Development of glycinergic and glutamatergic synaptic transmission in the auditory brainstem of perinatal rats

Abstract

In contrast to our knowledge about the anatomical development of the mammalian central auditory system, the development of its physiological properties is still poorly understood. In order to better understand the physiological properties of the developing mammalian auditory brainstem, we made intracellular recordings in brainstem slices from perinatal rats to examine synaptic transmission in the superior olivary complex, the first binaural station in the ascending auditory pathway. We concentrated on neurons in the lateral superior olive (LSO), which in adults, are excited from the ipsilateral side and inhibited from the contralateral side. Already at embryonic day (E) 18, when axon collaterals begin to invade the LSO anlage, synaptic potentials could be evoked from ipsilateral, as well as from contralateral inputs. Ipsilaterally elicited PSPs were always depolarizing, regardless of age. They had a positive reversal potential and could be completely blocked by the non-NMDA glutamate receptor antagonist CNQX. In contrast, contralaterally elicited PSPs were depolarizing from E18-P4, yet they turned into "adult-like," hyperpolarizing PSPs after P8. Their reversal potential shifted dramatically from -21.6 +/- 17.7 mV (E18-P0) to -73.0 +/- 7.1 mV (P10). Regardless of their polarity, contralaterally elicited PSPs were reversibly blocked by the glycine receptor antagonist strychnine. Bath application of glycine and its agonist beta-alanine further confirmed the transitory depolarizing action of glycine in the auditory brainstem. Since the transient excitatory behavior of glycine occurs during a period during which glycinergic synaptic connections in the LSO are refined by activity-dependent mechanisms, glycinergic excitation might be a mechanism by which synaptic rearrangement in the contralateral inhibitory pathway is accomplished.

Glycinergic/GABAergic synapses in the lateral superior olive are excitatory in neonatal C57Bl/6J mice

“…These PSPs had onset latencies of 5.5±0.8 ms (n = 6) in P1-P2 mice and 5.0±0.5 ms (n = 13) in P4-P7 mice. These values are comparable to those reported for newborn rats [11] and gerbils [15] and about 3 ms longer than the latencies reported for 3-week-old mice [17]. In slices prepared from P1 and P2 mice MNTB-evoked PSPs (recorded in perforatedpatch mode) were always depolarizing from the resting membrane potential (n = 8, V rest −51.8 ± 1.4 mV) (Fig.…”

“…These data indicate that MNTB-evoked PSPs are primarily depolarizing up to P3 and hyperpolarizing thereafter. Thus, compared to rats [11] or gerbils [12] MNTB-evoked PSPs in mice become hyperpolarizing 5-7 days earlier, consistent with the somewhat faster maturation of the mouse auditory system [5].…”

“…These data indicate that MNTB-evoked PSPs are primarily depolarizing up to P3 and hyperpolarizing thereafter. Thus, compared to rats [11] or gerbils [12] MNTB-evoked PSPs in mice become hyperpolarizing 5-7 days earlier, consistent with the somewhat faster maturation of the mouse auditory system [5].Recently, it has been demonstrated that glycine can elicit action potentials (APs) in immature rat LSO neurons [7] suggesting that glycine can act as an excitatory neurotransmitter in the LSO. However, in these studies glycine was applied iontophoretically to the cell body, a somewhat artificial situation because it activates both synaptic, as well as extrasynaptic, glycine receptors.…”

“…During early postnatal development, the spatial connectivity pattern of this inhibitory MNTB-LSO pathway is sharpened by activity-dependent mechanisms resulting in the precise tonotopic organization seen in adult animals (for review see [15,16]). During the first postnatal week, glycinergic/GABAergic MNTB-LSO synapses are not hyperpolarizing as in adult animals, but are depolarizing due to a high internal chloride concentration of LSO neurons [7,11]. It has been suggested that this depolarization renders the MNTB pathway excitatory and that the excitatory nature is part of the mechanism by which activity in the MNTB-LSO pathways exerts its effect on neuronal growth, survival, and synaptic In the present study, we examined whether and at what age the MNTB-LSO pathway is depolarizing and whether it can elicit action potentials in LSO neurons of mice.…”

Reciprocal developmental regulation of presynaptic ionotropic receptors

“…Other studies have described several major changes in inhibitory transmission in nuclei of the superior olivary complex. In the lateral superior olive, inhibitory transmission shifts from depolarizing to hyperpolarizing in the first week after birth (11,12). Moreover, IPSCs generated by MNTB neurons in the lateral superior olive and the medial superior olive initially are mediated in part by GABA and, later, become exclusively glycinergic in the 2 weeks after birth (11,13).…”