Excitatory–Inhibitory Synaptic Coupling in Avian Nucleus Magnocellularis

Abstract

The activity of neurons is determined by the balance between their excitatory and inhibitory synaptic inputs. Neurons in the avian nucleus magnocellularis (NM) integrate monosynaptic excitatory and polysynaptic inhibitory inputs from the auditory nerve, and transmit phase-locked output to higher auditory centers. The excitatory input is graded tonotopically, such that neurons tuned to higher frequency receive fewer, but larger, axon terminals. However, it remains unknown how the balance between excitatory and inhibitory inputs is determined in NM. We here examined synaptic and spike responses of NM neurons during stimulation of the auditory nerve in thick brain slices of chicken of both sexes, and found that the excitatory-inhibitory balance varied according to tonotopic region, ensuring reliable spike output across frequencies. Auditory nerve stimulation elicited IPSCs in NM neurons regardless of tonotopic region, but the dependence of IPSCs on intensity varied in a systematic way. In neurons tuned to low frequency, IPSCs appeared and increased in parallel with EPSCs with elevation of intensity, which expanded dynamic range by preventing saturation of spike generation. On the other hand, in neurons tuned to higher frequency, IPSCs were smaller than EPSCs and had higher thresholds for activation, thus facilitating highfidelity transmission. Computer simulation confirmed that these differences in inhibitory input were optimally matched to the patterns of excitatory input, and enabled appropriate level of neuronal output for wide intensity and frequency ranges of sound in the auditory system.

Tonotopic Specializations in Number, Size, and Reversal Potential of GABAergic Inputs Fine-Tune Temporal Coding at Avian Cochlear Nucleus

“…Tonotopic regions of NM. Definitions of tonotopic regions were described previously (Al-Yaari et al, 2020), and neurons in low-CF and high-CF regions were used in this study. The low-CF region would correspond to NMc in Wang et al (2017), where neurons have substantial dendrites (Akter et al, 2018).…”

“…Slice preparation. Slices were prepared as described previously (Al-Yaari et al, 2020). After decapitation under deep anesthesia with ether, brainstem was isolated and immersed in an oxygenated ice-cold highglucose ACSF (HG-ACSF, concentration in mM as follows: 75 NaCl, 2.5 KCl, 26 NaHCO 3 , 1.25 NaH 2 PO 4 , 1 CaCl 2 , 3 MgCl 2 , 100 glucose, saturated with 95% O 2 and 5% CO 2 ).…”

“…Biphasic square pulses were produced with an electronic stimulator (SEN-7203, Nihon Kohden) and applied through an isolator (SS-202J, Nihon Kohden). Stimulus intensity was adjusted by changing the duration of pulses at a constant amplitude (Al-Yaari et al, 2020).…”

“…1A) (Lachica et al, 1994;Yang et al, 1999;Burger et al, 2005). Recently, we showed that GABAergic inputs increase linearly with excitatory inputs in low-CF neurons during the auditory nerve stimulation, whereas they are recruited at much higher intensities than excitatory inputs in high-CF neurons (Al-Yaari et al, 2020). The linearly coupled GABAergic inputs in the low-CF neurons would require fine adjustment of synaptic conductance, including the size as well as the number of unitary conductance.…”

Structural and Functional Refinement of the Axon Initial Segment in Avian Cochlear Nucleus during Development

“…As in other auditory nuclei, NM is organized tonotopically, in a way that the characteristic frequency (CF) of neurons decreases from rostromedial to caudolateral direction (Rubel and Parks, 1975). NM neurons show different properties along this tonotopic axis (Fukui and Ohmori, 2004;Oline et al, 2016;Wang et al, 2017;Al-Yaari et al, 2020). In particular, the AIS is shorter and accumulates fewer Na v channels at the higher-CF region (Kuba and Ohmori, 2009).…”