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Effects of somatosensory and parallel-fiber stimulation on neurons in dorsal cochlear nucleus.

1. Single units and evoked potentials were recorded in the dorsal cochlear nucleus (DCN) of paralyzed decerebrate cats in response to electrical stimulation at two sites: 1) in the somatosensory dorsal column nuclei (together called MSN below for medullary somatosensory nuclei), which activates mossy-fiber inputs to granule cells in superficial DCN, and 2) on the free surface of the DCN, which activates granule cell axons (parallel fibers) directly. The goal was to evaluate hypotheses about synaptic interactions in the cerebellum-like circuitry of the superficial DCN. A four-pulse facilitation paradigm was used (50-ms interpulse interval); this allows identification of three components of the responses of DCN principal cells (type IV units) to these stimuli. The latencies of the response components were compared with the latency of the evoked potential in DCN, which signals the arrival of the parallel fiber volley at the recording site. 2. The first component is a short-latency inhibitory response; this component is seen only with MSN stimulation and is seen almost exclusively in units also showing the second component, the transient excitatory response. The short-latency inhibitory component precedes the evoked potential. No satisfactory explanation for the short-latency component can be given at present; it most likely reflects a fast-conducting inhibitory input that arrives at the type IV unit before the slowly conducting parallel fibers. 3. The second component is a transient excitatory response; this component is seen with both MSN and parallel fiber stimulation; it is weak and appears to be masked easily by the inhibitory response components. The excitatory component occurs at the same latency as the evoked potential and probably reflects direct excitation of principal cells by granule cell axons. The excitatory component is seen in about half the type IV units for both stimulating sites. With MSN stimulation, the lack of excitation in some units suggests a heterogeneity of cochlear granule cells, with some carrying somatosensory information and some not carrying this information; with parallel fiber stimulation, excitation probably requires the stimulating and recording electrodes to be lined up on the same "beam" of parallel fibers. 4. The third component is a long-lasting inhibitory response that is observed in virtually all type IV units with both MSN and parallel-fiber stimulation; its latency is longer than the evoked potential. Evidence suggests that it is produced by inhibitory input from cartwheel cells. The appearance of this inhibitory component in almost all type IV units can be accounted for by the considerable spread of cartwheel-cell axons in the direction perpendicular to the parallel fibers. 5. The evoked potential and all three components of the unit response vary systematically in size over the four pulses of the electrical stimulus. These results can be accounted for by two phenomena: 1) a facilitation of the granule cell synapses on all cell types that produces a steadily growing response through the four pulses, resembles presynaptic facilitation, and is seen with both MSN and parallel-fiber stimulation; and 2) a strong reduction in the granule cell response between the first and second pulse for MSN stimulation only. This reduction probably occurs presynaptically in the glomerulus or in the granule cell itself and could reflect inhibitory inputs. 6. The response components described above are seen in type IV units recorded in both the fusiform-cell and deep layers of the DCN; this suggests that both pyramidal and giant cells are activated similarly. The simplest interpretation is that both principal cell types are activated by the cerebellum-like circuitry in superficial DCN. Alternatively, because giant cells appear to make limited contact with the granule-cell circuits of superficial DCN, this finding may suggest the existence of currently undescribed granule cell circuits in deep DCN that are si

Animals↗

A modeling study of notch noise responses of type III units in the gerbil dorsal cochlear nucleus.

A computational model of the neural circuitry of the gerbil dorsal cochlear nucleus (DCN), based on the MacGregor's neuromime model, was used to simulate type III unit (P-cell) responses to notch noise stimuli. The DCN patch model is based on a previous computational model of the cat DCN [Hancock, K. E., and H. F. Voigt. Ann. Biomed. Eng. 27:73-87, 1999]. According to the experimental study of Parsons et al. [Ann. Biomed. Eng. 29:887-896, 2001], the responses of gerbil DCN type III units to notch noise stimuli are similar to those of cat DCN type IV units, which are thought to be spectral notch detectors. This suggests that type III units in the gerbil DCN may serve as spectral notch detectors. In this modeling study, a simplified notch noise response plot-spike discharge rate vs. notch cutoff frequency plot-was used to compare model responses to the experimental results. Parameter estimation and sensitivity analysis of three connection parameters within the DCN patch have been studied and shows the model is robust, providing reasonable fits to the experimental data from 14 of 15 type III units examined [work supported by a grant from NIDCD, Boston University's Biomedical Engineering department and Hearing Research Center].

Animals↗

Activation of GIRK channels by muscarinic receptors and group II metabotropic glutamate receptors suppresses Golgi cell activity in the cochlear nucleus of mice.

Granule cells and parallel fiber circuits in the dorsal cochlear nucleus (DCN) play a role in integration of multimodal sensory with auditory inputs. The activity of granule cells is regulated through inhibitory connections made by Golgi cells. Golgi cells in turn probably receive parallel fiber inputs and regulate activity of the DCN. We have investigated the electrophysiological properties of Golgi cells using the whole cell patch-clamp method in slices made from transgenic mice that express green fluorescent protein driven by the promotor of metabotropic glutamate receptor subtype 2. Stimulation of auditory nerve fibers (ANFs) and of parallel fibers evoked glutamatergic excitatory postsynaptic currents (EPSC) through AMPA receptors. The strengths and latencies of these inputs differed, however. ANF stimulation evoked EPSCs after 4.7 +/- 0.4 ms, whereas parallel fiber stimulation evoked EPSCs after 1.4 +/- 0.2 ms that were on average 2.5 times as large. The multiple peaks and prolonged activity suggest the presence of polysynaptic connections between ANFs and Golgi cells. Agonists for group II metabotropic glutamate receptors (mGluRs) and for muscarinic receptors induced membrane hyperpolarization and suppressed the firing of Golgi cells by activating G-protein-coupled inward rectifier K(+) (GIRK) channels. These results strongly suggest that Golgi cells were regulated through the combined activities of glutamatergic and cholinergic synapses, which presumably regulated the temporal firing patterns of granule cells and through them the activity of principal cells of the DCN.

Action Potentials↗

Subthreshold oscillations generated by TTX-sensitive sodium currents in dorsal cochlear nucleus pyramidal cells.

During intracellular recordings in rodent brainstem slice preparations, dorsal cochlear nucleus (DCN) pyramidal cells (PCs) exhibit characteristic discharge patterns to depolarizing current injection that depend on the membrane potential from which the responses are evoked. When depolarized from hyperpolarized potentials, PCs can respond with a short-latency action potential followed by a long silent interval (pauser) or a train of action potentials with a long latency (buildup). During the silent intervals in a pauser or a buildup response, the membrane potential slowly depolarizes towards spike threshold, often exhibiting distinct voltage oscillations of 1-2 mV before the first spike. The subthreshold voltage oscillations were investigated using whole cell recordings from DCN PCs in rat pup (P10-14) brainstem slices. The oscillations were unaffected by excitatory and inhibitory neurotransmitter antagonists, and were not temporally locked to the onset of the depolarization. The oscillations typically became larger as spike threshold was approached, and had a characteristic frequency between 40 and 100 Hz. In the presence of tetrodotoxin (TTX, 500 nM), the oscillations were significantly suppressed, and could not be evoked at any voltage below or above spike threshold. The oscillations were not blocked by phenytoin or Cd2+, but they were affected by prior activity in the neuron for approximately 1 s. We conclude that voltage-gated Na+ channels are required to generate membrane oscillations during the buildup phase. We suggest that the subthreshold oscillations play a role in controlling spike timing in PCs when the membrane potential slowly approaches, or hovers near, spike threshold.

Acoustic Stimulation↗

Linear and nonlinear spectral integration in type IV neurons of the dorsal cochlear nucleus. I. Regions of linear interaction.

The principal neurons of the dorsal cochlear nucleus have complex response properties, many of which are classified as type IV. These units integrate energy in the acoustic signal in a nonlinear fashion; for example, at high sound levels the response to a noise of narrow bandwidth and to a band-reject filtered noise with a spectral notch of the same bandwidth may both be inhibitory. However, the sum of these two stimuli, which is broadband noise (BBN), generally gives an excitatory response. In other situations, linear interactions among stimulus components are observed. In this paper, three regimes of approximate linearity were identified. First, best-frequency (BF) tones and equal-energy narrow noisebands centered at BF evoke almost the same response, which is consistent with a stage of linear filtering followed by a nonlinearity that generates the rate responses of the neuron. Second, for sounds close to threshold (10-15 dB re threshold), energy over the full bandwidth of the unit is integrated linearly. Within this regime, responses to the narrow noiseband and the spectral notch mentioned above do sum to equal the response to BBN. Finally, two noisebands centered at different frequencies, such that their sum is a notch in a broad band of noise, sum linearly at low sound levels; the degree of linearity improves as the separation between the noisebands increases. The results are interpreted in terms of a model of type IV response generation containing two inhibitory interneurons: type II units, which are active for narrowband stimuli, including tones, and the wideband inhibitor, which is active for broadband stimuli. In most cases, the onset of nonlinearity occurs for stimuli that significantly activate the type II inhibitory interneuron.

Acoustic Stimulation↗

Afferent regulation of cytochrome-c and active caspase-9 in the avian cochlear nucleus.

During development, a subpopulation (approximately 30%) of neurons in the avian cochlear nucleus, nucleus magnocellularis (NM), dies following removal of the cochlea. It is clear that neuronal activity coming from the auditory nerve provides trophic support critical for cell survival in the NM. Several aspects of the intracellular signaling cascades that regulate apoptosis have been defined for naturally occurring, or programmed cell death, in neurons. These intracellular cascades involve the extrusion of cytochrome-c from the mitochondria into the cytosol and the subsequent activation of proteolytic caspase cascades, which ultimately act on substrates that lead to the death of the cell. In contrast, the intracellular signaling cascades responsible for deafferentation-induced cell death are not fully understood. In the present series of experiments, the potential extrusion of cytochrome-c from the mitochondria into the cytosol, and the activation of caspases were examined in the NM following deafferentation. Cytochrome-c immunoreactivity increased within 6 h following deafferentation and persisted for at least 3-5 days following surgery. However, cytochrome-c was not detectable within immunoprecipitates obtained from cytosolic fractions of deafferented NM neurons. This suggests that the increased immunoreactivity of cytochrome-c is related to mitochondrial proliferation. As a positive control, cytochrome-c was detected in cytosolic fractions of deafferented NM neurons treated with kainic acid, a substance known to cause cytochrome-c release into the cytosol. In addition, immunoreactivity for downstream active caspase-9 did increase following cochlea ablation. This increase was observed within 3 h following cochlea removal, but was not observed 4 days following surgery, a time point after the dying population of NM neurons have already degenerated. Together, these findings suggest that deafferentation of NM neurons results in caspase activation, but this activation may be cytochrome-c independent.

Animals↗

Mathematical models of cochlear nucleus onset neurons: I. Point neuron with many weak synaptic inputs.

The cochlear nucleus (CN) presents a unique opportunity for quantitatively studying input-output transformations by neurons because it gives rise to a variety of different response types from a relatively homogeneous input source, the auditory nerve (AN). Particularly interesting among CN neurons are Onset (On) neurons, which have a prominent response to the onset of sustained sounds followed by little or no response in the steady-state. On neurons contrast sharply with their AN inputs, which respond vigorously throughout stimuli. On neurons can entrain to stimuli (firing once per cycle of a periodic stimulus) at up to 1000 Hz, unlike their AN inputs. To understand the mechanisms underlying these response patterns, we tested whether an integrate-to-threshold point-neuron model with a fixed refractory period can account for On discharge patterns for tones, systematically examining the effect of membrane time constant and the number and strength of the exclusively excitatory AN synaptic inputs. To produce both onset responses to high-frequency tone bursts and entrainment to a broad range of low-frequency tones, the model must have a short time constant ( approximately 0.125 ms) and a large number (>100) of weak synaptic inputs, properties that are consistent with the electrical properties and anatomy of On-responding cells. With these parameters, the model acts like a coincidence detector with a threshold-like relationship between the instantaneous discharge rates of the output and the inputs. Onset responses to high-frequency tone bursts result because the threshold effect enhances the initial response of the AN inputs and suppresses their relatively lower sustained response. However, when the model entrains across a broad range of frequencies, it also produces short interspike intervals at the onset of high-frequency tone bursts, a response pattern not found in all types of On neurons. These results show a tradeoff, that may be a general property of many neurons, between following rapid stimulus fluctuations and responding without short interspike intervals at the onset of sustained stimuli.

Acoustic Stimulation↗

Immunocytochemical localization of glycine in a subset of cartwheel cells of the dorsal cochlear nucleus in rats.

Glycine is an inhibitory neurotransmitter and a glutamate cofactor for N-methyl-D-aspartate (NMDA) receptors in the central nervous system. The distribution of glycine in the auditory system will therefore provide clues as to synaptic mechanisms underlying auditory signal processing. Previous studies have reported the immunocytochemical presence of glycine in the dorsal cochlear nucleus of a variety of mammals, but the specificity with respect to particular cell types has proven elusive at the light microscopic level. We sought to identify cell types in the superficial regions of the dorsal cochlear nucleus that were immunoreactive to glycine using light and electron microscopy in the rat. At the light microscopic level, glycine immunoreactivity was present in some but not all medium-sized cells in layers I and II. The somata of pyramidal and granule cells were not stained. At the electron microscopic level, using previously published ultrastructural criteria, we examined the glycine-labeled cells and determined that many but not all cartwheel cells were labeled. We also observed unlabeled unipolar brush cells, Golgi cells, and stellate cells. As some of the labeled cells could not be identified, we could not determine whether unipolar brush cells, Golgi cells or stellate cells had both labeled and unlabeled subpopulations. Our observations indicate that within the population of cartwheel cells, only a subset are glycine-immunoreactive.

Animals↗

Neural modeling of intrinsic and spike-discharge properties of cochlear nucleus neurons.

The purpose of this study was to develop neurobiologically plausible models to account for the response properties of several types of cochlear nucleus neurons. Three cell types--the bushy cells, stellate cells, and fusiform cells--were selected because useful data from intracellular recordings were available for these cell types, and because these three cell types exhibit distinct contrasts in their neuronal signal coding strategies. Stellate cells have primarily linear current-voltage (I-V) characteristics, but both bushy and fusiform cells have highly non-linear I-V characteristics. In light of this, we hypothesize that some of these cells have non-linear voltage-dependent conductances which alter their response properties. We modeled the bushy cell membrane conductance as an exponentially increasing function of membrane voltage, that of the fusiform cell as an exponentially decreasing function of the voltage, and that of the stellate cell as being voltage-independent. We have combined the voltage-dependent non-linear conductances of the cell membrane with a simple R-C circuit type of neuron model. These models reproduced the salient features of the experimentally observed I-V characteristics of the cells. In addition, we found that the models reproduced the spike discharge behavior to intracellularly injected current steps. Moreover, a more detailed study of stellate cell 'chopper'-type response patterns yielded hypotheses regarding the nature of the current that must exist at the soma during a pure-tone stimulus in order for the cells to exhibit various chopper subtype patterns, such as chop-S, chop-T, and Oc. The chop-S pattern requires a steady average current level with a relatively small variability during the tone-burst stimulus. The chop-T pattern, in contrast, requires that the current become more irregular during the tone-burst stimulus. The Oc pattern arises, however, when the input is similar to the chop-T case but the intrinsic properties of the cell model have been changed to increase the accommodation of the threshold. The implications of these findings for circuitry in the cochlear nucleus are discussed. Our analysis of these models revealed that this approach can be used to simulate neuronal cell types where I-V characteristics are known but more detailed ion channel data are not known.

Animals↗

Interspike intervals as a correlate of periodicity pitch in cat cochlear nucleus.

Amplitude modulated (AM) signals have often been used as precisely defined partial analogs of speech sounds. This study considers the response to an AM complex with 200% sinusoidal modulation, that is, the amplitudes of the three AM components are equal. By varying the carrier frequency across the entire frequency range of unit response, it is shown that units in the cochlear nucleus of cat are relatively insensitive to variation in the carrier frequency, which is to say that population response to an AM signal at a fixed locus will be widespread. These stimuli and procedures result in the presentation of both harmonic and inharmonic complexes, and thus permit assessment of neural responses for the information needed to make spectral or time-domain pitch matches. It is shown that the reciprocals of the modes (favored intervals) in the interspike interval histogram reflect the first effect of pitch shift, which is defined psychophysically as a proportional shift in pitch to the change in carrier frequency. In particular, interspike intervals of units with a widespread spectral response provide a basis to explain phase and dominant component pitch behavior that early narrow-band pitch theories found problematical. The amplitude of phase locking to individual AM components varies systematically though there are some unexplained variations across the frequency-intensity plane that could be due to combination tones. The unit response to a quasifrequency modulated (QFM) stimulus shows that if pitch is based on interspike intervals, it would remain the smae as pitch for an AM signal. The magnitude of the synchrony response to QFM stimuli is less than to AM stimuli for the majority of cochlear nucleus units; however, there are exceptions.

Animals↗

Direct electrical stimulation of the cochlear nucleus: surface vs. penetrating stimulation.

Prosthetic stimulation of the cochlear nucleus (CN) has been used for rehabilitation of profoundly deaf patients who are not suitable candidates for cochlear implants. The goal of this article was to assess the relative effectiveness of surface vs. penetrating stimulation of the CN. Electrophysiologic and autoradiographic measures were used to study central auditory system activation elicited by direct stimulation of the CN. Eighteen pigmented guinea pigs, divided into three groups, underwent acute implantation of bipolar electrodes in the CN. One group was not stimulated and acted as a control (n = 7). Electrodes were placed on the surface of the CN in one test group (n = 4) and within the CN in a second test group (n = 7). Thresholds for electrically evoked middle latency responses (EMLR) were determined and input/output (I/O) functions were obtained. The two test groups were then pulsed with [14C]-2-Deoxyglucose (2-DG) intramuscularly and stimulated for 1 hour with biphasic; charge-balanced pulses having a total duration of 400 microseconds, a repetition rate of 100/sec, and an amplitude of 200 microA. After stimulation, animals were killed and brains were harvested and prepared for autoradiography using standard techniques. Threshold current for EMLRs in the surface-stimulated group had a mean of 67.5 +/- 23.9 microA (range, 40 to 100 microA). Thresholds for in-depth stimulated group had a mean of 11.4 +/- 3.5 microA (range, 10 to 20 microA). The saturation level of the I/O function for the surface-stimulated group had a mean of 287.5 +/- 41.5 microA (range, 250 to 350 microA). The saturation level for the in-depth stimulated group had a mean of 192.9 +/- 49.5 mciroA (range, 100 to 250 microA). The dynamic range for the surface electrodes had a mean of 13.1 +/- 2.7 dB (range, 9.9 to 15.9 dB), whereas the dynamic range for the penetrating electrodes had a mean of 24.5 +/- 2.6 dB (range, 20 to 28.0 dB). Autoradiographs generated by CNS tissue from stimulated animals demonstrated no significant difference in metabolic activity of the CN between surface and in-depth stimulated groups. However, there were highly significant differences in 2-DG uptake in the contralateral superior olivary complex, contralateral inferior colliculus, and ipsilateral and contralateral lateral lemniscus, with greater uptake in in-depth stimulated preparations. Electrophysiologic and autoradiographic data suggest that a penetrating CN prosthesis is capable of activating the auditory tract at a lower threshold, with a relatively wider dynamic range than a surface prosthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Tuberculoventral cells of the dorsal cochlear nucleus of mice: intracellular recordings in slices.

1. Intracellular recordings were made from six tuberculoventral cells (also called vertical or corn cells) whose identity was confirmed by labeling with biocytin, with the aim of understanding their projection patterns and how their synaptic inputs and their intrinsic electrical properties shape their responses to activation of auditory nerve fibers. 2. The cell bodies, dendrites, and local axonal terminals of all six tuberculoventral cells lay in narrow bands, 70-100 microns wide and parallel to the path of auditory nerve fibers, in the dorsal cochlear nucleus (DCN). Terminals in the ventral cochlear nucleus (VCN) also lay in narrow bands, parallel to the path of auditory nerve fibers in either or both the anteroventral and posteroventral cochlear nuclei. 3. When depolarized with current, tuberculoventral cells fired regularly. The peaks of action potentials were usually overshooting and were followed by two afterhyperpolarizations, resembling other cells of the DCN. Unlike some other cells in the DCN, however, neither of the afterhyperpolarizations resulted in an undershoot of the resting potential in the presence of depolarizing currents stronger than 0.3 nA. The second afterhyperpolarization was more variable than the first. 4. Shocks to the auditory nerve evoked monosynaptic as well as polysynaptic excitation and weak polysynaptic inhibition. These results show that, in addition to receiving excitation directly through auditory nerve fibers, tuberculoventral cells also receive excitation through interneurons. 5. To locate the interneurons in the cochlear nuclei whose activation affects a tuberculoventral cell monosynaptically or polysynaptically, glutamate was applied focally to various loci in the VCN while responses were recorded in a target tuberculoventral cell that was subsequently labeled. Excitation of this tuberculoventral cell arose from a rostrocaudal band in the VCN. 6. The results are consistent with tuberculoventral cells receiving excitatory synaptic input from auditory nerve fibers and from T stellate cells in the VCN. They could be inhibited by D stellate cells in the VCN.

Animals↗

Biotinidase reveals the morphogenetic sequence in cochlea and cochlear nucleus of mice.

Hearing loss affects children with biotinidase deficiency, an inherited metabolic disorder in the recycling of biotin. The deficit appears shortly after birth during development of the auditory system. Using a mouse model, we sought to discover where and when biotinidase is expressed in the normal development of the cochlea and cochlear nucleus. In the process, we reconstructed the normal morphogenetic sequences of the constituent cells. Immunolabeling for biotinidase was localized to neurons and other cells of the adult and immature mouse, including the embryonic precursors of these regions dating from the stage of the otocyst. Its distribution was compared to the particular morphological changes occurring at each developmental stage. Biotinidase was localized in cells and their processes at the critical stages in their proliferation, migration, structural differentiation, and innervation, covering the entire span of their development. The prevalence of immunostaining peaked in the adult animal, including hair cells and ganglion cells of the cochlea and neurons of the cochlear nucleus. The findings suggest that biotinidase plays a role in the normal development of the auditory system. Besides the pattern of localization of biotinidase, this study provides the first systematic account of each developmental stage in a mammalian auditory system.

Aging↗

The responses of single units in the ventral cochlear nucleus of the guinea pig to damped and ramped sinusoids.

Human listeners hear an asymmetry in the perception of damped and ramped sinusoids; the partial loudness of the envelope component is greater than the partial loudness of the carrier component for damped sinusoids. Here we show that an asymmetry also occurs in the physiological responses of most units in the ventral cochlear nucleus to these same sounds. The activity elicited by damped sinusoids is mainly restricted to the beginning of each envelope period, which is not the case for ramped sinusoids. This can be quantified by computing the ratio of the tallest bin of the modulation period histogram to the total number of spikes (the peak-to-total ratio, p/t). Damped sinusoids produce a higher p/t than ramped sinusoids, which demonstrates physiological temporal asymmetry. It is also the case that ramped sinusoids typically elicit more spikes than damped sinusoids. The physiological asymmetry occurs where the perceptual asymmetry is present. It is maximal at modulation half-lives of 4 and 16 ms, greatly reduced at 1 ms and absent at 64 ms. Different unit types exhibit differing degrees of temporal asymmetry. Onset units produce the greatest p/t asymmetry, primary-like units produce the least asymmetry and chopper units are in-between. With regard to total spike count, the maximal asymmetry occurs with chopper units. If primary-like units are assumed to reflect the activity in primary auditory nerve fibres, then there is enhancement of temporal asymmetry in the ventral cochlear nucleus by both onset and chopper units.

Acoustic Stimulation↗

Degenerative alterations in the ventral cochlear nucleus of the guinea pig after impulse noise exposure. A preliminary light and electron microscopic study.

Guinea pigs were exposed to the noise of 40 shots of an alarm pistol held at a distance of about 60 cm. The ventral cochlear nuclei were studied in phase contrast and electron microscopy after both survival periods and longer periods of up to 55 days survival. Marked degeneration of primary cochlear nerve endings and of synapting secondary neurons of the posterior caudal part of the ventral cochlear nucleus (AVCN) and the octupus cell area (OCA) of the posterior ventral cochlear nucleus (PVCN) was found most distinctly after 5-55 days. As criteria of degeneration of the second neuron of the afferent auditory pathway we used: 1. The loss of the synapting nerve endings, mainly 'shrinking". 2. The formation of huge mitochondria in the second order neurons and their dendrites. 3. The phagocytosis by glial cells of nerve endings, of the second order neurons and of their dendrites. After 5 days survival time no distinct changes were found in the granular cell area of PVCN, where as all stages of degeneration could be found in OCA at this time. In the discussion of these findings it is concluded that additional studies of the morphology of the cochlear nuclei seem necessary, as these may lead to a better understanding of the pathology of hearing following heavy noise exposure.

Animals↗

Calcium binding proteins and the AMPA glutamate receptor subunits in gerbil cochlear nucleus.

The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system. The GluR2 subunit confers calcium impermeability to AMPA receptors. Various calcium binding proteins play a role in calcium regulation within the neurons. This study sought to identify possible relationships between calcium binding proteins and glutamate receptor subunits, especially GluR2, in gerbil cochlear nucleus neurons. Our immunohistochemical observations reveal no particular correlation between GluR2 and calbindin; all the cell types show labeling for all the antibodies studied except calretinin. There was coincidence of strong GluR4 and strong parvalbumin staining in octopus cells, although calbindin was also present in these cells. This study suggests a possible relationship between parvalbumin and predominantly GluR4 containing receptors, even when calbindin is present. The absence of a strong inverse correlation between the presence of ionotropic AMPA receptor subunit GluR2 and calbindin suggests a more significant role of non-AMPA ionotropic glutamate receptors or other voltage-gated channels in the regulation of calcium in the neurons of cochlear nucleus. Alternatively, more detailed analysis of receptor composition at particular synapses and the subcellular localization of specific calcium binding proteins may be required.

Animals↗

Temporal coding of 200% amplitude modulated signals in the ventral cochlear nucleus of cat.

The quasiperiodicity in the acoustic waveform in speech and music is a pervasive feature in our acoustic environment. The use of 200% amplitude modulated (AM) signals allows the study of rate and temporal envelope coding using three equal amplitude components, a situation that is frequently approximated in natural vocalizations. The recordings reported here were made in the ventral cochlear nucleus of the cat, a site of auditory signal feature enhancement and the origin of several ascending auditory pathways. The discharge rate vs modulation frequency relation was nearly always all-pass in shape for all unit types indicating that discharge rate is not a code for modulation frequency. Onset cells, especially onset-choppers and onset-I units, exhibited remarkable phase locking to the signal envelope, nearly to the exclusion of phase locking to the AM components. They exhibited lowpass temporal modulation transfer functions (tMTF) that occasionally had corner frequencies greater than 1 kHz. Primary-like, primary-like with notch, and onset-L units all exhibited considerable variability in their coding properties with tMTFs that varied from lowpass to bandpass in shape. The bandpass shape became more frequent with increasing stimulus levels. A common feature in cochlear nucleus units was less sensitivity to the level of the AM stimulus than is present in the auditory nerve. Phase locking to the envelope persisted over a wider range of stimulus levels than rate changes in a subset of the units studied. The tMTFs for a 100% sinusoidally modulated, spectrally-flat noise was similar in amplitude and bandwidth to those obtained for AM stimuli. The tMTF was relatively insensitive to carrier frequencies different than the unit characteristic frequency. AM synchrony vs level curves exhibited systematic shifts that equaled or exceeded dynamic rate shifts that occur with increasing levels of a noise masker. Phase locking to the envelope was robust under a wide variety of signal conditions in all unit types. The ordering of response types based on the maximum of the tMTF is onset-I = onset-chop > choppers = primarylike-with-notch = onset-L > primarylike.

Acoustic Stimulation↗

Single neurons in the spinal trigeminal and dorsal column nuclei project to both the cochlear nucleus and the inferior colliculus by way of axon collaterals: a fluorescent retrograde double-labeling study in the rat.

A number of single neurons in the spinal trigeminal nucleus (STN) and the dorsal column nucleus (DCN) were found to project simultaneously to the cochlear nucleus (CoN) and the external cortex of the inferior colliculus (ICe) by way of axon collaterals. Each rat was injected with Fluoro-Gold (FG) into CoN on one side and with tetramethylrhodamine-dextran amine (TMR-DA) into ICe on the side ipsilateral or contralateral to the FG injection. In these rats, a number of neuronal cell bodies in DCN and the interpolar and caudal subnuclei of STN were double-labeled retrogradely with both FG and TMR-DA, mainly on the side ipsilateral to the FG injection into CoN. These neurons in STN and DCN might mediate somatosensory inputs simultaneously to the two lower brainstem nuclei, CoN and ICe, which constitute the relays of the auditory pathway.

Animals↗