Naturally occurring neuron death during postnatal development of the gerbil ventral cochlear nucleus begins at the onset of hearing

Short-term changes in synaptic gain support information processing throughout the CNS, yet we know little about the developmental regulation of such plasticity. Here we report that auditory experience is necessary for the normal maturation of synaptic inhibitory short-term plasticity (iSTP) in the auditory cortex, and that presynaptic GABA B receptors regulate this development. Moderate or severe hearing loss was induced in gerbils, and iSTP was characterized by measuring inhibitory synaptic current amplitudes in response to repetitive stimuli. We reveal a profound developmental shift of iSTP from depressing to facilitating after the onset of hearing. Even moderate hearing loss prevented this shift. This iSTP change was mediated by a specific class of inhibitory interneurons, the lowthreshold spiking cells. Further, using paired recordings, we reveal that presynaptic GABA B receptors at interneuron-pyramidal connections regulate iSTP in an experience-dependent manner. This novel synaptic mechanism may support the emergence of mature temporal processing in the auditory cortex.

Section: Methodsmentioning

confidence: 99%

Presynaptic GABA_BReceptors Regulate Experience-Dependent Development of Inhibitory Short-Term Plasticity

Takesian¹,

Kotak²,

Sanes³

2010

“…Thus, the recordings were not performed blind. The age of surgery was chosen based on the work of Tierney and Moore (1997) showing that anteroventral cochlear nucleus cell number is unaffected by cochlear ablation at P9. Thalamocortical brain slice recordings and pharmacology.…”

Section: Methodsmentioning

confidence: 99%

Hearing Loss Raises Excitability in the Auditory Cortex

Kotak¹,

Fujisawa²,

Lee³

et al. 2005

262

243

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.

“…Thus, the recordings were not performed blind. The age of surgery was chosen based on the finding that anteroventral cochlear nucleus cell number is unaffected by cochlear ablation after P9 in gerbils (Tierney and Moore, 1997). In addition, sham surgery was performed on six animals at P10.…”

Section: Methodsmentioning

confidence: 99%

Conductive Hearing Loss Disrupts Synaptic and Spike Adaptation in Developing Auditory Cortex

Han¹,

Kotak²,

Sanes³

2007

102

Although sensorineural hearing loss (SNHL) is known to compromise central auditory structure and function, the impact of milder forms of hearing loss on cellular neurophysiology remains mostly undefined. We induced conductive hearing loss (CHL) in developing gerbils, reared the animals for 8 -13 d, and subsequently assessed the temporal features of auditory cortex layer 2/3 pyramidal neurons in a thalamocortical brain slice preparation with whole-cell recordings. Repetitive stimulation of the ventral medial geniculate nucleus (MGv) evoked robust short-term depression of the postsynaptic potentials in control neurons, and this depression increased monotonically at higher stimulation frequencies. In contrast, CHL neurons displayed a faster rate of synaptic depression and a smaller asymptotic amplitude. Moreover, the latency of MGv evoked potentials was consistently longer in CHL neurons for all stimulus rates. A separate assessment of spike frequency adaptation in response to trains of injected current pulses revealed that CHL neurons displayed less adaptation compared with controls, although there was an increase in temporal jitter. For each of these properties, nearly identical findings were observed for SNHL neurons. Together, these data show that CHL significantly alters the temporal properties of auditory cortex synapses and spikes, and this may contribute to processing deficits that attend mild to moderate hearing loss.