Interactions between specialized gain control mechanisms in olfactory processing.

Gain control is a process that adjusts a system's sensitivity when input levels change. Neural systems contain multiple mechanisms of gain control, but we do not understand why so many mechanisms are needed or how they interact. Here, we investigate these questions in the Drosophila antennal lobe, where we identify several types of inhibitory interneurons with specialized gain control functions. We find that some interneurons are nonspiking, with compartmentalized calcium signals, and they specialize in intra-glomerular gain control. Conversely, we find that other interneurons are recruited by strong and widespread network input; they specialize in global presynaptic gain control. Using computational modeling and optogenetic perturbations, we show how these mechanisms can work together to improve stimulus discrimination while also minimizing temporal distortions in network activity. Our results demonstrate how the robustness of neural network function can be increased by interactions among diverse and specialized mechanisms of gain control.

Dopamine promotes head direction plasticity during orienting movements.

In neural networks that store information in their connection weights, there is a tradeoff between sensitivity and stability1,2. Connections must be plastic to incorporate new information, but if they are too plastic, stored information can be corrupted. A potential solution is to allow plasticity only during epochs when task-specific information is rich, on the basis of a 'when-to-learn' signal3. We reasoned that dopamine provides a when-to-learn signal that allows the brain's spatial maps to update when new spatial information is available-that is, when an animal is moving. Here we show that the dopamine neurons innervating the Drosophila head direction network are specifically active when the fly turns to change its head direction. Moreover, their activity scales with moment-to-moment fluctuations in rotational speed. Pairing dopamine release with a visual cue persistently strengthens the cue's influence on head direction cells. Conversely, inhibiting these dopamine neurons decreases the influence of the cue. This mechanism should accelerate learning during moments when orienting movements are providing a rich stream of head direction information, allowing learning rates to be low at other times to protect stored information. Our results show how spatial learning in the brain can be compressed into discrete epochs in which high learning rates are matched to high rates of information intake.

DEG/ENaC/ASIC channels vary in their sensitivity to anti-hypertensive and non-steroidal anti-inflammatory drugs.

The degenerin channels, epithelial sodium channels, and acid-sensing ion channels (DEG/ENaC/ASICs) play important roles in sensing mechanical stimuli, regulating salt homeostasis, and responding to acidification in the nervous system. They have two transmembrane domains separated by a large extracellular domain and are believed to assemble as homomeric or heteromeric trimers. Based on studies of selected family members, these channels are assumed to form nonvoltage-gated and sodium-selective channels sensitive to the anti-hypertensive drug amiloride. They are also emerging as a target of nonsteroidal anti-inflammatory drugs (NSAIDs). Caenorhabditis elegans has more than two dozen genes encoding DEG/ENaC/ASIC subunits, providing an excellent opportunity to examine variations in drug sensitivity. Here, we analyze a subset of the C. elegans DEG/ENaC/ASIC proteins to test the hypothesis that individual family members vary not only in their ability to form homomeric channels but also in their drug sensitivity. We selected a panel of C. elegans DEG/ENaC/ASICs that are coexpressed in mechanosensory neurons and expressed gain-of-function or d mutants in Xenopus laevis oocytes. We found that only DEGT­1d, UNC­8d, and MEC­4d formed homomeric channels and that, unlike MEC­4d and UNC­8d, DEGT­1d channels were insensitive to amiloride and its analogues. As reported for rat ASIC1a, NSAIDs inhibit DEGT­1d and UNC­8d channels. Unexpectedly, MEC­4d was strongly potentiated by NSAIDs, an effect that was decreased by mutations in the putative NSAID-binding site in the extracellular domain. Collectively, these findings reveal that not all DEG/ENaC/ASIC channels are amiloride-sensitive and that NSAIDs can both inhibit and potentiate these channels.

A Neural Network for Wind-Guided Compass Navigation.

Spatial maps in the brain are most accurate when they are linked to external sensory cues. Here, we show that the compass in the Drosophila brain is linked to the direction of the wind. Shifting the wind rightward rotates the compass as if the fly were turning leftward, and vice versa. We describe the mechanisms of several computations that integrate wind information into the compass. First, an intensity-invariant representation of wind direction is computed by comparing left-right mechanosensory signals. Then, signals are reformatted to reduce the coding biases inherent in peripheral mechanics, and wind cues are brought into the same circular coordinate system that represents visual cues and self-motion signals. Because the compass incorporates both mechanosensory and visual cues, it should enable navigation under conditions where no single cue is consistently reliable. These results show how local sensory signals can be transformed into a global, multimodal, abstract representation of space.

Sensorimotor experience remaps visual input to a heading-direction network.

In the Drosophila brain, 'compass' neurons track the orientation of the body and head (the fly's heading) during navigation 1,2. In the absence of visual cues, the compass neuron network estimates heading by integrating self-movement signals over time3,4. When a visual cue is present, the estimate of the network is more accurate1,3. Visual inputs to compass neurons are thought to originate from inhibitory neurons called R neurons (also known as ring neurons); the receptive fields of R neurons tile visual space5. The axon of each R neuron overlaps with the dendrites of every compass neuron6, raising the question of how visual cues are integrated into the compass. Here, using in vivo whole-cell recordings, we show that a visual cue can evoke synaptic inhibition in compass neurons and that R neurons mediate this inhibition. Each compass neuron is inhibited only by specific visual cue positions, indicating that many potential connections from R neurons onto compass neurons are actually weak or silent. We also show that the pattern of visually evoked inhibition can reorganize over minutes as the fly explores an altered virtual-reality environment. Using ensemble calcium imaging, we demonstrate that this reorganization causes persistent changes in the compass coordinate frame. Taken together, our data suggest a model in which correlated pre- and postsynaptic activity triggers associative long-term synaptic depression of visually evoked inhibition in compass neurons. Our findings provide evidence for the theoretical proposal that associative plasticity of sensory inputs, when combined with attractor dynamics, can reconcile self-movement information with changing external cues to generate a coherent sense of direction7-12.