Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitut...

OBJECTIVE Decreased density of dendritic spines in adult schizophrenia subjects has been hypothesized to result from increased pruning of excess synapses in adolescence. In vivo imaging studies have confirmed that synaptic pruning is largely driven by the loss of large or mature synapses. Thus, increased pruning throughout adolescence would likely result in a deficit of large spines in adulthoo...

Editor's Note: These short, critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and commentary. For more information on the format and purpose of the Journal Club, please see The postsynaptic components of excita-tory synapses are located a...

Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a key role in N-methyl-D-aspartate (NMDA) receptor-dependent long-term synaptic plasticity; its location is critical for signal transduction, and may provide clues that further elucidate its function. We therefore examined the subcellular localization of CaMKII in CA1 stratum radiatum of adult rat hippocampus, by using immuno-electro...

The number and shape of dendritic spines are influenced by activity and regulated by molecules that organize the actin cytoskeleton of spines. Cortactin is an F-actin binding protein and activator of the Arp2/3 actin nucleation machinery that also interacts with the postsynaptic density (PSD) protein Shank. Cortactin is concentrated in dendritic spines of cultured hippocampal neurons, and the N...

We studied the lysophosphatidic acid receptor-1 (LPA1) gene, which we found to be expressed endogenously in cultured hippocampal neurons, and in vivo in young (1-week-old) rat brain slices. Overexpressed green fluorescent protein (GFP)-tagged, membrane-associated LPA1 accumulated in a punctate manner over the entire dendritic tree and caused an increase in dendritic spine density. About half of...

Mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) are implicated in neuropsychiatric disorders including autism. Previous studies report that PTEN knockdown in neurons in vivo leads to increased spine density and synaptic activity. To better characterize synaptic changes in neurons lacking PTEN, we examined the effects of shRNA knockdown of PTEN in basolateral amygdala...

Alzheimer's disease is thought to be caused by β-amyloid peptide (Aβ)-dependent synaptic dysfunction. However, the signaling pathways connecting Aβ and synaptic dysfunction remain elusive. Here we report that Aβ transiently increases the expression level of centaurin-α1 (CentA1) in neurons, which induces a Ras-dependent association of Elk-1 with mitochondria, leading to mitochondrial and synapt...

1. Neuroscientists are currently hypothesizing on how voltage-dependent channels, in dendrites with spines, may be spatially distributed or how their numbers may divide between spine heads and the dendritic base. A new cable theory is formulated to investigate electrical interactions between many excitable and/or passive dendritic spines. The theory involves a continuum formulation in which the...

The damage of dopaminergic neurons that innervate the striatum has been considered to be the proximate cause of Parkinson's disease (PD). In the dopamine-denervated state, the loss of dendritic spines and the decrease of dendritic length may prevent medium spiny neuron (MSN) from receiving too much excitatory stimuli from the cortex, thereby reducing the symptom of Parkinson's disease. However,...