Dataset Information

Impact of Auditory Experience on the Structural Plasticity of the AIS in the Mouse Brainstem Throughout the Lifespan.

ABSTRACT: Sound input critically influences the development and maintenance of neuronal circuits in the mammalian brain throughout life. We investigate the structural and functional plasticity of auditory neurons in response to various auditory experiences during development, adulthood, and aging. Using electrophysiology, computer simulation, and immunohistochemistry, we study the structural plasticity of the axon initial segment (AIS) in the medial nucleus of the trapezoid body (MNTB) from the auditory brainstem of the mice (either sex), in different ages and auditory environments. The structure and spatial location of the AIS of MNTB neurons depend on their functional topographic location along the tonotopic axis, aligning high- to low-frequency sound-responding neurons (HF or LF neurons). HF neurons dramatically undergo structural remodeling of the AIS throughout life. The AIS progressively shortens during development, is stabilized in adulthood, and becomes longer in aging. Sound inputs are critically associated with setting and maintaining AIS plasticity and tonotopy at various ages. Sound stimulation increases the excitability of auditory neurons. Computer simulation shows that modification of the AIS length, location, and diameter can affect firing properties of MNTB neurons in the developing brainstem. The adaptive capability of axonal structure in response to various auditory experiences at different ages suggests that sound input is important for the development and maintenance of the structural and functional properties of the auditory brain throughout life.

SUBMITTER: Kim EJ

PROVIDER: S-EPMC6813928 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Impact of Auditory Experience on the Structural Plasticity of the AIS in the Mouse Brainstem Throughout the Lifespan.

Kim Eun Jung EJ Feng Chenling C Santamaria Fidel F Kim Jun Hee JH

Frontiers in cellular neuroscience 20191015

Sound input critically influences the development and maintenance of neuronal circuits in the mammalian brain throughout life. We investigate the structural and functional plasticity of auditory neurons in response to various auditory experiences during development, adulthood, and aging. Using electrophysiology, computer simulation, and immunohistochemistry, we study the structural plasticity of the axon initial segment (AIS) in the medial nucleus of the trapezoid body (MNTB) from the auditory b ...[more]

PMID: 31680869

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Project description:BackgroundChronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression. While it is clear that chronic microglial inflammation and enhanced ROS production impact neuronal integrity, little is known about how acute microglial inflammation influences AIS stability. Here, we demonstrate that acute neuroinflammation induces AIS structural plasticity in a ROS-mediated and calpain-dependent manner.MethodsC57BL/6J and NOX2-/- mice were given a single injection of lipopolysaccharide (LPS; 5 mg/kg) or vehicle (0.9% saline, 10 mL/kg) and analyzed at 6 h-2 weeks post-injection. Anti-inflammatory Didox (250 mg/kg) or vehicle (0.9% saline, 10 mL/kg) was administered beginning 24 h post-LPS injection and continued for 5 days; animals were analyzed 1 week post-injection. Microglial inflammation was assessed using immunohistochemistry (IHC) and RT-qPCR, and AIS integrity was quantitatively analyzed using ankyrinG immunolabeling. Data were statistically compared by one-way or two-way ANOVA where mean differences were significant as assessed using Tukey's post hoc analysis.ResultsLPS-induced neuroinflammation, characterized by enhanced microglial inflammation and increased expression of ROS-producing enzymes, altered AIS protein clustering. Importantly, inflammation-induced AIS changes were reversed following resolution of microglial inflammation. Modulation of the inflammatory response using anti-inflammatory Didox, even after significant AIS disruption occurred, increased the rate of AIS recovery. qPCR and IHC analysis revealed that expression of microglial NOX2, a ROS-producing enzyme, was significantly increased correlating with AIS disruption. Furthermore, ablation of NOX2 prevented inflammation-induced AIS plasticity, suggesting that ROS drive AIS structural plasticity.ConclusionsIn the presence of acute microglial inflammation, the AIS undergoes an adaptive change that is capable of spontaneous recovery. Moreover, recovery can be therapeutically accelerated. Together, these findings underscore the dynamic capabilities of this domain in the presence of a pathological insult and provide evidence that the AIS is a viable therapeutic target.

Dataset Information

Impact of Auditory Experience on the Structural Plasticity of the AIS in the Mouse Brainstem Throughout the Lifespan.

Publications

Impact of Auditory Experience on the Structural Plasticity of the AIS in the Mouse Brainstem Throughout the Lifespan.

Similar Datasets

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