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Sex-Specific Age-Related Changes in Excitatory and Inhibitory Intracortical Circuits in Mouse Primary Auditory

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Aging impairs hearing due to changes in the auditory cortex. Aged male mice show reduced connectivity in auditory circuits, suggesting sex-specific alterations contributing to hearing loss.

Keywords:
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Area of Science:

  • Neuroscience
  • Auditory Neuroscience
  • Aging Research

Background:

  • Age-related hearing loss (presbycusis) is a common impairment affecting spectrotemporal processing.
  • Dysfunctions in the peripheral and central auditory system contribute to presbycusis, with potential sex-specific differences.
  • Circuit mechanisms underlying age-related auditory dysfunction in the central nervous system are largely unknown.

Purpose of the Study:

  • To investigate age-related changes in auditory cortical microcircuits.
  • To determine if sex-dependent differences exist in these age-related changes.
  • To understand how alterations in inhibitory (GABA) and excitatory (NMDA, AMPA) neurotransmission impact auditory circuits.

Main Methods:

  • Laser-scanning photostimulation (LSPS) combined with whole-cell patch-clamp recordings.
  • Analysis of layer (L) 2/3 cells in the primary auditory cortex (A1).
  • Comparison between young adult (2-3 months) and aged (older than 18 months) male and female CBA/CaJ mice with normal peripheral hearing.

Main Results:

  • Aged male mice exhibited functional hypoconnectivity in inhibitory circuits originating from L2/3 and L4.
  • Excitatory connections from L2/3 were weaker in aged male mice compared to young adults.
  • An increased diversity of excitatory and inhibitory inputs was observed in aged male mice.

Conclusions:

  • Aging leads to sex-specific reductions and diversification in excitatory and inhibitory intralaminar cortical circuits.
  • These unbalanced circuit changes in aged mice may contribute to the functional manifestations of age-related hearing loss.
  • The findings highlight the importance of considering sex as a biological variable in aging auditory research.