Inhibitory projections from the ventral nucleus of the trapezoid body to the medial nucleus of the trapezoid body in the mouse

Abstract

Neurons in the medial nucleus of the trapezoid body (MNTB) receive prominent excitatory input through the calyx of Held, a giant synapse that produces large and fast excitatory currents. MNTB neurons also receive inhibitory glycinergic inputs that are also large and fast, and match the calyceal excitation in terms of synaptic strength. GABAergic inputs provide additional inhibition to MNTB neurons. Inhibitory inputs to MNTB modify spiking of MNTB neurons both in-vitro and in-vivo, underscoring their importance. Surprisingly, the origin of the inhibitory inputs to MNTB has not been shown conclusively. We performed retrograde tracing, anterograde tracing, immunohistochemical experiments, and electrophysiological recordings to address this question. The results support the ventral nucleus of the trapezoid body (VNTB) as at least one major source of glycinergic input to MNTB. VNTB fibers enter the ipsilateral MNTB, travel along MNTB principal neurons and produce several bouton-like presynaptic terminals. Further, the contribution of GABA to the total inhibition declines during development, resulting in only a very minor fraction of GABAergic inhibition in adulthood, which is matched in time by a reduction in expression of a GABA synthetic enzyme in VNTB principal neurons.

Glycinergic inhibition to the medial nucleus of the trapezoid body shows prominent facilitation and can sustain high levels of ongoing activity

“…The excitatory input to MNTB originates from globular bushy cells in the contralateral ventral cochlear nucleus (Held 1892(Held , 1893Tolbert et al 1982). One major source of inhibitory inputs to MNTB is the ipsilateral VNTB (Albrecht et al 2014;Thompson and Schofield 2000), which in turn receives excitatory input from globular bushy and/or stellate cells in the contralateral cochlear nucleus Thompson 1998;Warr 1969). Thus both inputs to MNTB originate, directly or indirectly, in the contralateral cochlear nucleus, are of auditory nature, respond to sound stimulation with ongoing firing patterns, have relatively high activity levels, and are very likely characterized by spontaneous activity.…”

“…Recent work suggested that the main source of inhibition to MNTB may originate from the VNTB (Albrecht et al 2014). VNTB neurons, like the majority of auditory brain stem neurons, receive inputs that are highly active during the presentation of sound and additionally are spontaneously active during acoustic silence.…”

“…Several anatomical sources for inhibition to MNTB neurons have been suggested (Albrecht et al 2014;Smith et al 1998;Thompson and Schofield 2000). To assess the sum of inhibitory inputs independent of their source(s), we chose to stimulate inhibitory inputs in the direct vicinity of the MNTB neuron from which we recorded (Fig.…”

“…Although intrinsic projections within MNTB have been suggested as one possible source of inhibitory inputs (Kuwabara and Zook 1991), a recent study has shown that the ipsilateral ventral nucleus of the trapezoid body (VNTB) is their main extrinsic source (Albrecht et al 2014). VNTB neurons receive excitatory input from stellate cells in the contralateral cochlear nucleus (Thompson 1998;Warr 1969) with tonic/chopping firing patterns (Oertel 2011) and/or excitatory input from globular bushy cells in the contralateral cochlear nucleus Spirou et al 1990) with primary-like or primary-like with notch firing patterns (Smith et al 1991).…”

“…Moreover, MNTB neurons themselves receive synaptic inhibition (Albrecht et al 2014;Awatramani et al 2004;Green and Sanes 2005;Smith et al 1998;Thompson and Schofield 2000), which modifies firing patterns of MNTB neurons (Green and Sanes 2005; KoppScheinpflug et al 2008;Tolnai et al 2008).…”