Volume 18 Issue 12, December 2015

Previous studies have reported 'preplay' of hippocampal neural activity patterns associated with events yet to occur. Silva et al. challenge this finding on the basis of large-scale recordings before and after experiences.

Previous work has suggested that cortical recurrent circuits can self-sustain their activity without thalamic input. A study now demonstrates that this is not the case in the awake brain, which tightly locks cortical timing to thalamic activity.

Synaptic plasticity during learning is as fundamental as it is hard to study. The underlying synaptic plasticity rule has now been inferred using only the firing rate statistics of visual neurons in monkeys before and after learning.

Recent research on disparate psychiatric disorders has implicated rare variants in genes involved in global gene regulation and chromatin modification, as well as many common variants located primarily in regulatory regions of the genome. Understanding precisely how these variants contribute to disease will require a deeper appreciation for the mechanisms of gene regulation in the developing and adult human brain. The PsychENCODE project aims to produce a public resource of multidimensional genomic data using tissue- and cell type–specific samples from approximately 1,000 phenotypically well-characterized, high-quality healthy and disease-affected human post-mortem brains, as well as functionally characterize disease-associated regulatory elements and variants in model systems. We are beginning with a focus on autism spectrum disorder, bipolar disorder and schizophrenia, and expect that this knowledge will apply to a wide variety of psychiatric disorders. This paper outlines the motivation and design of PsychENCODE.

Neurons receive synaptic input primarily onto their dendrites. This review focuses on how synaptic inputs are integrated by dendrites, with an emphasis on recent work in the intact brain. It describes the range of computations dendrites perform on their inputs, highlighting their critical role in information processing in the brain.

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.

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.

Using functional MRI and a novel model-based analysis, the authors find that the uncertainty in sensory representations can reliably be estimated from trial-by-trial activity in human visual cortex. Moreover, this uncertainty represented in cortical activity affects the way people make decisions.

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.

Stroke is the leading cause of adult disability. This study shows that the secreted factor GDF10 is a signal for the formation of new brain connections that lead to recovery after stroke and can be manipulated to enhance recovery and movement control in this disease.

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.

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.

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.

Hippocampal place cells are active offline in ‘replay’ sequences reflecting speeded-up depictions of behavioral trajectories, suggesting a model of memory. The authors show that encoding of replay sequences requires behavioral experience and the activation of molecular mechanisms of synaptic plasticity, while retrieval does not.

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.

By optogenetically silencing thalamus, the authors show that visual cortex does not sustain a response without thalamus for more than a few tens of milliseconds. This rapid cortical activity decay predicts the temporal dynamics of sensory activity transmission between thalamus and cortex in awake animals, whereas under anesthesia, the fidelity of thalamo-cortical connection is dominated by the effect of synaptic depression.

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.

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.

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.

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.

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.

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.

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.