Theoretical study offers a new understanding of the neural basis of expectation (1 Apr 2019)
It is known that sensory stimuli – especially powerful ones like taste – are affected by expectation, which is a trigger to improving stimuli detection, distinction and reaction. Yet, scientists know little about how expectation shapes the cortical processes of sensory information. Now Luca Mazzucato, Giancarlo La Camera and Alfredo Fontanini have developed a theoretical model of how the primary gustatory cortex can mediate the expectation of receiving a taste. In a paper published in Nature Neuroscience, the researchers demonstrate that expectation is mediated by an acceleration of the neural activity generated by certain populations of neurons. In the gustatory cortex and other areas of the brain, neural acivity unfolds as a sequence of metastable states (see figure below). Some states convey information on specific stimuli and therefore the authors have dubbed them 'coding states'. When the neural activity lands (albeit transiently) on a coding state, processing of the corresponding stimulus is faster. The model explains also how the faster onset of coding states is due to the anticipatory cue used in experiment to signal the forthcoming delivery of a taste. Although the empirical demonstration of the principle was performed in the gustatory cortex, the model may go beyond taste processing as it posits, as a general theory, that expectations can be mediated by a change in the dynamics of cortical circuits.
This color-coded raster plot reveals spiking activity of nine neurons in the gustatory cortex. Every time a color changes, it means that one or more neurons have become more or less active, which indicate a change in neural states. Accoding to a new model, t hese states and their duration are altered by expectation.
Disease-associated mutations offer new clues to protein function (14 Sept 2018)
NMDA receptors are transmembrane proteins that help regulate our memories and behavior. Random changes in the genes encoding NMDA receptor subunits, yielding de novo missense mutations, are associated with epilepsy, autism spectrum disorder, intellectual disability, and schizophrenia. The most prevalent site at which missense mutations occur in NMDA receptors is at a conserved glycine in the transmembrane region forming the ion channel. In a recent paper published in Nature Communications, Lonnie Wollmuth's group has shown that this glycine works in an unanticipated way: it acts as a pivot point or hinge which allows for expansion of the inner part of the ion channel enhancing NMDA receptor signaling. Disease-associated mutations prevent this movement and, hence, normal NMDA receptor signaling. These insights suggest new strategies for targeting NMDA receptors in the treatment of neurological disorders.
Expansion of the inner pore permitted mainly by the GluN1 M4 conserved glycine facilitates NMDA receptor gating and Ca2+ permeation.
Measures of traumatic stress exposure based on changes in gene regulatory function (23 Aug 2018)
Surprisingly, given the well established deleterious effects of traumatic stress exposure, there is no simple, or even complex, way to objectively measure the level of traumatic stress to which an individual has been exposed. A molecular diagnostic tool that could robustly measure levels of traumatic stress exposure would be of considerable value in assessing the risk of developing post-traumatic stress disorder or stress-induced depression after exposure to stressful events. In a recent paper published in Translational Psychiatry, Drs. McKinnon and Rosati's group has shown that the gene regulatory network encodes sufficient information to reliably distinguish unstressed individuals from those who have been exposed to traumatic stress. These results suggest that it is possible to create diagnostic measures of stress exposure using molecular markers from the gene regulatory network.