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C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. With unbiased screens in Saccharomyces cerevisiae, Jovicic et al. identified potent modifiers of toxicity of dipeptide repeat proteins produced by unconventional translation of the C9orf72 repeat expansions, pointing to nucleocytoplasmic transport impairments as potential disease mechanisms.
Over the past decade, modern optogenetics has emerged from the convergence of developments in microbial opsin engineering, genetic methods for targeting, and optical strategies for light delivery. In this Historical Commentary, Karl Deisseroth reflects on the optogenetic landscape, from the important steps but slow progress in the beginning to the acceleration in discovery seen in recent years.
On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique.
The locus coeruleus is a major neuromodulatory center for the mammalian brain. Here, the authors show that presenting sounds when locus coeruleus is active leads to enduring modifications of responses in auditory cortex and locus coeruleus. These synaptic and spiking changes have a profound effect on auditory perception for weeks.
The optimal disambiguation of similar sensory stimuli by neuronal networks is essential to adapt animal behavior. Gschwend and colleagues show that the olfactory bulb network acts as a pattern separator, increasing slight differences between highly related odors. Inhibitory interneuron activation causally improves pattern separation and facilitates odor discrimination learning.
Memory formation requires gene transcription, but the link between synaptic activity and transcription is not fully understood. Brd4 regulates transcription in other cell types and Brd4 family inhibitors are in clinical trials for cancer. The authors show that Brd4 is important for activity-dependent gene transcription in neurons and memory consolidation.
Some stress-related memories are state-dependent: they cannot be retrieved unless the brain is in the same state as during initial encoding. The authors show that hippocampal extrasynaptic GABAA receptors, regulated by miR-33, support state-dependent contextual fear conditioning by altering the processing of context memories within the extended hippocampal circuit.
This study shows conserved EAG2 potassium channel function in brain tumorigenesis and metastasis, cooperation of different potassium channels for mitotic volume regulation, and EAG2 enrichment at the trailing edge for local volume regulation and cell motility. The authors identified the FDA-approved drug thioridazine as an EAG2 blocker of potential therapeutic value.
GFP reporter lines are useful for labeling specific cell types. Here, the authors developed a method to convert GFP expression directly into Cre recombinase activity. GFP-dependent Cre was delivered via electroporation or AAV to neural tissues in the mouse, and could be used for optogenetic control of specific cell types.
This study examines how key inputs to a brain area vital for song production can interact cooperatively to change each other. The authors show that naturalistic stimulation patterns drive bidirectional in vitro plasticity in synaptic inputs to a song production area, and use this understanding to manipulate song plasticity in vivo.
Using in vivo imaging, the authors explore how dopamine loss in Parkinson’s disease mouse models affects synaptic plasticity in motor cortex. They find that dopamine D1 and D2 receptor signaling distinctly regulates dendritic spine dynamics and that dopamine loss results in atypical synaptic adaptations. These mechanisms may contribute to impaired motor performance in Parkinson's disease.
By recording from cerebellar output neurons during motor learning, the authors provide direct evidence for an elegant computation requiring the comparison of predicted and actual sensory feedback to signal unexpected sensation. Their results suggest that rapid updating of the cerebellum's internal model enables the brain to learn to expect unexpected sensory input.
The authors show that fruit flies briefly silence visual processing during voluntary flight turns, which likely helps flies to ignore the image of the world sweeping over the retina during such turns.
The authors report that the ultrastructure and plasticity of excitatory synapses connecting dentate gyrus and CA3 of the hippocampus are severely compromised in a transchromosomic mouse model of Down syndrome. These alterations are accompanied by unstable information coding by CA3 and CA1 place cells, which may contribute to aspects of impaired cognition in the disease.
Humans learn about people and objects through positive and negative experiences, yet they can look beyond rewards to encode trait-level attributes such as generosity. The authors show that neural activity and choices reflect feedback-based learning about rewards and traits of people and slot machines and that trait learning strongly drives decisions about new social interactions.
A study finds that pain hypersensitivity in male and female mice is differentially dependent on microglia and T cells, and describes a sex-specific response to microglia-targeted pain treatments. This sex difference will be important to consider when developing treatments for pain and other neurological disorders involving microglia and immune cells.
How do neurons combine distinct information streams and form long-lasting associations? Dendritic plateau potentials may allow the integration and storage of coincident location and contextual information in hippocampal neurons.
The confidence that we place in our decisions can affect the judgments themselves. The BOLD signal in ventromedial prefrontal cortex automatically reflects the relationship between confidence and judgments on a range of tasks.
