Volume 17 Issue 8, August 2014

Does cell-to-cell spreading of misfolded proteins occur in all neurodegenerative disorders? A study in this issue of Nature Neuroscience now demonstrates propagation of mutant huntingtin in brain slice cultures and in vivo, thereby extending the process of cell-to-cell propagation of misfolded proteins to Huntington's disease.

Molecular orchestration mediated by Fezf2, a master transcriptional regulator of a particular type of cortical neurons, directly determines both their identity and axonal routing, and thus their connectivity.

Neural activity up to 3 mm deep in mouse brain can now be inhibited optogenetically through the intact cranium with a red-shifted opsin called Jaws.

Brain–machine interfaces provide not only potential therapies, but also new tools for studying neuronal processing. A study now uses them to investigate how learning affects sleep activity in motor cortex.

The authors review studies of basal ganglia (BG) physiology in the context of the indirect/direct pathway model of the BG. Noting work that is inconsistent with an exclusive role of the direct pathway in promoting movement and indirect pathway inhibiting movement, they propose a revision of the model incorporating recent findings.

In this paper, Womelsdorf and colleagues review the recent advances in our understanding of how rhythmic activity across multiple frequency bands and brain areas affects neural computations. The authors suggest a dynamic tripartite motif framework that links the activity signatures of given circuits with their structural elements and the proposed computational output.

Neurons make homeostatic adjustments to the strength of their synapses on the basis of their activity levels. Here the authors show the microRNA miR-92a represses the translation of the AMPA receptor subunit GluA1 and that, during activity blockade, its levels are reduced to increase the incorporation of new AMPA receptors.

Sensitization leads to hyperalgesia and depends on mechanisms similar to those involved in memory formation. Here, Bonin and De Koninck find that hyperalgesia can be reversed by combining reactivation of peripheral afferents with spinal administration of a protein synthesis inhibitor, thereby identifying a spinal analogue of memory re-consolidation that enables erasing pain hypersensitivity.

Fezf2 (Fezl) is a transcription factor that specifies corticospinal motor neurons (CSMN) originating from cortical layer 5b. Lodato et al. use cortical progenitor isolation from developing mouse brain and gene expression profiling to identify genes downstream of Fezf2 and demonstrate co-regulation of CSMN gene ensembles by Fezf2 in establishing CSMN cell identity.

Nuclear calcium levels affect gene expression, but little is known about how they are regulated. The authors show that large-conductance calcium-activated potassium (BK) channels are present on the nuclear envelope in rodent hippocampal neurons. Blockade of nuclear BK channels revealed that they regulate nucleoplasmic Ca²⁺, gene expression and dendritic arborization.

Trans-neuronal transfer of pathogenic proteins has been demonstrated in multiple neurodegenerative diseases. Here the authors show in vitro and in a mouse model that mutant Huntingtin is also transferred from one neuron to another. This transfer requires exocytosis machinery and contributes to neurodegeneration.

The authors show that phosphorylation of the translation factor eIF2α is necessary and sufficient for mGluR-LTD. They identify mRNAs that are translated during mGluR-LTD and regulated by p-eIF2α, including Ophn1 as a key target. Deficient p-eIF2α-mediated translation impairs object-place learning, which requires mGluR-LTD. eIF2α phosphorylation may determine whether synapses undergo LTD or LTP.

Exposure to psychostimulants such as cocaine induces synaptic plasticity within the nucleus accumbens (NAc) and alters behavior. Here the authors find a new role for the acid-sensing channel 1A (ASIC1A) in excitatory transmission and plasticity within the NAc that contributes to cocaine-induced learning and self-administration.

In this study, the authors show that neural correlates of insight, including synaptic efficacy in the orbitofrontal cortex (OFC), are lost in rodents which are allowed to self-administer cocaine, suggesting a link between drug use and adaptation to changing circumstances. Optogenetic activation of OFC pyramidal neurons was able to rescue these behaviors.

In this study, the authors simultaneously recorded multiple neurons from the anterior cingulate cortex (ACC) and the dorsal striatum (DS) as rats performed an action sequencing task. Sequence and lever decoding based on individual neuron activity was similar in the two regions, but decoding at the ensemble level was quite different.

Using a rodent neuroprosthetic model, the authors found that, after successful learning, task-related units specifically experienced increased locking and coherency to SWA during sleep, and spike-spike coherence among these units was significantly enhanced. These changes were not present with poor skill acquisition or after control awake periods, demonstrating specificity to learning.

The authors found human neuroimaging evidence that entire valence spectrum is represented as a collective pattern in regional neural activity, with sensory-specific signals in the ventral temporal and anterior insular cortices and abstract codes in the orbitofrontal cortices. In this way, the subjective quality of affect can be objectively quantified across stimuli, modalities and people.

In this Technical Report, Chuong and colleagues introduce Jaws, an archaeon-derived, photoactivatable chloride pump that responds to red light. Owing to its efficiency in absorbing red photons and its large photocurrent, Jaws can be transcranially activated deep in the brain and thus allows noninvasive optogenetic silencing.

This Technical Report describes new methods of transcranial magnetic stimulation (TMS) in non-human primates. By combining single neuron recording with a modified TMS coil with focused stimulation in alert macaques, the authors show that this method can reduce stimulation artifact and allow investigation into the neuronal mechanisms of TMS.