Volume 18 Issue 9, September 2015

Reflexes help us maintain a default posture and direction of locomotion. But what if we deliberately want to move differently? In Drosophila, the brain modifies a visually driven stabilization reflex to enable voluntary movements.

Our internal states can color our memories just as powerfully as the external environment. A study finds that hippocampal GABA_A receptors and associated microRNAs are important for generating state-dependent contextual fear memories.

Dopamine loss in Parkinson's disease affects not only the basal ganglia, but also motor cortex, causing a surprising increase of spine turnover in the cortical dendritic tree and altering synaptic plasticity and memory retention.

How do individuals attribute dispositional properties, or traits, to others? A study suggests that associative learning processes underlie aspects of trait learning at both neural and behavioral levels.

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.

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.

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.

It is widely assumed that D1 and D2 dopamine receptor-expressing striatal neurons code for discrete pathways in the basal ganglia. Combining optogenetics and electrophysiology, the authors show that this output architecture does not apply to nucleus accumbens neurons. Current thinking attributing D1/D2 selectivity to accumbens projections thus should be reconsidered.

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.

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.

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 show that the neuron-specific LSD1 variant (LSD1n) promotes transcription initiation and elongation in response to neuronal activity. LSD1n is essential for spatial learning and long-term memory formation. LSD1n exhibits novel substrate specificity for histone H4 K20 methylation.

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 GABA_A 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 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 a combination of electrophysiological and neurochemical techniques the authors report that deep and superficial CA1 pyramidal neurons behave differently during hippocampal sharp-wave ripples, with deep cells becoming hyperpolarized and superficial cells undergoing depolarization. The study also reveals some of the microcircuit mechanisms that underlie this spatiotemporal specialization, including the involvement of CA2 pyramidal cells and the role of perisomatic inhibition.

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.

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.

Humans have a capacity for hierarchical cognitive control—the ability to simultaneously control immediate actions while holding more abstract goals in mind. The authors show that neural oscillations establish dynamic communication networks within the frontal cortex and that these oscillations coordinate local neural activity with increasing cognitive control.

To elucidate novel molecular mechanisms underlying neurodegeneration in Parkinson's disease, the authors generated mice for cell type-specific profiling of dopaminergic neurons. Regulatory network analysis of translatome libraries from dopaminergic neurons under degenerative stress facilitated the identification of intrinsic upstream regulators that oppose degeneration. This strategy can be generalized to investigate degeneration of other classes of neurons.

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.

Ten years ago, channelrhodopsin-2 was expressed in neurons and shown to control their activity. In this issue, we consider how the field has developed since these early optogenetic experiments.