Species Differences in the Organization of the Ventral Cochlear Nucleus

The mammalian cochlear nuclei (CN) consist of two major subdivisions, the dorsal (DCN) and ventral (VCN) nuclei. We previously reported differences in the structural and neurochemical organization of the human DCN from that in several other species. Here we extend this analysis to the VCN, considering both the organization of subdivisions and the types and distributions of neurons. Classically, the VCN in mammals is composed of two subdivisions, the anteroventral (VCA) and posteroventral cochlear nuclei (VCP). Anatomical and electrophysiological data in several species have defined distinct neuronal types with different distributions in the VCA and VCP. We asked if VCN subdivisions and anatomically defined neuronal types might be distinguished by patterns of protein expression in humans. We also asked if the neurochemical characteristics of the VCN are the same in humans as in other mammalian species, analyzing data from chimpanzees, macaque monkeys, cats, rats and chinchillas. We examined Nissl‐ and immunostained sections, using antibodies that had labeled neurons in other brainstem nuclei in humans. Nissl‐stained sections supported the presence of both VCP and VCA in humans and chimpanzees. However, patterns of protein expression did not differentiate classes of neurons in humans; neurons of different soma shapes and dendritic configurations all expressed the same proteins. The patterns of immunostaining in macaque monkey, cat, rat, and chinchilla were different from those in humans and chimpanzees and from each other. The results may correlate with species differences in auditory function and plasticity. Anat Rec, 301:862–886, 2018. © 2017 Wiley Periodicals, Inc.     

Effects of Salicylate on the Inflammatory Genes Expression and Synaptic Ultrastructure in the Cochlear Nucleus of Rats

Aspirin (salicylate), as a common drug that is frequently used for long-term treatment in a clinical setting, has the potential to cause reversible tinnitus. However, few reports have examined the inflammatory cytokines expression and alteration of synaptic ultrastructure in the cochlear nucleus (CN) in a rat model of tinnitus. The tinnitus-like behavior of rats were detected by the gap prepulse inhibition of acoustic startle (GPIAS) paradigm. We investigated the expression levels of the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), N-methyl d-aspartate receptor subunit 2A (NR2A) mRNA and protein in the CN and compared synapses ultrastructure in the CN of tinnitus rats with normal ones. GPIAS showed that rats with long-term administration of salicylate were experiencing tinnitus, and the mRNA and protein expression levels of TNF-α and NR2A were up-regulated in chronic treatment groups, and they returned to baseline 14 days after cessation of treatment. Furthermore, compared to normal rats, repetitive salicylate-treated rats showed a greater number of presynaptic vesicles, thicker and longer postsynaptic densities, increased synaptic interface curvature. These data revealed that chronic salicylate administration markedly, but reversibly, induces tinnitus possibly via augmentation of the expression of TNF-α and NR2A and cause changes in synaptic ultrastructure in the CN. Long-term administration of salicylate causes neural plasticity changes at the CN level.     

Dynamic Properties of Primary Auditory Fibers Compared with Cells in the Cochlear Nucleus

The dynamic properties of the responses of single primary auditory fibers were compared with those of single cells in the cochlear nucleus. The stimuli were tones (at the unit's characteristic frequency, CF) that were amplitude-modulated with pseudorandom noise. The dynamic properties were described by the cross-covariance and integrated cross-covariance functions between the recorded discharge rate and the modulation. These two measures have earlier been shown to be valid approximations of the system's impulse and step response function, i.e. the change in discharge rate in response to a short impulsive increase (or decrease) in the stimulus intensity and a step increment (or decrement) in the stimulus intensity. The cross-covariance function computed from the responses of fibers had a narrower peak than that of cells indicating that a brief change in stimulus intensity gives rise to a faster change in the discharge rate of fibers than that of cells. The modulation of the discharge rate of cells for a certain degree of amplitude modulation of the sound is usually greater than that of fibers. The range of stimulus intensities where a change in stimulus intensity gives rise to a change in discharge rate is smaller for fibers (about 30 dB) than what was shown earlier for cells (70–80 dB). The cross-covariance function computed from the slow wave responses recorded from the surface of the cochlear nucleus in response to an amplitude-modulated tone has individual peaks that reflect distinct classes of units with regard to latency of unit discharges.     

Collateral Projections from the Lateral Parabrachial Nucleus to the Central Amygdaloid Nucleus and the Ventral Tegmental Area in the Rat

Lateral parabrachial nucleus (LPB) is a critical region in the integration and transmission of peripheral nociceptive information. The parabrachio-amygdaloid (P-Amy) pathway and parabrachio-ventral tegmental area (P-VTA) pathway is thought to be significant in regulation of pain-related negative emotions. In present study, retrograde tract tracers Fluoro-gold (FG) and tetramethylrhodramine-dextran (TMR) were stereotaxically injected into the right central amygdaloid nucleus (CeA) and right VTA, respectively. Then, part of these rats were performed with the spare nerve injury (SNI) in the controlateral side of FG and TMR injection. Afterwards, double- or triple-immunofluorescent histochemistry was used to examine FG/TMR double- and FG/TMR/FOS or FG/TMR/CGRP triple-labeled neurons in the LPB. The results showed that all of FG, TMR single- and FG/TMR double-labeled neurons were distributed in the LPB bilaterally with an ipsilateral predominance. The proportion of FG/TMR double-labeled neurons to the total number of FG- and TMR-labeled neurons was 10.78% and 13.07%, respectively. Nearly all of the FG/TMR double-labeled neurons (92.67%) showed calcitonin gene-related peptide (CGRP) immunopositive. On the other hand, in the SNI rats, about 89.49% and 77.87% of FG- and TMR-labeled neurons were FG/FOS- and TMR/FOS-positive neurons; about 93.33% of the FG/TMR double-labeled neurons were FOS-LI. Our results suggest that the part of CGRP immunopositive neurons in the LPB send projection fibers to both the CeA and VTA by the way of axon collaterals, which are activated by the nociceptive stimulation in the SNI condition, and may play an important role in the transmission of peripheral nociceptive information. Anat Rec, 302:1178–1186, 2019. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.     

Dynamic Properties of Excitation and Inhibition in the Cochlear Nucleus

The dynamic properties of inhibition and excitation of single units in the cochlear nucleus were studied using tones that were amplitude modulated either sinusoidally or with pseudorandom noise. The cross-correlation analysis of the unit discharge rate and the pseudorandom noise modulation of the stimuli showed that the dynamic properties determined from the responses to a single modulated excitatory tone (at CF), to a modulated excitatory tone together with an unmodulated inhibitory tone (above CF), and to a modulated inhibitory tone together with an unmodulated excitatory tone were almost identical with regard to latency as well as to delay of the peak of the cross-covariance function. On the basis hereof it is inferred that the inhibition is either a cochlear phenomenon or that it is transmitted over pathways with identical temporal properties as those of the excitation. When 2 tones were presented simultaneously the modulation of the excitatory tone usually gave a higher degree of modulation of the discharge rate than did modulation of an inhibitory tone. Addition of an unmodulated inhibitory tone to a modulated tone at CF resulted in an extension of the range of intensities over which the maximal gain was relatively constant. In many units this range extended from about 10 dB above the unit's threshold to 60 dB or more above.     

Effect of Cooling on Synaptic Transmission through the Cuneate Nucleus

The synaptic transmission through the cuneate nucleus was studied during local cooling of the dorsal column region. Field potentials, recorded from the surface as well as inside the nucleus, were greatly increased during moderate cooling (to 30–25^o C) but diminished rapidly if the cuneate temperature fell below about 20^o C. The increase was most evident for the afferent fibre volley potentials, but large changes of synaptic potentials (N-wave) were regularly seen as well. The increase (up to several hundred per cent) was partly rate-dependent since fast cooling gave larger increases than slower cooling did. In spite of the greatly increased N-wave, the transmission through the nucleus was always reduced. This was tested in various ways: measurement of the latency and probability of firing of single units, “killed end”–recording from lemniscal fibres as a measure of number of discharging cuneate neurones, and measurement of the size of thalamic and cortical field potential produced by impulses relayed through the cuneate nucleus. The reduced transmission was most likely due to a greatly increased synaptic delay, with slowing of conduction along the terminal branches of the afferent fibres as a contributing factor. On severe cooling blocking of conduction in these branches occurred. During moderate cooling the probability of firing of most relay cells remained strikingly high.