Cellular/Molecular
Regulation of SK Channels by Adrenaline
E. S. Louise Faber, Andrew J. Delaney, John M. Power, Petra L. Sedlak, James W. Crane, and Pankaj Sah
(see pages 10803–10813)
Emotional events are thought to be well remembered in part because stress-induced elevation of adrenaline activates β-adrenergic receptors in the basolateral amygdala, enhancing memory formation. This week, Faber et al. show that β-adrenergic agonists increase EPSP amplitude and enhance long-term potentiation (LTP) at cortico-amygdala synapses in slices. Using various activators and inhibitors, the authors investigated the molecular processes mediating this effect, and they report that it involves regulation of postsynaptic membrane expression of small-conductance calcium-activated potassium (SK) channels. SK channels are activated by calcium influx through NMDA receptors, and they act as a shunt that reduces EPSP amplitude. Like other membrane proteins, SK channels are endocytosed and recycled back to the membrane. Activation of β-adrenergic receptors activates adenylate cyclase, leading to cAMP production and activation of cAMP-dependent protein kinase (PKA). PKA phosphorylates SK channels, which blocks resinsertion of SK channels after endocytosis. This reduces the shunt, thus increasing EPSP amplitude and enhancing LTP.
Development/Plasticity/Repair
Role of Notch1 in Plasticity
Martijn Dahlhaus, Josephine M. Hermans, Leonard H. Van Woerden, M. Hadi Saiepour, Kazu Nakazawa, Huibert D. Mansvelder, J. Alexander Heimel, and Christiaan N. Levelt
(see pages 10794–10802)
Experience-dependent plasticity is exemplified by shifts in ocular dominance produced by monocular deprivation during the critical period of development. This plasticity depends on structural changes, including growth and loss of neurites and dendritic spines. One might expect, therefore, that molecules that regulate morphological development are also important in experience-dependent plasticity. One such molecule is the transmembrane protein Notch1, whose activation during development leads to increased dendritic branching and reduced extension. Dahlhaus et al. expressed constitutively active Notch1 specifically in pyramidal neurons during the visual critical period of mice. Notch1 activity decreased the number of dendritic spines and filopodia in visual cortex and reduced the induction of long-term potentiation between layer 4 and layer 2/3. Surprisingly, these changes did not obviously alter the ocular dominance shift produced by monocular deprivation. Instead, the functional consequence of reduced anatomical plasticity and LTP was a larger reduction in visual acuity following deprivation.
Expression of a constitutively active form of Notch1 (bottom) reduces the number of spines and filopodia on cortical pyramidal cell dendrites compared to control (top). See the article by Dahlhaus et al. for details.
Behavioral/Systems/Cognitive
Reorganization of Somatosensory Cortex after Deafferentation
Neeraj Jain, Hui-Xin Qi, Christine E. Collins, and Jon H. Kaas
(see pages 11042–11060)
When sensory cortex is deprived of inputs, functional reorganization occurs and different sensory inputs begin to drive the deafferented area. Several studies have shown orderly changes over a few millimeters—for example, in the barrel cortex after single whisker ablation. Jain et al. show that reorganization can be far more extensive than previously appreciated. Two years after sensory inputs from some fingers were removed by severing the dorsal column in macaques, some neurons in the deafferented primary somatosensory cortex responded to inputs from the remaining fingers as expected; but other neurons responded only to stimulation of the chin, and many responded to both chin and hand stimulation. The range of the reorganization was striking: in one monkey, the cortical area responsive to chin stimulation reached into the area previously devoted to foot, 2 cm from the original representation. This cortical reorganization likely depended on similar reorganization that occurred in the thalamus.
Neurobiology of Disease
Cell Cycle Re-Entry in Alzheimer's Disease
Nicholas H. Varvel, Kiran Bhaskar, Anita R. Patil, Sanjay W. Pimplikar, Karl Herrup, and Bruce T. Lamb
(see pages 10786–10793)
Amyloid plaques are the defining characteristic of Alzheimer's disease (AD), but several studies suggest that soluble amyloid protein is more damaging to neurons. In fact, many signs of neurodegeneration occur before amyloid plaques appear. One such sign is neuronal re-entry into the cell cycle, which occurs in several neurodegenerative diseases. In humans with mild cognitive impairment, DNA replication and expression of cell cycle proteins (e.g., cyclins) appear in brain regions that undergo neurodegeneration in AD. Using transgenic mouse models of AD, Varvel et al. found that cyclins were expressed in frontal cortex many months before plaques appeared, and they were expressed even in mice that never develop plaques. Cyclin expression was prevented by blocking the abnormal processing of amyloid precursor protein that produces amyloid β. Furthermore, amyloid oligomers triggered DNA replication and cyclin expression in primary cortical neurons in vitro, indicating that this early characteristic of degeneration is triggered by soluble amyloid.
