Isolation of a Nonhistaminergic Pruritic Compound
Vemuri B. Reddy, Aurel O. Iuga, Steve G. Shimada, Robert H. LaMotte, and Ethan A. Lerner
(see pages 4331–4335)
Investigations of the neural mechanisms of itch have primarily focused on histamine pathways, but chronic itch can be resistant to antihistamines, suggesting that they involve another itch pathway. Because small hairs (spicules) that cover seedpods from the tropical legume cowhage (Mucuna pruriens) also provoke nonhistaminergic itching and stinging, the pruritic agent present in cowhage could prove useful for elucidating histamine-independent itch pathways. Reddy et al. have isolated and characterized this substance, which they call mucunain, from cowhage spicules. Mucunain was shown to be a cysteine protease, and inactivated spicules that were reconstituted with isolated or recombinant mucunain evoked itching, stinging, and burning sensations in human subjects, suggesting that mucunain is the sole pruritic compound in cowhage. The authors began unraveling the mucunainergic itch pathway by expressing the four known human protease-activated receptors (PARs) in HeLa cells. Mucunain activated PAR2 and PAR4.
Discrete Forms of Homeostatic Regulation in V1
Arianna Maffei and Gina G. Turrigiano
(see pages 4377–4384)
Homeostatic plasticity, which keeps neuronal spiking within an optimal range, can be achieved by several mechanisms, including synaptic and extrasynaptic changes. This week, Maffei and Turrigiano report that homeostatic plasticity in layer 2/3 visual cortical neurons in mice can take different forms, depending on how visual input is reduced. Both injection of TTX into the eye (which eliminates visual inputs) and lid suture (which reduces and decorrelates visual inputs) caused an increase in spontaneous firing in V1, indicative of homeostatic regulation. But whereas TTX injection increased excitatory drive and decreased inhibitory drive, lid suture reduced excitation without affecting inhibition. Instead, lid suture lowered the threshold voltage for spiking and increased the spike rate elicited by a given current injection. These changes in intrinsic excitability, possibly effected by modulation of voltage-dependent currents, were not seen following TTX injection, indicating that the same homeostatic increase in excitability can be produced by distinct mechanisms.
Face/Voice Integration in Macaques
Asif A. Ghazanfar, Chandramouli Chandrasekaran, and Nikos K. Logothetis
(see pages 4457–4469)
Like humans, monkeys match voices to faces, integrating auditory and visual information while communicating. To investigate multisensory integration in macaques, Ghazanfar et al. recorded simultaneously from the superior temporal sulcus (STS), an association area, and auditory cortex while monkeys viewed and/or heard recordings of their colony mates making coos and grunts. The authors found that activity in these two regions became more strongly correlated, and their phase relationships became less variable, when monkeys received both visual and auditory information compared to when they received either stimulus alone. Single-unit recordings revealed that ∼80% of neurons in auditory cortex that responded to vocalizations were multisensory: simultaneous visual stimuli enhanced the activity of some neurons and suppressed the activity of others. Interestingly, some of the neurons that responded to both coos and grunts in the auditory-only condition responded to a single coo or grunt in the multisensory condition: that is, addition of visual information increased the neurons' selectivity.
Neurobiology of Disease
Developmental Role of MicroRNAs in Forebrain
Tigwa H. Davis, Trinna L. Cuellar, Selina M. Koch, Alison J. Barker, Brian Harfe, Michael T. McManus, and Erik M. Ullian
(see pages 4322–4330)
MicroRNAs (miRNAs) are short noncoding RNAs that base pair with specific mRNAs to trigger posttranslational gene silencing. Dicer processes pre-miRNAs into mature miRNAs and facilitates their incorporation into the RNA-induced silencing complex. Although hundreds of miRNAs have been identified in humans, their role in the nervous system is largely unexplored. Davis et al. used a forebrain-specific conditional knock-out of Dicer to investigate the role of miRNAs in these brain regions. Expression of mutant Dicer in excitatory neurons of the cortex, hippocampus, and caudate putamen resulted in progressive loss of miRNA. Mutant mice were ataxic, tremulous, and short-lived, and their brains were ∼50% smaller than normal, probably due partly to a 5.5-fold increase in apoptosis. Dendritic branching was reduced, spine length was increased, and axonal pathfinding was disrupted. These results are consistent with those of other experiments that suggest miRNAs play roles in neuronal development and protection from apoptosis.