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Related Concept Videos

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Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
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Related Experiment Video

Updated: Aug 23, 2025

Morphological and Functional Evaluation of Ribbon Synapses at Specific Frequency Regions of the Mouse Cochlea
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Long-term microglia depletion impairs synapse elimination and auditory brainstem function.

Sima M Chokr1, Giedre Milinkeviciute1, Gisselle A Jimenez1

  • 1Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, 92697, USA.

Scientific Reports
|November 3, 2022
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Summary
This summary is machine-generated.

Microglia are essential immune cells for brain development. Sustained elimination of microglia impairs sound localization circuits, indicating their crucial role in repairing developmental deficits.

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Related Experiment Videos

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Area of Science:

  • Neuroscience
  • Immunology
  • Auditory System Development

Background:

  • Microglia, brain immune cells, regulate synaptic development and pruning essential for auditory circuit formation.
  • Previous studies showed postnatal inhibition of colony stimulating factor 1 receptor (CSF1R) with BLZ945 (BLZ) eliminates microglia, impairing calyceal pruning and auditory function.
  • Recovery of auditory function was observed upon microglia repopulation after BLZ cessation, but the necessity of this repopulation for repair remained unclear.

Purpose of the Study:

  • To investigate if auditory circuit deficits caused by microglial ablation can be repaired without microglia repopulation.
  • To examine the effects of sustained microglial elimination using a dual-drug approach (BLZ945 and PLX5622) on auditory development and function.

Main Methods:

  • Sustained microglial elimination was induced in mice using a combination of BLZ945 (BLZ) and PLX5622 (PLX).
  • Auditory brainstem responses (ABR) were measured to assess hearing thresholds, signal propagation, and other auditory parameters.
  • Histological analyses were performed to evaluate calyceal pruning, astrocyte maturation (GFAP expression), and glycine transporter 2 (GLYT2) levels in the medial nucleus of the trapezoid body (MNTB).

Main Results:

  • Sustained microglial elimination with BLZ/PLX resulted in impaired calyceal pruning and reduced astrocytic GFAP in the low-frequency MNTB region.
  • Elevated glycine transporter 2 (GLYT2) levels were observed in BLZ/PLX treated mice.
  • BLZ/PLX treatment led to elevated hearing thresholds, diminished peak amplitudes, and altered latencies in auditory brainstem responses.

Conclusions:

  • Sustained microglial elimination disrupts critical developmental processes in the auditory pathway, including calyceal pruning and astrocyte maturation.
  • The observed auditory deficits suggest that microglia are necessary for the proper development and function of sound localization circuits.
  • These findings underscore the essential role of microglia in repairing developmental deficits within the auditory system, highlighting that their return is likely required for functional recovery.