Deafness disrupts chloride transporter function and inhibitory synaptic transmission

Area of Science:

• Neuroscience
• Sensory Biology
• Cell Physiology

Background:

• Sensory deprivation in the developing central nervous system (CNS) can lead to neuronal atrophy or death.
• The physiological changes in remaining synapses after sensory loss are not well understood.

Purpose of the Study:

• To investigate the physiological changes in inhibitory synapses within the inferior colliculus following bilateral deafening.
• To determine the role of chloride transport mechanisms in synaptic function after hearing loss.

Main Methods:

• Gramicidin-perforated-patch recordings were performed on gerbil inferior colliculus neurons in brain slices.
• Electrophysiological techniques were used to assess inhibitory postsynaptic potentials (IPSPs) and action potential blocking.
• Semiquantitative RT-PCR and immunohistochemical staining were employed to analyze chloride cotransporter expression.

Main Results:

• Deafened neurons showed a reduced ability of evoked inhibitory postsynaptic potentials (IPSPs) to block action potentials.
• This deficit was linked to impaired potassium-dependent chloride transport, not altered K-Cl cotransporter expression.
• Pharmacological suppression of chloride cotransport affected control neurons but not deafened neurons, indicating a functional loss.

Conclusions:

• Profound hearing loss rapidly disrupts chloride homeostasis in the CNS.
• The dysfunction of the potassium-dependent chloride cotransport mechanism, rather than changes in its expression, underlies this disruption.
• Inhibitory synapses become less effective at controlling neuronal excitability after hearing loss.