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Tuberous sclerosis is a developmental genetic disorder caused by mutations in TSC1, which results in epilepsy, autism, and intellectual disability. The cause of these neurological deficits remains unresolved. Imaging studies suggest that the thalamus may be affected in tuberous sclerosis patients, but this has not been experimentally interrogated. We hypothesized that thalamic deletion of Tsc1 at...
Expression of the Down syndrome cell-adhesion molecule (Dscam) is increased in the brains of patients with several neurological disorders. Although Dscam is critically involved in many aspects of neuronal development, little is known about either the mechanism that regulates its expression or the functional consequences of dysregulated Dscam expression. Here, we show that Dscam expression levels serve...
Feedforward inhibition sharpens the precision of neurons throughout ascending auditory pathways, including the binaural neurons of the medial superior olive (MSO). However, the biophysical influence of inhibition is poorly understood, particularly at higher frequencies at which the relative phase of inhibition and excitation becomes ambiguous. Here, we show in gerbil MSO principal cells in vitro that...
Systems of coupled oscillators abound in nature. How they establish stable phase relationships under diverse conditions is fundamentally important. The mammalian suprachiasmatic nucleus (SCN) is a self-sustained, synchronized network of circadian oscillators that coordinates daily rhythms in physiology and behavior. To elucidate the underlying topology and signaling mechanisms that modulate circadian...
Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed an approach, targeted recombination in active populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreER T2 is expressed in an activity-dependent...
During the formation of neuronal circuits, axon pathfinding decisions specify the location of synapses on the correct brain side and in correct target areas. We investigated a possible link between axon midline crossing and the subsequent development of output synapses formed by these axons. Conditional knockout of Robo3 in the auditory system forced a large commissural synapse, the calyx of Held,...
In this issue of Neuron, McGinty et al. (2013) report that the activity of cue-responsive neurons in the rat nucleus accumbens predicts the vigor of the subsequent approach movement. The characterization of this network state between motivation and action lends novel mechanistic insight to a spectrum of cue-elicited behaviors.
G protein-coupled receptors (GPCRs) affect many physiological processes by modulating both intrinsic membrane conductances and synaptic transmission. This study describes spontaneous miniature inhibitory postsynaptic currents mediated by vesicular dopamine release acting locally on metabotropic D 2 receptors leading to the activation of a G protein-coupled inwardly rectifying potassium conductance...
Neural networks are more than the sum of their parts, but the properties of those parts are nonetheless important. For instance, neuronal properties affect the degree to which neurons receiving common input will spike synchronously, and whether that synchrony will propagate through the network. Stimulus-evoked synchrony can help or hinder network coding depending on the type of code. In this Perspective,...
Neurons in the medial superior olive (MSO) enable sound localization by their remarkable sensitivity to submillisecond interaural time differences (ITDs). Each MSO neuron has its own “best ITD” to which it responds optimally. A difference in physical path length of the excitatory inputs from both ears cannot fully account for the ITD tuning of MSO neurons. As a result, it is still debated how these...
Available methods for differentiating human embryonic stem cells (ESCs) and induced pluripotent cells (iPSCs) into neurons are often cumbersome, slow, and variable. Alternatively, human fibroblasts can be directly converted into induced neuronal (iN) cells. However, with present techniques conversion is inefficient, synapse formation is limited, and only small amounts of neurons can be generated....
Commissural axons cross the nervous system midline and connect to targets in the contralateral hemisphere. In this issue of Neuron, Michalski et al. (2013) demonstrate that synapses formed by ipsilaterally misrouted commissural axons exhibit defects in synapse maturation. Thus, midline crossing primes axons for subsequent synaptogenesis.
A key function of the nucleus accumbens is to promote vigorous reward seeking, but the corresponding neural mechanism has not been identified despite many years of research. Here, we study cued flexible approach behavior, a form of reward seeking that strongly depends on the accumbens, and we describe a robust, single-cell neural correlate of behavioral vigor in the excitatory response of accumbens...
We developed a screening method for orphan receptor ligands, in which cell-surface proteins are expressed in Drosophila embryos from GAL4-dependent insertion lines and ligand candidates identified by the presence of ectopic staining with receptor fusion proteins. Stranded at second (Sas) binds to the receptor tyrosine phosphatase Ptp10D in embryos and in vitro. Sas and Ptp10D can interact in trans...
The encoding of long-term associative memories for learned behaviors is a fundamental brain function. Yet, how behavior is stably consolidated and retrieved in the vertebrate cortex is poorly understood. We trained zebrafish in aversive reinforcement learning and measured calcium signals across their entire brain during retrieval of the learned response. A discrete area of dorsal telencephalon that...
Highly topographic organization of neural circuits exists for the regulation of various brain functions in corticobasal ganglia circuits. Although neural circuit-specific refinement during synapse development is essential for the execution of particular neural functions, the molecular and cellular mechanisms for synapse refinement are largely unknown. Here, we show that protocadherin 17 (PCDH17),...
Animals undergo periods of behavioral quiescence and arousal in response to environmental, circadian, or developmental cues. During larval molts, C. elegans undergoes a period of profound behavioral quiescence termed lethargus. Locomotion quiescence during lethargus was abolished in mutants lacking a neuropeptide receptor (NPR-1) and was reduced in mutants lacking NPR-1 ligands (FLP-18 and FLP-21)...
The auditory system computes sound location by detecting submillisecond time differences in the arrival of sound at the two ears. Studies by van der Heijden et al. (2013) and Roberts et al. (2013) in this issue of Neuron shed light on how this is accomplished by the interaction of excitatory and inhibitory synapses.
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