Differential Inhibitory Control of Semicircular Canal Nerve Afferent-Evoked Inputs in Second-Order Vestibular Neurons by Glycinergic and GABAergic Circuits

Abstract

Labyrinthine nerve-evoked monosynaptic excitatory postsynaptic potentials (EPSPs) in second-order vestibular neurons (2 degrees VN) sum with disynaptic inhibitory postsynaptic potentials (IPSPs) that originate from the thickest afferent fibers of the same nerve branch and are mediated by neurons in the ipsilateral vestibular nucleus. Pharmacological properties of the inhibition and the interaction with the afferent excitation were studied by recording monosynaptic responses of phasic and tonic 2 degrees VN in an isolated frog brain after electrical stimulation of individual semicircular canal nerves. Specific transmitter antagonists revealed glycine and GABA(A) receptor-mediated IPSPs with a disynaptic onset only in phasic but not in tonic 2 degrees VN. Compared with GABAergic IPSPs, glycinergic responses in phasic 2 degrees VN have larger amplitudes and a longer duration and reduce early and late components of the afferent nerve-evoked subthreshold activation and spike discharge. The difference in profile of the disynaptic glycinergic and GABAergic inhibition is compatible with the larger number of glycinergic as opposed to GABAergic terminal-like structures on 2 degrees VN. The increase in monosynaptic excitation after a block of the disynaptic inhibition in phasic 2 degrees VN is in part mediated by a N-methyl-d-aspartate receptor-activated component. Although inhibitory inputs were superimposed on monosynaptic EPSPs in tonic 2 degrees VN as well, the much longer latency of these IPSPs excludes a control by short-latency inhibitory feed-forward side-loops as observed in phasic 2 degrees VN. The differential synaptic organization of the inhibitory control of labyrinthine afferent signals in phasic and tonic 2 degrees VN is consistent with the different intrinsic signal processing modes of the two neuronal types and suggests a co-adaptation of intrinsic membrane properties and emerging network properties.

Differential Dynamic Processing of Afferent Signals in Frog Tonic and Phasic Second-Order Vestibular Neurons

“…The different impedance behavior during membrane polarization makes the two subtypes most suitable for amplification (tonic 2°VNs) and differentiation (phasic 2°VNs) of vestibular inputs (Beraneck et al, 2007). A different insertion of the two neuronal subtypes into local inhib-itory networks as indicated by the presence of ipsilateral disynaptic feedforward IPSPs in phasic but not tonic 2°VNs (Biesdorf et al, 2008) concurs with the highly transient intrinsic properties of the former neurons. The distinctly different filter properties and their differential effect on single monosynaptic afferent EPSPs in phasic and tonic 2°VNs suggests that more complex synaptic inputs similar to those that occur during natural head movements would be the appropriate test to reveal the different modes of signal processing of the two subtypes.…”

“…Two different parameter sets for synaptic innervation were used: the "E compartmental model" consisted of one excitatory synapse at the last dendritic compartment with the following parameters: 1 ϭ 5 ms, 2 ϭ 97 ms, g sE ϭ 16.8 nS. To mimic the monosynaptic excitation, a delay of 3.4 ms (Biesdorf et al, 2008) from the stimulus to the onset of the excitation was used. For the "E/I compartmental model" the E compartmental model was extended by two inhibitory synapses at the soma: glycine ( 1 ϭ 2 ms, 2 ϭ 200 ms, g sI ϭ 22.5 nS) and GABA A ( 1 ϭ 2 ms, 2 ϭ 91 ms, g sI ϭ 16.8 nS).…”

“…For the "E/I compartmental model" the E compartmental model was extended by two inhibitory synapses at the soma: glycine ( 1 ϭ 2 ms, 2 ϭ 200 ms, g sI ϭ 22.5 nS) and GABA A ( 1 ϭ 2 ms, 2 ϭ 91 ms, g sI ϭ 16.8 nS). All synaptic time constants and conductances were obtained by fitting published experimental data (Biesdorf et al, 2008). The inhibition for the stimulation paradigms 70 Hz/2.5 s (peak frequency/half-cycle length) in the model was activated by detected spike events of phasic or tonic neurons, using a synaptic delay of 1.8 ms (Straka et al 1997).…”

“…The early truncation of the compound responses and the marked reduction of single EPSP amplitudes that likely contributes to the peak advance in phasic 2°VNs might not only be caused by prominent voltage-dependent potassium conductances (Beraneck et al, 2007), but also by inhibitory synaptic inputs superimposed on the afferent-evoked monosynaptic excitation (Biesdorf et al, 2008). A potential contribution of glycinergic and GABAergic IPSPs to the nonlinear characteristics of compound responses in phasic 2°VNs was studied by bath application of the respective transmitter antagonists (Fig.…”

“…6 D, asterisk), it suggests that at least part of the observed shunting during the stimulus train was caused by inhibitory inputs. Probable neuronal candidates for mediating the glycinergic and GABAergic inhibition are ipsilateral vestibular inhibitory interneurons (Straka and Dieringer, 1996) that have been shown to activate disynaptic IPSPs in phasic, but not in tonic 2°VNs after electrical stimulation of vestibular nerve afferent fibers (Biesdorf et al, 2008). An ipsilateral origin was confirmed by the recordings of several phasic 2°VNs (n ϭ 6) in isolated frog brains in which the midline was completely transected from the optic tectum to the obex.…”