Population coding of auditory space in the dorsal inferior colliculus persists with altered binaural cues.

Sound localization is critical for real-world hearing, such as segregating overlapping sound streams. For optimal flexibility, central representations of auditory space must adapt to peripheral changes in binaural cue availability, such as following asymmetric hearing loss in adulthood. However, whether the mature auditory system can reliably encode spatial auditory representations upon abrupt changes in binaural input is unclear.

Mixed Representations of Sound and Action in the Auditory Midbrain.

Linking sensory input and its consequences is a fundamental brain operation. During behavior, the neural activity of neocortical and limbic systems often reflects dynamic combinations of sensory and task-dependent variables, and these "mixed representations" are suggested to be important for perception, learning, and plasticity. However, the extent to which such integrative computations might occur outside of the forebrain is less clear.

Sclerostin blockade inhibits bone resorption through PDGF receptor signaling in osteoblast lineage cells.

While sclerostin-neutralizing antibodies (Scl-Abs) transiently stimulate bone formation by activating Wnt signaling in osteoblast lineage cells, they exert sustained inhibition of bone resorption, suggesting an alternate signaling pathway by which Scl-Abs control osteoclast activity. Since sclerostin can activate platelet-derived growth factor receptors (PDGFRs) in osteoblast lineage cells in vitro and PDGFR signaling in these cells induces bone resorption through M-CSF secretion, we hypothesized that the prolonged anticatabolic effect of Scl-Abs could result from PDGFR inhibition. We show here that inhibition of PDGFR signaling in osteoblast lineage cells is sufficient and necessary to mediate prolonged Scl-Ab effects on M-CSF secretion and osteoclast activity in mice.

Auditory Corticofugal Neurons Transmit Auditory and Non-auditory Information During Behavior.

Layer 5 pyramidal neurons of sensory cortices project "corticofugal" axons to myriad sub-cortical targets, thereby broadcasting high-level signals important for perception and learning. Recent studies suggest as key biophysical mechanisms supporting corticofugal neuron function: these long-lasting events drive burst firing, thereby initiating uniquely powerful signals to modulate sub-cortical representations and trigger learning-related plasticity. However, the behavioral relevance of corticofugal dendritic spikes is poorly understood.

Calcium-Sensitive Subthreshold Oscillations and Electrical Coupling in Principal Cells of Mouse Dorsal Cochlear Nucleus.

In higher sensory brain regions, slow oscillations (0.5-5 Hz) associated with quiet wakefulness and attention modulate multisensory integration, predictive coding, and perception. Although often assumed to originate via thalamocortical mechanisms, the extent to which subcortical sensory pathways are independently capable of slow oscillatory activity is unclear.

Mixed representations of sound and action in the auditory midbrain.

Linking sensory input and its consequences is a fundamental brain operation. Accordingly, neural activity of neo-cortical and limbic systems often reflects dynamic combinations of sensory and behaviorally relevant variables, and these "mixed representations" are suggested to be important for perception, learning, and plasticity. However, the extent to which such integrative computations might occur in brain regions upstream of the forebrain is less clear.

Population coding of time-varying sounds in the non-lemniscal Inferior Colliculus.

The inferior colliculus (IC) of the midbrain is important for complex sound processing, such as discriminating conspecific vocalizations and human speech. The IC's non-lemniscal, dorsal "shell" region is likely important for this process, as neurons in these layers project to higher-order thalamic nuclei that subsequently funnel acoustic signals to the amygdala and non-primary auditory cortices; forebrain circuits important for vocalization coding in a variety of mammals, including humans. However, the extent to which shell IC neurons transmit acoustic features necessary to discern vocalizations is less clear, owing to the technical difficulty of recording from neurons in the IC's superficial layers via traditional approaches.

Recurrent Circuits Amplify Corticofugal Signals and Drive Feedforward Inhibition in the Inferior Colliculus.

The inferior colliculus (IC) is a midbrain hub critical for perceiving complex sounds, such as speech. In addition to processing ascending inputs from most auditory brainstem nuclei, the IC receives descending inputs from auditory cortex that control IC neuron feature selectivity, plasticity, and certain forms of perceptual learning. Although corticofugal synapses primarily release the excitatory transmitter glutamate, many physiology studies show that auditory cortical activity has a net inhibitory effect on IC neuron spiking.

Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression.

Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature.

Synaptic mechanisms of top-down control in the non-lemniscal inferior colliculus.

Corticofugal projections to evolutionarily ancient, subcortical structures are ubiquitous across mammalian sensory systems. These 'descending' pathways enable the neocortex to control ascending sensory representations in a predictive or feedback manner, but the underlying cellular mechanisms are poorly understood. Here, we combine optogenetic approaches with in vivo and in vitro patch-clamp electrophysiology to study the projection from mouse auditory cortex to the inferior colliculus (IC), a major descending auditory pathway that controls IC neuron feature selectivity, plasticity, and auditory perceptual learning.

Active dendritic integration and mixed neocortical network representations during an adaptive sensing behavior.

Animals strategically scan the environment to form an accurate perception of their surroundings. Here we investigated the neuronal representations that mediate this behavior. Ca imaging and selective optogenetic manipulation during an active sensing task reveals that layer 5 pyramidal neurons in the vibrissae cortex produce a diverse and distributed representation that is required for mice to adapt their whisking motor strategy to changing sensory cues.

Axonal Filtering Allows Reliable Output during Dendritic Plateau-Driven Complex Spiking in CA1 Neurons.

In CA1 pyramidal neurons, correlated inputs trigger dendritic plateau potentials that drive neuronal plasticity and firing rate modulation. Given the strong electrotonic coupling between soma and axon, the >25 mV depolarization associated with the plateau could propagate through the axon to influence action potential initiation, propagation, and neurotransmitter release. We examined this issue in brain slices, awake mice, and a computational model.

Inhibitory Gating of Input Comparison in the CA1 Microcircuit.

Spatial and temporal features of synaptic inputs engage integration mechanisms on multiple scales, including presynaptic release sites, postsynaptic dendrites, and networks of inhibitory interneurons. Here we investigate how these mechanisms cooperate to filter synaptic input in hippocampal area CA1. Dendritic recordings from CA1 pyramidal neurons reveal that proximal inputs from CA3 as well as distal inputs from entorhinal cortex layer III (ECIII) sum sublinearly or linearly at low firing rates due to feedforward inhibition, but sum supralinearly at high firing rates due to synaptic facilitation, producing a high-pass filter.

Control of interneuron firing by subthreshold synaptic potentials in principal cells of the dorsal cochlear nucleus.

Voltage-gated ion channels amplify, compartmentalize, and normalize synaptic signals received by neurons. We show that voltage-gated channels activated during subthreshold glutamatergic synaptic potentials in a principal cell generate an excitatory→inhibitory synaptic sequence that excites electrically coupled interneurons. In fusiform cells of the dorsal cochlear nucleus, excitatory synapses activate a TTX-sensitive Na(+) conductance and deactivate a resting Ih conductance, leading to a striking reshaping of the synaptic potential.

Superficial stellate cells of the dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) integrates auditory and multisensory signals at the earliest levels of auditory processing. Proposed roles for this region include sound localization in the vertical plane, head orientation to sounds of interest, and suppression of sensitivity to expected sounds. Auditory and non-auditory information streams to the DCN are refined by a remarkably complex array of inhibitory and excitatory interneurons, and the role of each cell type is gaining increasing attention.

Chemical synaptic transmission onto superficial stellate cells of the mouse dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) is a cerebellum-like auditory brain stem region whose functions include sound localization and multisensory integration. Although previous in vivo studies have shown that glycinergic and GABAergic inhibition regulate the activity of several DCN cell types in response to sensory stimuli, data regarding the synaptic inputs onto DCN inhibitory interneurons remain limited. Using acute DCN slices from mice, we examined the properties of excitatory and inhibitory synapses onto the superficial stellate cell, a poorly understood cell type that provides inhibition to DCN output neurons (fusiform cells) as well as to local inhibitory interneurons (cartwheel cells).

Regulation of interneuron excitability by gap junction coupling with principal cells.

Electrical coupling of inhibitory interneurons can synchronize activity across multiple neurons, thereby enhancing the reliability of inhibition onto principal cell targets. It is unclear whether downstream activity in principal cells controls the excitability of such inhibitory networks. Using paired patch-clamp recordings, we show that excitatory projection neurons (fusiform cells) and inhibitory stellate interneurons of the dorsal cochlear nucleus form an electrically coupled network through gap junctions containing connexin36 (Cxc36, also called Gjd2).

Rapid, activity-independent turnover of vesicular transmitter content at a mixed glycine/GABA synapse.

The release of neurotransmitter via the fusion of transmitter-filled, presynaptic vesicles is the primary means by which neurons relay information. However, little is known regarding the molecular mechanisms that supply neurotransmitter destined for vesicle filling, the endogenous transmitter concentrations inside presynaptic nerve terminals, or the dynamics of vesicle refilling after exocytosis. We addressed these issues by recording from synaptically coupled pairs of glycine/GABA coreleasing interneurons (cartwheel cells) of the mouse dorsal cochlear nucleus.

Multiple epidural lumbar chordomas without bone involvement in a 17-year-old female: a case report.

Background Context: Chordomas are rare slow-growing neoplasms or malignant tumors that arise from embryonic rudiments of the primitive notochord. They account for 1% to 4% of all primary malignant bone tumors. Surgery in addition to radiotherapy is often used as the optimum treatment but with marginal effectiveness as these tumors are relatively radioresistant.

Dendritic calcium channels and their activation by synaptic signals in auditory coincidence detector neurons.

The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca(2+).

Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development.

The development of glutamatergic synapses involves changes in the number and type of receptors present at the postsynaptic density. To elucidate molecular mechanisms underlying these changes, we combine in utero electroporation of constructs that alter the molecular composition of developing synapses with dual whole-cell electrophysiology to examine synaptic transmission during two distinct developmental stages. We find that SAP102 mediates synaptic trafficking of AMPA and NMDA receptors during synaptogenesis.

Lumbosacral junction fixation and fusion after complete L-5 spondylectomy. Case report.

The goals of surgery for metastatic disease of the lumbosacral spine are to relieve compression of the thecal sac and nerve roots, to resect malignant tissue, and to create a stable reconstruction of the spine. Reconstruction of the lumbosacral junction, specifically the L-5 vertebral body, is particularly challenging because the biomechanical properties of this level differ from other areas of the spine. A 40-year-old woman with intraductal breast carcinoma that metastasized to the L-5 vertebral body presented with progressive low-back pain, right-sided L-5 radiculopathy, and weakness.

Biomechanical analysis of multilevel cervical corpectomy and plate constructs.

Object: The authors compared the biomechanical stability of two multilevel cervical constructs involving the placement of equal size anterior cervical plates (ACPs) after decompressive surgery: the first is placed after three-level corpectomy with strut graft and the second after two-level corpectomy and aggressive discectomy with strut graft. In addition, both constructs were evaluated with and without the application of a screw attaching the ACP to the strut graft to determine whether the additional screw enhanced stability in any mode of loading.

Methods: Nondestructive repeated-measures in vitro flexibility tests were performed in human cadaveric cervical spines.