1. Mapping Ethanol Sensitivity and Tolerance in the Fly
Nancy L. Urizar, Zhiyong Yang, Howard J. Edenberg, and Ronald L. Davis
Invertebrates and humans display some common behavioral responses to ethanol, including reduced responsiveness and rapid behavioral tolerance. This week, Urizar et al. traced these effects in Drosophila to expression of the signaling protein Homer. Approximately 70% of wild-type flies were “sedated” (i.e. were motionless or had fallen on their back/side) after first exposure to ethanol vapor, whereas only 10% were sedated after a second exposure, consistent with rapid tolerance. Of 600 genes that changed in response to alcohol exposure, the authors focused on homer, whose mRNA decreased after single or repeated ethanol exposures. Mutant male flies lacking homer were more sedated by a single ethanol exposure, and had reduced tolerance. These effects were rescued by transgenic pan-neuronal expression of Homer or when Homer expression was driven in the ellipsoid body, part of the central complex thought to be involved in control of locomotor activity.
2. Experience-Dependent Gustatory Development
Jamie E. Mangold and David L. Hill
This week, Mangold and Hill provide evidence that gustatory deprivation, in this case sodium restriction, alters sensory nerve endings in the brainstem. The authors fed pregnant rats a reduced-sodium diet between embryonic day 3 (E3) and E12 of fetal development, a period preceding tongue formation. Other pregnant rats received the custom diet from E3 to postnatal day 28 (P28). The authors labeled three gustatory nerves to visualize their central terminal fields in the nucleus of the solitary tract. At 40 d postnatal, rats born to mothers fed the low-sodium diet from E3 to E12 had an enlargement of all three terminal fields. Although the terminal fields were expanded in rats fed the custom diet until P28, they were only half the size of the E3–E12 group. Thus, these effects appear to be dependent on experience, but not neural activity per se, because the exposure preceded development of the tongue.
3. Painful Memories
Marie-Claire Albanese, Emma G. Duerden, Pierre Rainville, and Gary H. Duncan
The memory of pain has affective components, as well as components devoted to nitty-gritty details such as location and intensity. Albanese et al. compared functional magnetic resonance images of human subjects in a delayed-discrimination task that engaged short-term memory of pain location and intensity. Subjects were cued to the trial (memory or control), after which a heat stimulus was delivered to one hand location, then 6–10 s later to a second hand location. In the memory trial, the subjects indicated which stimulus was stronger. As expected, stimuli elevated blood oxygen level-dependent responses in primary somatosensory cortex/posterior parietal cortex (SI/PPC), secondary somatosensory cortex (SII), and anterior insular cortex (aIC). Memory trials, however, evoked activity in SI/ PPC and aIC but not in SII. The anterior cingulate cortex, associated with affective aspects of pain, was not activated in the memory trial, suggesting that an affective component was not required to discriminate the sensory features of painful stimuli.
4. The Neurodevelopmental Defects of the Arx-Deficient Mouse
Elena Colombo, Patrick Collombat, Gaia Colasante, Marta Bianchi, Jason Long, Ahmed Mansouri, John L. R. Rubenstein, and Vania Broccoli
Mutations of the human ARX gene, a transcription factor that maps to the X chromosome, cause a range of neurological manifestations, including mental retardation, seizures, movement disorders, and abnormal cortical development. In this week’s Journal, Colombo et al. used mutant mice to examine the impact of Arx loss-of-function mutations on basal ganglia structures. Arx is expressed in progenitor cells and neurons of the lateral and medial ganglionic eminence (LGE and MGE), which give rise to the striatum and pallidum, nucleus basalis as well as cortical interneurons. Arx-deficient mice die soon after birth; thus, the authors focused on prenatal development. In Arx mutants, the dorsal striatum was diminished and lacked cholinergic and GABAergic interneurons; the dorsal striatum was even more severely affected. In the mutants, radial and tangential migration from LGE and MGE was reduced, causing periventricular accumulation of immature neurons. In vitro experiments suggested that the migration defect was likely cell autonomous.