Cellular/Molecular 0
Role of IK0D 0 in Temperature Sensitivity
Rodolfo Madrid, Elvira de la Peña, Tansy Donovan-Rodriguez, Carlos Belmonte, and Félix Viana
(see pages 3120–3131)
Pleasant cool and unpleasant cold sensations are thought to be mediated by distinct groups of peripheral thermoreceptor neurons that start spiking at different temperatures. The cold-sensitive transient receptor potential channel TRPM8 is present in these neurons, but if and how this channel alone can produce disparate thermal thresholds is not clear. This week, Madrid et al. suggest that slowly inactivating voltage-sensitive potassium channel currents (IKD), which are activated near resting membrane potentials, counteract TRPM8 currents and thereby help determine the temperature threshold in mouse trigeminal ganglion neurons. Cold-sensitive neurons that start spiking at warmer temperatures (31°C) had larger TRPM8-mediated currents and smaller IKD than neurons that started spiking at colder temperatures (24°C). Blocking TRPM8 channels shifted temperature threshold to colder temperatures, whereas blocking IKD shifted threshold to warmer temperatures. Moreover, when an IKD blocker was injected into the paw of mice, normally innocuous cool stimuli elicited nociceptive behaviors, suggesting IKD decreases cold sensitivity in vivo.
Development/Plasticity/Repair
Training-Induced Changes in Brain Morphology
Krista L. Hyde, Jason Lerch, Andrea Norton, Marie Forgeard, Ellen Winner, Alan C. Evans, and Gottfried Schlaug
(see pages 3019–3025)
Several studies have suggested that training induces structural changes in the brain. In some cases, however (e.g., studies of adult musicians versus nonmusicians), it is not clear whether differences are the result of training or instead underlie an innate predisposition to seek or persevere in training. To address this question, Hyde et al. used automated magnetic-resonance-imaging-based morphometric analyses to compare the brains of 6-year-old children before and after half of them received keyboard training. All children exhibited normal developmentally related increases in voxel size in some regions, but those that received musical training showed additional increases in motor and primary auditory cortex. These changes were correlated with improvements in specific fine-motor and auditory-discrimination skills. Musical training did not produce significant improvements in nonmusical cognitive skills as previously proposed. Interestingly, however, significant enlargements occurred in frontomesial and posterior pericingulate areas, suggesting that functions performed by these areas may be enhanced by musical training.
Behavioral/Systems/Cognitive
Effects of Dopamine on fMRI Signals
Yen-Yu I. Shih, Chiao-Chi V. Chen, Bai-Chuang Shyu, Zi-Jun Lin, Yun-Chen Chiang, Fu-Shan Jaw, You-Yin Chen, and Chen Chang
(see pages 3036–3044)
Functional magnetic resonance imaging (fMRI) measures changes in blood flow, volume, or oxygenation levels; and because neuronal activity generally induces local increases in blood flow, fMRI is used to identify areas of neural activity. But proper interpretation of fMRI data requires a full understanding of the relationship between neural activity and hemodynamic responses. Although experimental evidence supports the view that increases in fMRI signals reflect local synaptic activation, the neurophysiological underpinnings of decreases in fMRI signals are less clear. In addition, direct vasoconstrictive effects of neurotransmitters can complicate the interpretation of fMRI data. Shih et al. used electrical paw stimulation in rats to induce dopamine release in the striatum. Electrophysiological recordings indicated that the stimulation increased neural activity in primary somatosensory cortex and striatum. As expected, neural activity was correlated with increased cerebral blood volume (CBV) in somatosensory cortex. But in striatum, CBV decreased, demonstrating that neural activity is not unambiguously reflected by fMRI.
Electrical stimulation of paw (top) decreased CBV in the striatum (red) and increased CBV in the primary somatosensory cortex (blue). Intravenous injection of a dopamine D2 receptor antagonist (bottom) eliminated stimulation-induced changes in striatum, but not in somatosensory cortex.
Neurobiology of Disease
AChR Subunits Involved in Nicotine Withdrawal
Ramiro Salas, Renea Sturm, Jim Boulter, and Mariella De Biasi
(see pages 3014–3018)
Quitting tobacco use is difficult not only because it requires giving up the rewarding properties of nicotine, but also because nicotine withdrawal produces unpleasant effects such as anxiety, irritability, and weight gain. Reward and withdrawal effects may be mediated by different subsets of nicotinic acetylcholine receptors (nAChRs) in different regions of the brain. For example, reward requires expression of β2 subunits in the ventral tegmental area (VTA), whereas withdrawal requires β4 subunits, which are highly expressed in the medial habenula (mHb) and intrapeduncular nucleus (IPN). Salas et al. have extended these results, reporting that in mice chronically treated with nicotine, nAChR antagonists precipitated withdrawal symptoms when injected into the mHb or IPN, but not when injected into the cortex, hippocampus, or VTA. In addition, somatic signs of withdrawal (e.g., increased scratching and shaking) were eliminated in mice lacking α2 or α5 subunits, both of which are highly expressed in the IPN.
