Abstract
The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory proteins. JNK1 also phosphorylates dendritic spine proteins, and Jnk1-/- mice display a long-term depression deficit. Whether JNK1 or other JNKs regulate spine morphology is thus of interest. Here, we characterize dendritic spine morphology in hippocampus of mice lacking Jnk1-/- using Lucifer yellow labelling. We find that mushroom spines decrease and thin spines increase in apical dendrites of CA3 pyramidal neurons with no spine changes in basal dendrites or in CA1. Consistent with this spine deficit, Jnk1-/- mice display impaired acquisition learning in the Morris water maze. In hippocampal cultures, we show that cytosolic but not nuclear JNK, regulates spine morphology and expression of phosphomimicry variants of JNK substrates doublecortin (DCX) or myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1), rescue mushroom, thin, and stubby spines differentially. These data suggest that physiologically active JNK controls the equilibrium between mushroom, thin, and stubby spines via phosphorylation of distinct substrates.
Highlights
The hippocampus is the most extensively studied structure with regards to memory and learning.Changes in dendritic spine density and shape in the hippocampus correlate with spatial and associative learning in rodents [1,2,3,4]
To test if spatial learning and memory was affected in Jnk1-/- mice, animals were subjected to the Morris water maze (MWM) test [43]
During the reversal phase, when mice relearned a new place for the hidden platform, there was no genotypic difference (Figure 1a,b), and Jnk1-/- and wild-type mice both spent most of the time swimming in the “new target” quadrant during the reversal probe trial (Figure 1d)
Summary
The hippocampus is the most extensively studied structure with regards to memory and learning. Increased spine density improves synaptic efficacy [5] and increased spine head size correlates with synaptic strength [6,7,8] Such strengthening of synaptic currents, achieved through growth and stabilization of synapses, is known as long-term potentiation (LTP). Weakening of synaptic currents on the other hand, achieved through spine shrinkage, is known as long-term depression (LTD) Both forms of synaptic plasticity contribute to information storage and spatial memory formation in the hippocampus [9,10,11,12]. This study showed that JNK controls actin dynamics in thin spine heads These studies suggest that JNK isoforms regulate structural and neurophysiological aspects of synaptic plasticity. We examined the role of JNK1 targets DCX and MARCKSL1 in determining spine structure
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