnormalities; Hippocampus - cytology; Hippocampus - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Membrane Proteins - genetics; Mice; Mice, Knockout; Mouse; Neuronal Plasticity - genetics; Neuropeptides - metabolism; NMDA receptor; Plasticity; Receptors, N-Methyl-D-Aspartate - metabolism; Synapse; Synaptic Membranes - genetics; Synaptic Membranes - metabolism; Synaptic Membranes - ultrastructure; Synaptic Transmission - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.03.075

Post synaptic density protein 95 (PSD-95) is a postsynaptic adaptor protein coupling the NMDA receptor to downstream signalling pathways underlying plasticity. Mice carrying a targeted gene mutation of PSD-95 show altered behavioural plasticity including spatial learning, neuropathic pain, orientation preference in visual cortical cells, and cocaine sensitisation. These behavioural effects are accompanied by changes in long-term potentiation of synaptic transmission. In vitro studies of PSD-95 signalling indicate that it may play a role in regulating dendritic spine structure. Here, we show that PSD-95 mutant mice have alterations in dendritic spine density in the striatum (a 15% decrease along the dendritic length) and in the hippocampus (a localised 40% increase) without changes in dendritic branch patterns or gross neuronal architecture. These changes in spine density were accompanied by altered expression of proteins known to interact with PSD-95, including NR2B and SAP102, suggesting that PSD-95 plays a role in regulating the expression and activation of proteins found within the NMDA receptor complex. Thus, PSD-95 is an important regulator of neuronal structure as well as plasticity in vivo.