期刊
JOURNAL OF NEUROSCIENCE
卷 25, 期 15, 页码 3908-3918出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5169-04.2005
关键词
homeostasis; synaptic plasticity; GABA(A); NMDA receptor; mEPSC; disuse
资金
- NEI NIH HHS [EY 13145, R01 EY013145] Funding Source: Medline
- NIDCD NIH HHS [DC00540, DC006864, R01 DC006864, R01 DC000540] Funding Source: Medline
- NINDS NIH HHS [R01 NS041091, NS041091] Funding Source: Medline
Developmental hearing impairments compromise sound discrimination, speech acquisition, and cognitive function; however, the adjustments of functional properties in the primary auditory cortex (A1) remain unknown. We induced sensorineural hearing loss (SNHL) in developing gerbils and then reared the animals for several days. The intrinsic membrane and synaptic properties of layer 2/3 pyramidal neurons were subsequently examined in a thalamocortical brain slice preparation with whole-cell recordings and electron microscopic immunocytochemistry. SNHL neurons displayed a depolarized resting membrane potential, an increased input resistance, and a higher incidence of sustained firing. They also exhibited significantly larger thalamocortically and intracortically evoked excitatory synaptic responses, including a greater susceptibility to the NMDA receptor antagonist AP-5 and the NR2B subunit antagonist ifenprodil. This correlated with an increase in NR2B labeling of asymmetric synapses, as visualized ultrastructurally. Furthermore, decreased frequency and increased amplitude of miniature EPSCs (mEPSCs) in SNHL neurons suggest that a decline in presynaptic release properties is compensated by an increased excitatory response. To verify that the increased thalamocortical excitation was elicited by putative monosynaptic connections, minimum amplitude ventral medial geniculate nucleus-evoked EPSCs were recorded. These minimum-evoked responses were of larger amplitude, and the NMDAergic currents were also larger and longer in SNHL neurons. These findings were supported by significantly longer AP-5-sensitive durations and larger amplitudes of mEPSCs. Last, the amplitudes of intracortically evoked monosynaptic and polysynaptic GABAergic inhibitory synaptic responses were significantly smaller in SNHL neurons. These alterations in cellular properties after deafness reflect an attempt by A1 to sustain an operative level of cortical excitability that may involve homeostatic mechanisms.
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