Heterogeneous Kinetics and Pharmacology of Synaptic Inhibition in the Chick Auditory Brainstem

Abstract

Identification of shared features between avian and mammalian auditory brainstem circuits has provided much insight into the mechanisms underlying early auditory processing. However, previous studies have highlighted an apparent difference in inhibitory systems; synaptic inhibition is thought to be slow and GABAergic in birds, but to have fast kinetics and be predominantly glycinergic in mammals. Using patch-clamp recordings in chick brainstem slices, we found this distinction is not exclusively true. Consistent with previous work, inhibitory postsynaptic currents (IPSCs) in nucleus magnocellularis (NM) were slow and mediated by GABAA receptors. However, IPSCs in nucleus laminaris (NL) and a subset of neurons in nucleus angularis (NA) had rapid time courses two to three-fold faster than those in NM. Further, we found IPSCs in NA were mediated by both glycine and GABAA receptors, demonstrating for the first time a role for fast glycinergic transmission in the avian auditory brainstem. Although NM, NL and NA have unique roles in auditory processing, the majority of inhibitory input to each nucleus arises from the same source, ipsilateral superior olivary nucleus (SON). Our results demonstrate remarkable diversity of inhibitory transmission among the avian brainstem nuclei and suggest differential glycine and GABAA receptor activity tailors inhibition to the specific functional roles of NM, NL, and NA despite common SON input. We additionally observed that glycinergic/GABAergic activity in NA was usually depolarizing and could elicit spiking activity in NA neurons. Because NA projects to SON, these excitatory effects may influence the recruitment of inhibitory activity in the brainstem nuclei.

GABAergic and glycinergic inhibition modulate monaural auditory response properties in the avian superior olivary nucleus

“…Double exponential fits were chosen if the sum of the squared errors was less than half that of the single exponential fit. A weighted decay value was calculated for double exponential fits using the equation: Kuo et al (2009). sIPSC frequency (Hz) was also calculated.…”

“…To anatomically confirm GABA and glycine neurotransmitter at terminals, immunohistochemistry following the protocol of Kuo et al (2009) was performed. Briefly, three mature chickens ranging in age from P17-P23 were deeply anesthetized as previously described and transcardially perfused with PBS then 2% PFA and 2% glutaraldehyde (Grade 1; Sigma) in PBS, pH 7.4.…”

“…These studies suggested that GABAergic inhibition at NL and NM arising from the SON has relatively slow kinetic properties and is unlikely to contribute to temporal properties on a cycle-by-cycle basis. More recent work has shown that inhibitory signaling within the avian auditory brainstem is not solely GABAergic but also includes a glycinergic component endowed with faster kinetics (Kuo et al 2009). The source of this glycinergic input is unknown but appears to derive from corelease of GABA and glycine from some inhibitory terminals (Kuo et al 2009).…”

Heterogeneous Calretinin Expression in the Avian Cochlear Nucleus Angularis

“…Using Golgi labeling methods and intracellular fills that allow dendritic ramifications to be observed, four different cell types have been identified in NA on morphological grounds in multiple avian species: planar, large radiate, vertical, and stubby (pigeon: Häusler et al 1999;chick: Soares et al 2002; barn owl: Soares and Carr 2001; emu: MacLeod, Soares, and Carr personal observations). In vitro physiological response types have been defined in the chick and include several varieties of repetitive-spiking cell types and a phasic, "single spiking" response types, the latter of which resembled neurons in the timing pathways Fukui and Ohmori 2003;Kuo et al 2009;Soares et al 2002); these intrinsic properties may have important implications for both level and spectrotemporal processing in NA (Kreeger et al 2012). Physiological responses types in vivo corresponded closely to those found in the mammal ventral cochlear nucleus, including "primarylike" (resembling phasic-tonic nerve discharges), "chopper" (characterized by intrinsic repetitive spiking and poor phase-locking to the carrier wave), and "onset" types (Hotta 1971; Köppl and Carr 2003;Sachs and Sinnott 1978;Warchol and Dallos 1990; see also Köppl and Carr (2003) for a discussion of these response types in the avian system).…”

The Impact of Child Sexual Abuse

“…Women that did not experience CSA were automatically assigned a zero value for each dimension of a CSA experience. Among women reporting multiple non-overlapping abuse incidents occurring each time with a different perpetrator(s), we derived a cumulative score of CSA severity by summing each multidimensional index corresponding to the separate incidents (15).…”