Cellular/Molecular
CNG-Modulin Mediates Ca2+-Dependent cGMP Sensitivity in Cones
Tatiana I. Rebrik, Inna Botchkina, Vadim Y. Arshavsky, Cheryl M. Craft, and Juan I. Korenbrot
(see pages 3142–3153)
In photoreceptors, cyclic nucleotide-gated (CNG) channels activated by cGMP are open in the dark, allowing influx of calcium, which is continuously extruded. Upon light absorption, cGMP is hydrolyzed and CNG channels close, attenuating calcium influx. If illumination continues, intracellular Ca2+ levels fall. In cones, the cGMP sensitivity of CNG channels increases as Ca2+ levels decrease, increasing the probability of channel opening. This helps terminate the phototransduction signal and underlies the adaptation that extends cones' dynamic range. Calcium does not modulate CNG channels directly, however; instead, it binds to a soluble protein that modulates the channels. Until now, the identity of this protein was unknown. Rebrik et al. found the protein, which they name CNG-modulin, by screening a fish retinal cDNA library for proteins that bind Ca2+ and CNG channels. CNG-modulin is expressed in cones, but not rods, and recombinant CNG-modulin restored normal Ca2+-dependent ligand sensitivity of CNG channels in cone membrane patches.
Development/Plasticity/Repair
Serotonin 5-HT7 Receptors Regulate Postnatal Synaptogenesis
Fritz Kobe, Daria Guseva, Thomas P. Jensen, Alexander Wirth, Ute Renner, et al.
(see pages 2915–2930)
Serotonin acts on more than 14 receptor types throughout the CNS, regulating a broad range of functions, from locomotion to cognition. Serotonin also affects the development of neural circuits underlying these functions by regulating migration, neurite outgrowth, and synaptogenesis. One receptor mediating such effects is 5-HT7, which couples to the G-protein Gα12. Gα12 activates the small GTPase Cdc42, which regulates actin dynamics. Kobe et al. report that, in addition to its previously described role in neurite outgrowth, the 5-HT7/Gα12 signaling pathway stimulates synapse formation. A 5-HT7 agonist increased the number of dendritic protrusions, AMPA receptor and synaptophysin puncta, and frequency of EPSPs and spikes in cultured mouse hippocampal neurons. These effects were absent in neurons lacking either 5-HT7 receptors or Gα12. The expression of 5-HT7 and Gα12 and the effects of 5-HT7 agonist declined as neurons aged, suggesting the primary role of 5-HT7 in hippocampus is in establishing neural circuits.
Behavioral/Systems/Cognitive
Some Auditory Cortical Neurons Might Signal Stimulus Onset
Romain Brasselet, Stefano Panzeri, Nikos K. Logothetis, and Christoph Kayser
(see pages 2998–3008)
Sensory stimuli are represented by changes in neuronal spike rate that can be precise on millisecond time scales. In auditory cortical neurons, rapid frequency modulation carries much information about stimuli; but to fully exploit this information, animals must have an internal temporal reference to align spike trains to. Proposed references include efferent copies of motor commands, the phase of ongoing cortical oscillations, and aggregate population responses. The last is most likely used by auditory neurons, and Brasselet et al. identified a population of macaque auditory cortical neurons that were well suited for this role. Unlike most auditory neurons, which responded with variable latency to specific auditory stimuli, these neurons responded with short, constant latency and high frequency to every auditory stimulus. Aligning the spike trains of variable-latency neurons to the onset of spiking in fixed-latency neurons preserved much of the information present when the trains were aligned to actual stimulus onset.
Trial-averaged temporal response pattern (bright colors represent high response amplitude) to 12 stimuli (vertical axis) of two auditory cortex neurons, one that responds similarly to every stimulus (top), and one that responds variably to stimuli (bottom). See the article by Brasselet et al. for details.
Neurobiology of Disease
Neuregulin-1 Regulates LTP via ErbB4
Alon Shamir, Oh-Bin Kwon, Irina Karavanova, Detlef Vullhorst, Elias Leiva-Salcedo, et al.
(see pages 2988–2997)
Mutations in genes encoding neuregulin-1 and its receptor, ErbB4, have been linked to schizophrenia, but how the affected proteins contribute to disease pathology is unknown. ErbB4 is expressed primarily in inhibitory interneurons, particularly those that express parvalbumin (PV), and neuregulin regulates synaptic plasticity and GABAergic transmission. Shamir et al. show that, besides reversing LTP induced by theta-burst stimulation (TBS) in mouse hippocampal slices, addition of recombinant neuregulin-1 prevented LTP induction. In contrast, knocking out ErbB4 selectively in PV-expressing interneurons enhanced TBS-induced LTP and prevented LTP reversal. Although mouse behaviors thought to model schizophrenia—reduced prepulse inhibition of startle responses, hyperactivity, and impaired working memory—were produced by knocking out ErbB4 in PV-expressing neurons, more widespread ErbB4 deletion produced additional effects, namely, reduced anxiety-like and fear behaviors. These effects must therefore be mediated by interneurons that do not express PV. Indeed, ErbB4-positive, PV-negative neurons are common in the amygdala, which is important in fear responses.
