Differences in developmental changes in GABAergic response between bushy and stellate cells in the rat anteroventral cochlear nucleus

Abstract

Many mammalian central nervous system neuron responses mediated by GABA(A) receptors undergo a developmental transition from excitation to inhibition, but little is known about the time of this switch in specific cell types in the developing anteroventral cochlear nucleus (AVCN). In the present study, bushy and stellate cells, two major cell types in the AVCN, were identified according to their morphology and electrophysiology. The equilibrium potential of GABA-evoked currents (E(GABA)) was examined using the gramicidin-perforated patch-clamp technique. We found that the action of GABA in bushy and stellate cells switched from predominantly depolarizing to predominantly hyperpolarizing with respect to their resting membrane potential (V(rest)) at different postnatal ages. Such a switch in the GABA response of bushy cells occurred before the first postnatal week, whereas that in stellate cells happened at the end of the second postnatal week. Furthermore, we discovered that bushy cells had a more depolarized V(rest) than did stellate cells before the second postnatal week; however, the E(GABA) of bushy and stellate cells was not significantly different. Thus, the discrepancy in the timing of the developmental shift from depolarizing to hyperpolarizing GABA responses between bushy and stellate cells may be due to the difference in their V(rest), but not due to E(GABA) itself. These results suggest that GABAergic inhibition functions earlier in bushy than in stellate cells. In contrast, the longer excitatory action of GABA on stellate cells possibly renders them more vulnerable than bushy cells to excitotoxic substances during early development.

Effects of bilirubin on the development and electrical activity of neural circuits

“…Therefore, GABA triggers Cl – efflux and leads to neuronal depolarization in immature neurons, which are high in [Cl – ]i, but mediates inhibition in mature neurons with low [Cl – ]i levels ( Ben-Ari et al, 2012 ). We also observed this shift in GABA function from excitatory to inhibitory in cochlear nucleus neurons ( Song et al, 2012 ). Notably, in the immature VCN neurons (P2–6), bilirubin dramatically increased the spontaneous firing rate, and blocking GABA/glycine receptors greatly attenuated the bilirubin-induced hyperexcitability ( Yin et al, 2016 ).…”

Postnatal development of synaptic properties of the GABAergic projection from the inferior colliculus to the auditory thalamus

“…The E GABA of MGB neurons at P8 (Ϫ57.9 Ϯ 3.3 mV) and P16 (Ϫ74.4 Ϯ 2.1 mV) with an extracellular Cl Ϫ concentration of 135 mM was comparable with the E GABA of rat cochlear nucleus cells from perforated-patch recordings when a similar extracellular Cl Ϫ concentration was used (Song et al 2012). The hyperpolarization of E GABA with age has been attributed to improved Cl Ϫ extrusion via KCC2.…”

Accelerated Development of the First-Order Central Auditory Neurons With Spontaneous Activity

“…On the basis of their distinct firing patterns in response to sustained depolarization, we broadly classified two groups of neurons, those that respond with a single spike only and those with a multiple spike response to a single current step. These single-spike and multi-spike firing patterns are well-established in mature CN neurons, resembling those of bushy cells and stellate cells at maturity (BCs and SCs), respectively (Oertel et al, 1990 ; Wang et al, 2010 ; Song et al, 2012 ). In slices from P4–P7 mice, we examined input-output relationships by first injecting a small hyperpolarization current (<50 pA) to arrest firings of IF(+) neurons and manually setting the same membrane potential (i.e., −60 mV) for both IF(+) and IF(−) neurons from their resting potentials (i.e., −50 to −55 mV) before delivering a series of current steps (−150 to +300 pA, 50 pA increments; Figure 7A,B ).…”