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

Abstract

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.

• Authors: Catherine A Vickers, Benjamin Stephens, Julian Bowen, Gordon W Arbuthnott, Seth G N Grant, Cali A Ingham
• Journal: Brain research (Brain Res) Vol. 1090 Issue 1 Pg. 89-98 (May 23 2006) ISSN: 0006-8993 [Print] Netherlands
• PMID: 16677619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Disks Large Homolog 4 Protein
• Dlg4 protein, mouse
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• NR2B NMDA receptor
• Neuropeptides
• Receptors, N-Methyl-D-Aspartate
• Dlgh3 protein, mouse
• Guanylate Kinases

Topics

• Animals
• Cell Differentiation (genetics)
• Corpus Striatum (abnormalities, cytology, metabolism)
• Dendritic Spines (metabolism, pathology, ultrastructure)
• Disks Large Homolog 4 Protein
• Guanylate Kinases
• Hippocampus (abnormalities, cytology, metabolism)
• Intracellular Signaling Peptides and Proteins (genetics)
• Membrane Proteins (genetics)
• Mice
• Mice, Knockout
• Neuronal Plasticity (genetics)
• Neuropeptides (metabolism)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Synaptic Membranes (genetics, metabolism, ultrastructure)
• Synaptic Transmission (genetics)