Cellular/Molecular
Persistent Na+ Current Enables Acetylcholine to Induce Spiking
Jason Yamada-Hanff and Bruce P. Bean
(see pages 15011–15021)
Acetylcholine modulates neuronal activity throughout the brain, and loss of cholinergic signaling contributes to cognitive decline in Alzheimer's disease. In the hippocampus, acetylcholine acts primarily on muscarinic receptors (mAChRs) and increases excitability of CA1 pyramidal neurons, often resulting in spontaneous spiking. Yamada-Hanff and Bean investigated the ionic basis of this effect in mouse hippocampal slices. Acetylcholine did not change the threshold for spike generation, but shifted the balance of inward and outward currents at all voltages. Unlike in control cells, where net current was outward at the resting membrane potential, net current was inward at all holding potentials below −40 mV in acetylcholine-treated neurons. As a result, the neurons depolarized to spike threshold from any subthreshold membrane potential and thus exhibited spontaneous spiking. Although spontaneous activity depended on the voltage-dependent activation of the persistent sodium current (INaP), acetylcholine did not affect this current. Instead, it likely activated a nonselective cation conductance that allowed slow depolarization to the INaP activation voltage.
Development/Plasticity/Repair
Death Receptor 6 Has a Role in Axonal Pruning in Adult Mice
Sally A. Marik, Olav Olsen, Marc Tessier-Lavigne, and Charles D. Gilbert
(see pages 14998–15003)
Loss of peripheral input to regions of primary sensory cortex causes sprouting and pruning of cortical axons in adjacent regions; this allows spared sensory inputs to make use of functionally deafferented cortex. After whiskers are plucked in adult mice, for example, regions of somatosensory barrel cortex that represent removed whiskers shrink, whereas barrels representing adjacent whiskers expand. Brain derived neurotrophic factor is thought to trigger axonal sprouting after deafferentation, and Marik et al. now provide evidence that death receptor 6 (DR6) is involved in axonal pruning. Although death receptors are thus named because they trigger apoptosis when activated by extracellular ligands, DR6 was previously found to regulate axonal pruning during development. Marik et al. show that this role persists in adults. Unlike wild-type animals, adult DR6-null mice exhibited almost no axonal pruning in barrel cortex after whiskers were removed. Even before whisker removal, more axons projected horizontally between barrels in DR6-null mice than in controls, suggesting developmental pruning was also deficient.
Reconstructions of axonal arbors in barrel cortex 1 d after whiskers were plucked. In wild-type mice (left), many axonal segments had been added (yellow) or pruned (red). Although axons were also added in DR6-null mice (right), few were pruned, and most were unchanged between imaging sessions (blue). See the article by Marik et al. for details.
Systems/Circuits
Mice Lacking MNTB Can Still Localize Sounds
Walid Jalabi, Cornelia Kopp-Scheinpflug, Paul D. Allen, Emanuele Schiavon, Rita R. DiGiacomo, et al.
(see pages 15044–15049)
Mammals localize sounds by comparing the amplitude and time of arrival of sounds at each ear. Interaural level differences (ILDs) are particularly important in small-headed mammals, in which interaural time disparities are small. ILDs are computed by neurons in the lateral superior olive (LSO), which integrate excitatory input from the ipsilateral ear with inhibitory input from the medial nucleus of the trapezoid body (MNTB), which receives inputs from the contralateral ear. Jalabi et al. were therefore surprised to find that knocking out the transcription factor En1, which prevented formation of the MNTB, had relatively minor effects on sound localization in mice. Although the ability to detect rapid shifts in sound location was impaired, spatial acuity did not differ significantly from controls. Moreover, although MNTB was previously thought to provide the main glycinergic inhibition to the LSO, the number of glycinergic terminals in LSO was reduced by only ∼30% in mutant mice, indicating LSO receives substantial glycinergic innervation from an unknown source.
Behavioral/Cognitive
Contrast Sensitivity Exhibits Circadian Oscillation
Christopher K. Hwang, Shyam S. Chaurasia, Chad R. Jackson, Guy C.-K. Chan, Daniel R. Storm, et al.
(see pages 14989–14997)
Contrast sensitivity, the ability to discriminate spatial variations in light intensity, is a critical component of visual processing in mammals. Dopamine, released by amacrine cells in the retina, increases contrast sensitivity by acting on D4 receptors (D4Rs). Dopamine synthesis and release and D4R expression are modulated by circadian clocks and Hwang et al. propose that contrast sensitivity also has a circadian rhythm in mice. The daytime peak in contrast sensitivity was significantly reduced in D4R-null mice, as was circadian oscillation in expression of the clock-regulating transcription factor neuronal PAS-domain protein 2 (NPAS2). NPAS2 was detected almost exclusively in a subset of retinal ganglion cells (RGCs), and it was required to drive circadian oscillation of adenylyl cyclase type 1 (AC1). Knocking out either of these proteins reduced the daily peak in contrast sensitivity. It should be noted, however, that because contrast sensitivity was tested using bands moving in a single direction, reduced ability to detect such movement might underlie the observed effects.
