Research Highlights: In Brief...

BAC-driven miRNA gene expression knockdown

KA Garbett, S Horvath, PJ Ebert, MJ Schmidt, K Lwin, A Mitchell, P Levitt and K Mirnics (2010). Novel animal models for studying complex brain disorders: BAC-driven miRNA-mediated in vivo silencing of gene expression. Mol. Psychiatry. doi: 10.1038/mp.2010.1

Animal models of disease represent one of the most powerful methods of analyzing the pathophysiological mechanisms of genetic disorders. However, the development of such models is often time-consuming, complex, and carries nonspecific caveats, such as the imprecise deletion of a gene of choice. Using bacterial artificial chromosomes, cell-type specific promoters, a standard reporter, and a microRNA mechanism for gene silencing, Garbett et al. present a powerful mechanism to specifically reduce gene expression in vivo. As microRNAs are of small size, they anticipate that this new method could simultaneously silence multiple genes in a cell-type specific manner. Accordingly, these transgenic mice would allow exquisite precision in determining the effects of a given set of genes on the presentation of disease.


Pain Pathways: Neuropeptide Y may be targeted to relieve pain

RG Wiley, LL Lemons and RH Kline IV (2009). Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin. Neuroscience. 161 (1): 139-147.

There is an endless list of reasons why individuals seek treatment for pain, but the molecular mechanisms that underlie pain perception are unclear. Wiley et al. demonstrate how Neuropeptide Y (NPY) and its receptor Y1 (Y1R) function in the rodent spinal cord to mediate nociception. After intrathecal injection of saporin toxin conjugated to NPY to selectively kill Y1R-expressing neurons in the dorsal horn of the spinal cord, rats displayed an increased latency to withdraw their paws from noxious hot stimuli. The rodents also had a significant decrease in nocifensive behavior when presented with the hot stimuli or when injected with formalin in the plantar region of the hind paw, as measured by licking and guarding events. This toxin-based approach allows researchers to selectively examine groups of neurons involved in the perception of pain and tease apart each group’s contribution. These studies could prove to have a significant impact on the field of pain research and may provide researchers with some insight into alternative approaches to treat pain.


What’s unusual about that? Neural substrates for the detection of novel, unusual stimuli

Blackford JU, Buckholtz JW, Avery SN, Zald DH (2010). A unique role for the human amygdala in novelty detection. Neuroimage. 50(3):1188-93.

Novelty detection is an important trait in perceiving and responding to our environment. In particular novel, yet unusual or uncommon stimuli that are behaviorally salient can engage specific neural mechanisms involved in emotional learning and memory. In this study, the authors used functional magnetic resonance imaging to observe blood oxygen level dependent (BOLD) responses in the human amygdala and hippocampus when they presented participants with novel, common stimuli (e.g., chair, clock, tree) versus novel, unusual stimuli (e.g., Prague Dancing House, futuristic skyscraper, leafy sea dragon). Blackford and colleagues found that novel, common stimuli showed robust BOLD activation in both the amygdala and the hippocampus. However, only the amygdala showed a preferential activation for the novel, unusual stimuli, compared to the novel common stimuli. These results lead the authors to speculate that within the novelty detection circuit, the amygdala plays a distinct role in uniquely responding to a specific category of stimuli, namely those that are novel and unusual.