Hair Cell Mechanotransduction Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the Auditory System

Cell, Journal Year: 2018, Volume and Issue: 174(5), P. 1247 - 1263.e15

Published: Aug. 1, 2018

Language: Английский

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Transient cortical circuits match spontaneous and sensory-driven activity during development

Science, Journal Year: 2020, Volume and Issue: 370(6514)

Published: Oct. 16, 2020

At the earliest developmental stages, spontaneous activity synchronizes local and large-scale cortical networks. These networks form functional template for establishment of global thalamocortical architecture. The connections are established autonomously. However, from sensory periphery reshapes these circuits as soon afferents reach cortex. early-generated, largely transient neurons subplate play a key role in integrating sensory-driven activity. Early pathological conditions-such hypoxia, inflammation, or exposure to pharmacological compounds-alter patterns, which subsequently induce disturbances network This dysfunction may lead miswiring and, at later can be associated with neurological psychiatric conditions.

Language: Английский

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Prefrontal Cortex Development in Health and Disease: Lessons from Rodents and Humans

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 44(3), P. 227 - 240

Published: Nov. 24, 2020

The role of the prefrontal cortex (PFC) takes center stage among unanswered questions in modern neuroscience. PFC has a Janus-faced nature: it enables sophisticated cognitive and social abilities that reach their maximum expression humans, yet underlies some devastating symptoms psychiatric disorders. Accordingly, appropriate development is crucial for many high-order dysregulation this process been linked to various neuropsychiatric diseases. Reviewing recent advances field, with primary focus on rodents we highlight why, despite differences across species, cross-species approach fruitful strategy understanding development. We briefly review developmental contribution molecules extensively discuss how electrical activity controls early maturation wiring areas, as well emergence refinement input-output circuitry involved processing. Finally, mechanisms dysfunction relevance

Language: Английский

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Spontaneous activity in developing thalamic and cortical sensory networks

Neuron, Journal Year: 2021, Volume and Issue: 109(16), P. 2519 - 2534

Published: July 21, 2021

Language: Английский

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Deafness: from genetic architecture to gene therapy

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(10), P. 665 - 686

Published: May 12, 2023

Language: Английский

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Vesicular Glutamatergic Transmission in Noise-Induced Loss and Repair of Cochlear Ribbon Synapses

Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 39(23), P. 4434 - 4447

Published: March 29, 2019

Noise-induced excitotoxicity is thought to depend on glutamate. However, the excitotoxic mechanisms are unknown, and necessity of glutamate for synapse loss or regeneration unclear. Despite absence glutamatergic transmission from cochlear inner hair cells in mice lacking vesicular transporter-3 (Vglut3^KO), at 9–11 weeks, approximately half number synapses found Vglut3^WT were maintained as postsynaptic AMPA receptors juxtaposed with presynaptic ribbons voltage-gated calcium channels (Ca_V1.3). Synapses larger Vglut3^KO than Vglut3^WT. In Vglut3^+/− mice, 8–16 kHz octave-band noise exposure 100 dB sound pressure level caused a threshold shift (∼40 dB) (>50%) 24 h after exposure. Hearing partially recovered by 2 weeks became larger, whereas recovery was significantly better Noise 94 auditory shifts that fully suprathreshold hearing faster Vglut3^+/−. These results, both sexes, suggest spontaneous repair depends Vglut3 protein release during period. not observed Vglut3^KO, demonstrating its dependence release. Vglut3^+/−, unpairing Ca_V1.3, but where Ca_V1.3 remained clustered active zones. results that, without release, noise-induced Ca²⁺ influx insufficient disassemble zone. volume increased suggesting glutamate-independent mechanisms. SIGNIFICANCE STATEMENT mediated Vglut3, role Here, using we show one copy Vglut3 gene sufficient ribbon synapses, copies required normal function number. Impairment process having only functional suggests may promote regeneration. At least necessary loss. Although mechanism remains these findings consistent presumption key mediator synaptopathy.

Language: Английский

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Cellular and Widefield Imaging of Sound Frequency Organization in Primary and Higher Order Fields of the Mouse Auditory Cortex

Cerebral Cortex, Journal Year: 2019, Volume and Issue: 30(3), P. 1603 - 1622

Published: Aug. 28, 2019

Abstract The mouse auditory cortex (ACtx) contains two core fields—primary (A1) and anterior field (AAF)—arranged in a mirror reversal tonotopic gradient. best frequency (BF) organization naming scheme for additional higher order fields remain matter of debate, as does the correspondence between smoothly varying global tonotopy heterogeneity local cellular tuning. Here, we performed chronic widefield two-photon calcium imaging from ACtx awake Thy1-GCaMP6s reporter mice. Data-driven parcellation maps identified five fields, including previously unidentified area at ventral posterior extreme (VPAF) tonotopically organized suprarhinal (SRAF) that extended laterally far ectorhinal cortex. Widefield were stable over time, where single pixel BFs fluctuated by less than 0.5 octaves throughout 1-month period. After accounting neuropil signal tuning strength, BF neighboring layer 2/3 neurons was intermediate to heterogeneous salt pepper highly precise have each been described prior studies. Multiscale data suggest there is no ultrasonic or secondary mouse. Instead, VPAF dorsal (DP) emerged strongest candidates areas.

Language: Английский

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Shifting Developmental Trajectories During Critical Periods of Brain Formation

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Sept. 10, 2020

Research on critical periods of brain development is greatly expanding our understanding the cellular and molecular mechanisms underlying epochs heightened plasticity driven by environmental influence. Novel studies have started to reveal that timely interventions during hold potential reorient abnormal developmental trajectories in animal models neurological neuropsychiatric disorders. In this review, we re-examine fundamental criteria characterize a period, highlighting recently discovered health disease. addition, touch upon technological improvements modelling human-derived neural networks vitro. These scientific advances associated with use manipulations immature represent promising new preclinical setting will allow future translatability into clinical applications for neurodevelopmental disorders such as intellectual disability, autism spectrum schizophrenia.

Language: Английский

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The Neural Bases of Tinnitus: Lessons from Deafness and Cochlear Implants

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(38), P. 7190 - 7202

Published: Sept. 16, 2020

Subjective tinnitus is the conscious perception of sound in absence any acoustic source. The literature suggests various mechanisms, most which invoke changes spontaneous firing rates central auditory neurons resulting from modification neural gain. Here, we present an alternative model based on evidence that is: (1) rare people who are congenitally deaf, (2) common with acquired deafness, and (3) potentially suppressed by active cochlear implants used for hearing restoration. We propose can only develop after fast fiber activity has stimulated synapse formation between fast-spiking parvalbumin positive (PV⁺) interneurons projecting ascending path coactivated frontostriatal networks onset. Thereafter, promotes feedforward feedback inhibition mediated PV⁺ interneuron auditory-specific circuits. This inhibitory network enables enhanced stimulus resolution, attention-driven contrast improvement, augmentation responses pathways (neural gain) damage slow fibers. When lost, tonic diminished, prolonged response latencies, sudden hyperexcitability, cortical synchrony, elevated γ oscillations, impaired attention/stress-control have been described previous models. Moreover, because processing gained through sensory experience, would not exist congenital deafness. Electrical stimulation may potential to reestablish thus suppress tinnitus. proposed framework unites many ideas pathophysiology catalyze cooperative efforts therapies.

Language: Английский

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How development sculpts hippocampal circuits and function

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(1), P. 343 - 378

Published: July 19, 2021

In mammals, the selective transformation of transient experience into stored memory occurs in hippocampus, which develops representations specific events context they occur. this review, we focus on development hippocampal circuits and self-organized dynamics embedded within them since latter critically support role hippocampus learning memory. We first discuss evidence that adult cells are sculpted by as early during embryonic neurogenesis. argue these primary developmental programs provide a scaffold onto later external world can be grafted. Next, review different sequences at anatomical functional levels. cover period extending from neurogenesis migration to appearance phenotypic diversity their wiring networks. describe progressive emergence network sensorimotor-driven sharp waves place tracking relational information. outline critical turn points discontinuities journey, close formulating open questions. propose rewinding process helps understand main organization principles circuits.

Language: Английский

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