Developmental Profiles of the Intrinsic Properties and Synaptic Function of Auditory Neurons in Preterm and Term Baboon Neonates

Abstract

The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABA A /glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse.

Yes, there is a medial nucleus of the trapezoid body in humans

“…This principle states that, in consideration of historical homology, the explanation that requires the fewest assumptions and phylogenic transformations is most likely to be correct. As the MNTB has been demonstrated (without question) to exist in other primates (rhesus, baboon, bonobo, chimpanzee, gorilla, orangutan, gibbon; Bazwinsky et al, 2005 ; Hilbig et al, 2009 ; Kim et al, 2014 ), and exhibits rather unique structural and biophysical adaptations to serve its function, it seems most likely that this nucleus would also be present in the human SOC. To suggest otherwise would require that humans have miraculously developed, de novo , new mechanisms for instance for sound localization.…”

“…Furthermore, we suggest that investigations of the primate auditory brainstem provide evidence that support the existence of the MNTB in the human brain. Specifically, the MNTB in rhesus and baboon is located amongst axons of the trapezoid body ( Strominger, 1978 ) and these neurons are IR for parvalbumin and calbindin and are associated with large SYN+, CR or VGLUT1 positive calyx endings ( Bazwinsky et al, 2005 ; Kim et al, 2014 ). Further, rhesus MNTB neurons are Kv3.1b positive and are associated with perineuronal nets ( Hilbig et al, 2007 ).…”

Structural refinement of the auditory brainstem neurons in baboons during perinatal development

“…However, most studies using rodents have focused on After hearing onset, spatial refinement of excitatory and inhibitory synaptic inputs on the dendritic and somatic surface is critical for MSO neurons to allow synaptic integration for finetuning of the coincidence mechanisms 15,16 . Similar to the MSO in gerbils 15 , the distribution of inhibitory inputs in MSO was refined after hearing onset in baboons, in the uterus and throughout fetal development 25 . Before hearing onset in E-pre neonates, both VGluT1 and VGAT signals were detected at the somata and dendrites without a distinguishable pattern.…”

“…Baboon auditory brainstems labeled with MAP2 show prominent MNTB, MSO, and LSO organized in the medial to lateral directions in consecutive order. The MNTB was the most medial nucleus, with a round shape located along the auditory fibers that cross the midline of the brainstem 25 . The MSO, a dorsoventrally orientated column of neurons, was located laterally to the MNTB.…”

“…Morphologic development of MSO neurons, including dendritic structure, may be regulated by synaptic inputs and integration 27,28 . We previously demonstrated that spatial refinement of synaptic inputs on the dendritic and somatic surfaces of the MSO neuron from baboon neonates occur after hearing onset 25 . In the MSO of extremely preterm baboons, the vesicular GABA transporter (VGAT), which is a marker for inhibitory terminals, was visible on both cell bodies and dendrites; in term baboons, the MSO VGAT and vesicular glutamate transporter 1 (VGluT1, a marker for excitatory nerve terminals) puncta were concentrated on the soma and dendrites of MSO neurons, respectively ( Figure 3A, B Figure 3C).…”