Articles in 2015

Seeking insight into dopamine's contribution to motivation and learning, the authors examined dopamine release in the rat nucleus accumbens during adaptive decision-making. Dopamine levels convey a running estimate of available future reward, which is used to decide whether it's worthwhile to engage in a behavioral task. Abrupt fluctuations serve as reward prediction errors, reinforcing behavioral choices.

Although attentional abilities vary widely and have profound everyday effects, a standardized measure of these abilities is lacking. This study introduces a new fMRI measure based on patterns of whole-brain connectivity, which predicts adults' attention performance and children's ADHD symptoms from data acquired while individuals are resting in the scanner.

The c-fos gene is induced by a broad range of stimuli and is commonly used as a reliable marker for neural activity. The authors demonstrate that the combinatorial activation of multiple enhancers surrounding the c-fos gene is a critical mechanism of ensuring robust c-fos gene induction in response to various stimuli.

This study examines the effect of categorization-task training on parietal (PPC) and prefrontal (PFC) activity and finds a learning-dependent emergence of memory-related delay activity in PPC, whereas PFC shows delay-period selectivity both before and after categorization training. This reveals distinct roles of PFC and PPC in short-term working memory.

Using fMRI multi-voxel pattern decoding, human superior IPS, but not occipital cortex, was found to closely track behavioral measures of information storage in visual short-term memory (VSTM) across distractor presence and predictability. This suggests that superior IPS, and not occipital cortex, has a central role in VSTM storage in the human brain.

Synaptic adhesion molecules are known to regulate synapse development, but growing evidence indicates that they also regulate synaptic function and plasticity. The authors report a novel synaptic adhesion molecule, IgSF11, that regulates excitatory synaptic transmission and plasticity through its dual interaction with the postsynaptic scaffold PSD-95 and AMPA receptors.

The authors applied a correlation-based metric, ‘differential stability’ (DS), to assess reproducibility of gene expression patterning across individual brains, revealing mesoscale genetic organization. The highest DS genes were enriched for brain-related biological annotations, disease associations and drug targets, and their anatomical expression pattern correlated with resting state functional connectivity.

Via exome sequencing, the authors identified mutations in the NONO protein, a member of the DBHS family, as a likely cause of severe intellectual disability. Using animal and cell models, they found that nearly one-third of NONO-regulated transcripts were synaptosomal and that NONO depletion directly affected inhibitory synaptic structure.

Generalizing from past events to novel situations is common in animals. To have an adaptive value, this ability requires flexible control, especially in fearful situations. The authors demonstrate that fear generalization can be broken down to neural mechanisms involved separately in the detection of threat and its uncertainty.

Immunotherapy with antibodies targeting the amyloid-β peptide has yet to show any cognitive benefit in Alzheimer's disease patients in clinical trials. In vivo two-photon imaging in mouse models of Alzheimer's disease now reveals that these antibodies do not alleviate neuronal dysfunction and can even worsen it.

The authors developed two subcellular optogenetic tools, pHoenix and lyso-pHoenix, that allow light-driven acidification of synaptic vesicles and lysosomes, respectively. pHoenix was used to control the degree of neurotransmitter uptake into synaptic vesicles, revealing that exocytosis of partially filled vesicles is less efficient than the release of completely filled vesicles.

Chronic neuropathic pain is associated with K⁺ channel downregulation in primary sensory neurons. The authors show that G9a, a histone-modifying enzyme, is required for transcriptional repression of K⁺ channel–associated gene families caused by nerve injury. G9a in primary sensory neurons is a key epigenetic regulator involved in acute-to-chronic pain transition.

To learn, the brain must be able to tell when it has made a mistake. A new study by Ohmae and Medina reveals the neural algorithm responsible for encoding error signals during cerebellar learning. A replica of this algorithm was previously found in dopamine neurons, suggesting the same elemental mechanism.

Proprioception, the sense of body and limb position, begins in nerve cells called proprioceptors that are activated by muscle or joint stretch. The molecular mechanism of mechanotransduction in mammalian proprioceptors is unknown. The authors show that the mechanically activated cation channel Piezo2 is the principal mechanotransducer in murine proprioceptors.

A cortical parcellation technique accurately maps functional organization in individual brains. Functional networks mapped by this approach are highly reproducible and effectively capture individual variability. The algorithm performs well across different populations and data types and is validated by invasive cortical stimulation mapping in surgical patients.

Endogenous neural stem cells in the adult hippocampus are generally considered to be bi-potent. The authors show in mouse that inactivation of neurofibromin 1 (Nf1), a gene that is mutated in neurofibromatosis type 1, unlocks a latent oligodendrocyte lineage potential of neural stem cells to produce all three lineages in vivo.

Orientation selectivity is a key property of neurons in the primary visual cortex. Using genetic silencing of cortical neurons throughout development, this study shows that initial formation of orientation selectivity is independent of neuronal activity. The initial selectivity is subsequently modified and this later process depends on spontaneous neuronal activity.

Optogenetic release of dopamine from midbrain inputs to the hippocampus produces a powerful bidirectional control over hippocampal information flow to CA1 pyramidal neurons that depends on the pattern of stimulation. In this manner, a switch in the state of dopaminergic activity may serve to select specific events for memory storage.

The authors performed a comprehensive proteome analysis of the adult mouse brain, its major regions and CNS cell types at a depth of >13,000 proteins. This new resource represents the largest collection of cell type–resolved protein expression data of the brain. The power of the data set was illustrated by identifying novel adhesion molecules in glia and neuron interaction.

Experience-dependent synaptic modifications are one of the fundamental mechanisms of learning and memory, yet they are difficult to measure in vivo. Here the authors introduce a network model–based method that infers synaptic plasticity rules from the analysis of the statistics of neuronal responses to novel versus familiar stimuli.