Decrease of a Current Mediated by Kv1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism.

The mechanism underlying a hypercholinergic state in Parkinson's disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.

Hedgehog Signaling Regulates the Ciliary Transport of Odorant Receptors in Drosophila.

Hedgehog (Hh) signaling is a key regulatory pathway during development and also has a functional role in mature neurons. Here, we show that Hh signaling regulates the odor response in adult Drosophila olfactory sensory neurons (OSNs). We demonstrate that this is achieved by regulating odorant receptor (OR) transport to and within the primary cilium in OSN neurons. Regulation relies on ciliary localization of the Hh signal transducer Smoothened (Smo). We further demonstrate that the Hh- and Smo-dependent regulation of the kinesin-like protein Cos2 acts in parallel to the intraflagellar transport system (IFT) to localize ORs within the cilium compartment. These findings expand our knowledge of Hh signaling to encompass chemosensory modulation and receptor trafficking.

Did Emperor Moctezuma II's head injury and subsequent death hasten the fall of the Aztec nation?

This article analyzes the head injury of Emperor Moctezuma as one of those injuries that affected the course of history. The Emperor's death arguably changed the fate of an entire nation and led to the destruction of the Aztec civilization. Moctezuma died in the evening hours of June 30, 1520, in his palace in the Aztec capital, Tenochtitlan, while a prisoner of the Spanish conquistadors. The Emperor had been speaking to his people in an effort to persuade them to cease hostilities against Hernán Cortés, his Spanish soldiers, and Indian allies. Both Spanish and Indian contemporary sources document that he sustained a severe head injury when one of his own warriors hit him with a rock thrown from a sling. However, after the Conquest of Mexico some of the information collected by Spanish friars from Indian stories, songs, and pictorial representations raised the possibility that Moctezuma died of strangulation or stabbing at the hands of the Spaniards. There is even a suggestion of suicide. This issue remains unresolved and emotionally charged. The historical and clinical analysis of the events surrounding Moctezuma's death indicates that the Emperor most likely died as a consequence of head injury. The author has attempted to present a neutral analysis but agrees with Benjamin Keen that neutrality may be unattainable, no matter how remote the subject of historical inquiry is from the present.

The Edwin Smith papyrus: a clinical reappraisal of the oldest known document on spinal injuries.

Dating from the seventeenth century B.C: . the Edwin Smith papyrus is a unique treatise containing the oldest known descriptions of signs and symptoms of injuries of the spinal column and spinal cord. Based on a recent "medically based translation" of the Smith papyrus, its enclosed treasures in diagnostic, prognostic and therapeutic reasoning are revisited. Although patient demographics, diagnostic techniques and therapeutic options considerably changed over time, the documented rationale on spinal injuries can still be regarded as the state-of-the-art reasoning for modern clinical practice.