Identification of subdivisions in the medial geniculate body of the guinea pig

The accurate and reliable identification of subdivisions within the auditory thalamus is important for future studies of this nucleus. However, in the guinea pig, there has been no agreement on the number or nomenclature of subdivisions within the main nucleus of the auditory thalamus, the medial geniculate body (MGB). Thus, we assessed three staining methods in the guinea pig MGB and concluded that cytochrome oxidase (CYO) histochemistry provides a clear and reliable method for defining MGB subdivisions. By combining CYO with acetylcholinesterase staining and extensive physiological mapping we defined five separate divisions, all of which respond to auditory stimuli. Coronal sections stained for CYO revealed a moderate to darkly-stained oval core. This area (the ventral MGB) contained a high proportion (61%) of V-shaped tuning curves and a tonotopic organisation of characteristic frequencies. It was surrounded by four smaller areas that contained darkly stained somata but had a paler neuropil. These areas, the dorsolateral and suprageniculate (which together form the dorsal MGB), the medial MGB and the shell MGB, did not have any discernable tonotopic frequency gradient and contained a smaller proportion of V-shaped tuning curves. This suggests that CYO permits the identification of core and belt areas within the guinea pig MGB.     

Long-term changes in middle latency response and evidence of retrograde degeneration in the medial geniculate body after auditory cortical ablation in cats

Short- and long-term changes in the middle latency response (MLR) after bilateral ablation of the auditory cortices were studied in awake cats. The amplitude of the negative peak with a latency of about 15 ms (NA) decreased to 60% of the original value 1 week after ablation (short-term change). In the long term, i.e. 11-30 months, NA either decreased further (decreased group) or remained unchanged (non-decreased group). A histological study with light microscopy revealed degeneration of neurons in the ventral nucleus of the medial geniculate body (MGv) in the decreased group, whereas the neurons in this region were preserved in the non-decreased group. This study suggests that long-term changes in NA reflect retrograde degeneration in the MGv after auditory cortical ablation.     

The human medial geniculate body

The medial geniculate body in non-human species is divided into several parts, each with a different structure, physiological organization, and pattern of connections. Which parts of the human medial geniculate body and which types of neurons might be homologous to those of other species is unknown, and the object of the present study. The cytoarchitecture, fiber architecture, and neuronal organization of the adult human medial geniculate body were studied in Nissl, Golgi, and other preparations. Three divisions, comparable to those in other mammals, were described. The ventral division had a bimodal distribution of somatic sizes in Nissl material which, in Golgi impregnations, may correspond, respectively, to a larger neuron with bushy dendrites and a tufted branching pattern, and a smaller stellate cell with a radiating, spherical dendritic field. The large neurons formed clusters surrounded by a particular pattern of neuropil which, together, constituted fibro-dendritic laminae whose long axis was oriented medio-laterally in parallel sheets or rows. The dorsal division was dominated by small and medium-sized somata representing at least three populations of neurons in the Golgi preparations. The large stellate cell had a radiate dendritic field and a dichotomous branching pattern; an equally large neuron with an elongated, multiangular perikaryon and bushy dendritic arbors forming tufts also occurred. Blended among these larger neurons were many smaller cells with tiny, flask-shaped, round, or drumstick-like perikarya, limited dendritic fields and thin dendrites, and poorly developed stellate or bushy dendritic configurations. In the medial division, larger somata were more common than in the other medial geniculate divisions, but small cells were present in considerable numbers. The fiber architecture and the different kinds of neurons distinguished the three major divisions and the nuclei within them. Thus, the ventral nucleus had long fascicles of axons running parallel to the dendrites of bushy neurons, while the marginal and ovoid nuclei had a different organization. The dorsal division had a more diffuse, irregular arrangement of thinner axons interspersed among bundles of coarser fibers, whereas the medial division was traversed by many coarse preterminal axons passing laterally and dorsally from the brachium of the inferior colliculus; these imparted a striated pattern to the neuropil. Regional variation in cytoarchitecture and the fiber plexus defined several nuclei in each subdivision, except in the medial division, where the density of the staining made further subdivision impossible.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neural architecture of the rat medial geniculate body

The rat medial geniculate body was subdivided using Nissl preparations to establish nuclear boundaries, with Golgi-Cox impregnations to identify projection and local circuit neurons, and in fiber stained material to delineate the fiber tracts and their distribution. Three divisions were recognized (ventral, dorsal and medial); the first two had subdivisions. The ventral division had lateral and medial parts. The main cell type had bushy tufted dendrites which, with the afferent axons, formed fibrodendritic laminae oriented from dorso-lateral to ventro-medial; such laminae were not as regular medially, in the ovoid nucleus. The dorsal division contained several nuclei (dorsal superficial, dorsal, deep dorsal, suprageniculate, and ventrolateral) and neurons with radiating or bushy dendrites; the nuclear subdivisions differed in the concentration of one cell type or another, and in packing density. A laminar organization was present only in the dorsal superficial nucleus. Medial division neurons were heterogeneous in size and shape, ranging from tiny cells to magnocellular neurons; the various cell types intermingled, so that no further subdivision could be made. This parcellation scheme was consistent with, and supported by, the findings from plastic embedded or fiber stained material. There were very few small neurons with locally ramifying axons and which could perform an intrinsic role like that of Golgi type II cells. Their rarity was consistent with the small number of such profiles in plastic embedded or Nissl material and the few GABAergic medial geniculate body neurons seen in prior immunocytochemical work. While similar neuronal types and nuclear subdivisions are recognized in the rat and cat, there may be major interspecific differences with regard to interneuronal organization in the auditory thalamus whose functional correlates are unknown.     

Phase-locked responses to low frequency tones in the medial geniculate body

Over 2500 extracellular single unit recordings were obtained from the medial geniculate body (MGB) of cats anaesthetized with nitrous oxide. Three out of four units were activated by tone bursts, most of them presenting a transient ‘on’ response. Only about 10% of the units showed a sustained excitatory ‘through’ response. Some of these neurons, when activated by low-frequency tone bursts, had discharge synchronized with the phase of the tonal stimulus. Such phase-locked units were principally found in the pars lateralls, but also in the pars magnocellularis and pars ovoidea of the MGB. Significant phase-locking (vector strength R ? 0.5) was observed up to 1000 Hz. About 20% of all units, responding in a sustained fashion to tone bursts below that frequency, were phase-locked. Monaural stimulation led to a shift of the mean phase angle compared to that measured when the tone bursts were delivered simultaneously to both ears. Implications of these experimental results on the synaptic jitter and the information processing through the auditory pathways are discussed.     

下丘不同亚区神经元对纯音刺激的相位锁定反应与潜伏期

目的 研究下丘不同亚区神经元相位锁定反应及其潜伏期，探讨下丘不同亚区时间信息的神经传入差异。方法 采用单极玻璃镀膜钨丝电极记录14只豚鼠下丘单神经元单位的动作电位。双耳给予持续时间200ms的纯音，频率范围为50～3000Hz，用Level—Crossing Detector（Tueker-Daries Technologies）记录神经元单位的特征性频率，频率反应面积（Frequency response area）及围刺激时间柱形图（Perisfimulus time histogram）。在记录结束时，用5μA电流通电10s作一电损伤标记，退出电极，在相距大约1mm处作另一电损伤标记。用计算机软件重建周期柱形图（Penod histogram），并计算向量强度（Vector strength）。利用组织学切片，细胞色素氧化酶染色法染色，重建记录神经元的部位。结果 165个神经元单位的记录部位能通过组织学方法确定，其中11个位于背皮层的外侧部，18个位于外核，134个位于中央核。73％的背皮层神经元单位显示对纯音的相位锁定反应，33％的外核神经元单位发生相位锁定反应，75％的中央核神经元单位显示对纯音的相位锁定反应。在下丘锁相反应神经元中，74％的神经元单位（63／85）的相位随刺激频率变化图为线性，26％的神经元单位呈现为非线性。不同亚区的潜伏期范围为：中央核，4．6～15．4ms[（8．2±2．8）ms]；背皮层，12．8～21．3ms[（16．5±3．4）ms]；外核，12．1～14ms[（13．4±0．9）ms]。结论 下丘三个亚区的相位锁定反应及潜伏期各不相同，其相位锁定的神经传入不同。下丘神经元不仅接受来自下级听觉中枢核团的传入，可能还接受来自上级听觉中枢核团和听觉皮层的相位锁定神经传入。     

Frequency selectivity of the middle latency response

A forward masking paradigm was used to assess the frequency selectivity of the middle latency response (MLR). Tuning curves of the MLR were obtained in unanesthetized gerbils. Changes in the amplitudes of MLR waves A, B, and C with latency values of 10 to 13 ms, 14 to 17 ms, and 20 to 25 ms, respectively, were analyzed as a function of masker frequency and intensity. Tuning curves of the MLR were also compared to tuning curves of the auditory brainstem response (ABR), which was recorded simultaneously with the MLR. The MLR and ABR differed in their response to forward masking. The MLR was reduced in amplitude or eliminated by masker stimuli that had minimal or no effect on the ABR. Forward masking often caused variable and non-monotonic changes in the amplitude of the MLR. Tuning curves of the MLR indicate that the MLR is less frequency selective than the ABR. The MLR is an electrophysiological measure of auditory function central to the auditory brainstem. Therefore, it may provide information concerning central components of normal and pathological auditory function. However, because of the variability of MLR amplitudes with forward masking, tuning curves of the MLR are difficult to obtain and are not efficient for routine measurements of frequency selectivity.     

Transmission delay of phase-locked cells in the medial geniculate body

Over 4000 single unit recordings were obtained from the medial geniculate body (MGB) of nitrous oxide anaesthetized cats. Out of 1600 cells sensitive to tone bursts below 4 kHz, 10% were responding in a sustained manner. From these, 121 were tested for phase-locked responses. The general characteristics of these units have been described in a previous report. The central tendency of the discharges distribution within the period or mean phase angle was studied for many frequencies in 24 phase-locked units. For each of them, the mean phase angle shifts linearly with the frequency. The slope of these phase versus frequency lines is an accurate measure of the transmission delay from the cochlea to the MGB. This delay is a function of the unit's characteristic frequency and shows that the time spread introduced by the cochlea between the high and low frequency components of an acoustic signal is preserved up to the MGB. Subtracting the cochlear delay from this overall delay, the neural delay from the eighth nerve to the MGB was found to be 6.4 ms for neurons having a CF above 300 Hz; it was greater by 3 ms for cells with a CF below that frequency.     

Activity of single medial geniculate units in response to single and double clicks.

The discharge pattern to clicks and the time course and pattern of the click-induced inhibition in the medial geniculate body have been studied by single unit recording technique. The medial geniculate neurones showed a tendency to fire at preferred latencies after a click. A conditioning click caused a reduced number and increased latency of the discharges to a subsequent test click. Provided conditioning click of a certain strength was employed, the inhibition was often cyclic, each period lasting for about 100-150 ms. Clicks could also trigger barbiturate spindles with synchrony between the activity of the medial geniculate body and the primary auditory cortex. Interaction experiments suggest that the triggered and spontaneous spindle activity operate with the same neurones.     

Size and duration of inhibition in the medial geniculate body in unanesthetized cats.

A method which allows repeated micro-electrode recordings from subcortical structures without using any drugs is described. This method was adopted in combination with convential implantation techniques to study click-evoked potentials and inhibitory processes in the auditory system of the cat. The click-evoked potentials in MG were hardly affected by moderate doses of barbiturate and only to a minor degree in the auditory cortex. In the unanaesthetized animal the most significant contribution to the click-evoked inhibition in the auditory system was due to mechanisms in the MG. The inhibition was diminished both in size and duration as compared with the situation in anaesthetized cats. The MG cells showed a tendency to cyclic inhibition in the unanaesthetized cat, but not so regularly as following administration of sodium pentobarbital. The action of barbiturates on the auditory system is discussed.     

Neural coding of repetitive clicks in the medial geniculate body of cat

The activity of 418 medial geniculate body (MGB) units was studied in response to repetitive acoustic pulses in 35 nitrous oxide anaesthetized cats. The proportion of MGB neurons insensitive to repetitive clicks was close to 30%. On the basis of their pattern of discharge, the responsive units were divided into three categories. The majority of them (71%), classified as ‘lockers’, showed discharges precisely time-locked to the individual clicks of the train. A few units (8%), called ‘groupers’, had discharges loosely synchronized to low-rate repetitive clicks. When the spikes were not synchronized, the cell had transient or sustained responses for a limited frequency range and was classified as a ‘special responder’ (21%). Responses of ‘lockers’ were time-locked up to a limiting rate, which varied between 10 and 800 Hz; half of the ‘lockers’ had a limiting rate of locking equal to or higher than 100 Hz. The degree of entrainment, defined as the probability that each click evokes at least one spike, regularly decreases for increasing rates; on the other hand, the precision of locking increases with frequency. The time jitter observed at 100 Hz might be as small as 0.2 ms and was 1.2 ms on average. The population of ‘lockers’ can mark with precision the transients of complex sounds and has response properties still compatible with a temporal coding of the fundamental frequency of most animal vocalizations.     

Intensity functions of single unit responses to tone in the medial geniculate body of cat

Extracellular spike activity was recorded from single units in the medial geniculate body (MGB) of nitrous oxide anaesthetized cats. The responses of 291 units to tone bursts at the characteristic frequency (CF) were studied as a function of stimulus intensity, covering a range from 10 to 100 dB SPL. The proportion of MGB units characterized by a monotonie or a non-monotonic discharge rate-intensity function was 26% and 74%, respectively. In addition, changes of response latency as a function of tone levels were demonstrated to be either monotonie (38% of units) or non-monotonic (62% of units). One third of MGB units showed a change of response pattern with increasing intensities, in similar proportion towards either prevailing excitatory or inhibitory components. The monotonie units tended to differ from non-monotonic ones in addition to their intensity function by showing shorter response latencies, a higher response probability to broad-band stimuli and simpler response patterns. The mean dynamic range of the monotonie unit population was 60 dB, with thresholds ranging from 10 to 90 dB SPL; most discharge rate-intensity functions did not saturate at sound levels of 100 dB SPL. In the population of non-monotonic units, the ‘best’ intensity, defined as the intensity giving the strongest response, ranged between 10 and 100 dB SPL. The present results suggest that the intensity could be signaled by the mean firing rate of a restricted population of monotonie units or place coded by the distribution of maximally activated non-monotonic units which are broadly tuned to different intensities.     

Activation of presynaptic GABAB receptors modulates GABAergic and glutamatergic inputs to the medial geniculate body

The medial geniculate body (MGB) receives ascending inputs from the inferior colliculus and descending inputs from the auditory cortex. In the present study, we intended to determine whether activation of presynaptic GABA(B) receptors modulates GABAergic and glutamatergic inputs to the MGB with whole-cell patch-clamp recordings in brain slices of the rat. To evoke a synaptic response, we electrically stimulated the ascending and descending inputs to MGB neurons with bipolar electrodes placed on the brachium of the inferior colliculus and the superior thalamic radiation. To isolate presynaptic mechanisms, we blocked the effects of postsynaptic GABA(B) receptors by filling recording electrodes with the internal solution containing cesium and QX-314. The activation of presynaptic GABA(B) receptors by exogenous agonist was shown to modulate synaptic inputs to the MGB as demonstrated by that (1) baclofen, a GABA(B) receptor agonist, reversibly suppressed both inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) and this suppressive effect could be blocked by CGP35348, a GABA(B) receptor antagonist, (2) baclofen significantly increased the ratio of IPSCs or EPSCs elicited by paired-pulse stimulation, and (3) baclofen depressed EPSCs and IPSCs in response to repetitive stimulation. The activation of presynaptic GABA(B) receptors by endogenously released GABA was shown to modulate the synaptic transmission as demonstrated by that CGP55845, another GABA(B) receptor antagonist, increased the ratio of IPSCs to paired-pulse stimulation in young (P8-10) rats, although not in juvenile (P15-18) rats. Our study provides electrophysiological evidence for the presence of functional presynaptic GABA(B) receptors in the MGB and suggests an age-dependent role of these receptors in the synaptic transmission in this central auditory region.     

Frequency organization and cellular lamination in the medial geniculate body of the rabbit

Cellular laminae within the tonotopically organized ventral division of the medial geniculate body (MGV) of the cat have been proposed as the anatomical substrate for physiologically defined isofrequency contours. In most species, the laminae are not visible with routine Nissl stains, but are defined by the dendritic fields of principal cells and the terminal arbors of afferents arising from the inferior colliculus. In the present study, we have used the rabbit to directly examine the relationship between the laminar and tonotopic organization of the MGV. Best frequency maps of the MGV in anesthetized adult New Zealand white rabbits were generated from cluster responses recorded at 30-100 microm intervals to randomly presented tone bursts. Parallel vertical penetrations, roughly perpendicular to the laminae, revealed a low-to-high frequency gradient within the MGV. Non-laminated regions of the ventral division, generally found at the rostral or caudal poles, did not demonstrate a systematic frequency gradient. In contrast to a predicted smooth gradient, best frequencies shifted in discrete steps across the axis of the laminae. A similar step-wise frequency gradient has been shown in the central nucleus of the inferior colliculus of the cat. It is proposed that the central laminated core of the MGV represents an efficient architecture for creating narrow frequency filters involved in fine spectral analysis.     

Encoding of alternating acoustical signals in the medial geniculate body of guinea pigs

In unanaesthetized guinea pigs 102 single units of the medial geniculate body were recorded under acoustical stimulation with alternating noise and tone impulses. The temporal parameters of the signals were chosen in close relation to psychoacoustical pulsation-threshold measurements. Most units showed a strong interaction between the responses of the non-simultaneously presented signal components (temporal suppression). The phasic part of each impulse-evoked response was more affected by the suppression than the tonic part. Thus, two regions of responsiveness could be verified: a region of pure tonic discharge and a region of tonic and phasic discharge. The borderline between both regions was defined as ‘on-threshold’.The temporal suppression effect of the discharge rate did depend on impulse duration, impulse shape, gap duration, and the levels of the signals components. The overall unit-response characteristic — especially the lack of temporal onset information — suggested a close relation between psychoacoustical pulsation threshold and physiological ‘on-threshold’.     

Functional organization of the medial division of the medial geniculate body of the cat: tonotopic organization, spatial distribution of response properties and cortical connections

The discharge properties of 735 single units located in the pars magnocellularis (M) of the medial division of the medial geniculate body (MGB) were studied in 23 nitrous oxide anesthetized cats in response to simple acoustic stimuli (clicks, noise and tone bursts). A systematic decrease of single unit characteristic frequencies (CF) was observed along electrode track portions crossing M from dorso-medial to ventro-lateral. These data indicate that M is tonotopically organized with an arrangement of low CF units latero-ventrally and high CF units dorso-medially. This preferential arrangement of single units as a function of their CF was consistent with the location and orientation of clusters of labeled cells in M resulting from wheat-germ agglutinin labeled with horseradish peroxidase (WGA-HRP) injections in CF defined loci in the anterior (AAF) or primary (AI) auditory cortical fields. The quality of the tonotopic arrangement was low caudally and increased in the rostral direction, indicating that this tonotopicity concerns mainly the anterior half of M. Response latencies to clicks, noise and tone bursts were on average longer in the posterior part of M than in its anterior part. Time-locking of discharges in response to repetitive acoustic pulses was more frequent anteriorly than posteriorly and the upper limiting rate of locking was on average higher rostrally (up to 200-300 Hz). In contrast, other response properties such as responsiveness to the various combinations of simple acoustic stimuli, response patterns and tuning were more randomly distributed in M, showing the whole range of response properties seen in the MGB. Data derived from several injections of WGA-HRP performed in distinct auditory cortical fields in several animals indicated that M projects to the tonotopic cortical fields (AAF, AI and PAF) as well as to the non-tonotopically organized secondary auditory cortex (AII). The contribution of M to the total thalamic input reaching each field of the auditory cortex was quantitatively more important for AAF (30%) and PAF (20%) than for AI and AII (about 10% each).     

Differential age effects for components of the adult auditory middle latency response.

The middle latency components of the auditory evoked response were obtained from a young (20-24 years of age) and an older (51 to 71 years of age) group of normal-hearing, healthy female subjects. Recording procedures and stimulus repetition rates were chosen to promote the resolution of both Pa and Pb. The absolute and peak-to-peak amplitudes of Pa and Pb were significantly larger for the older subjects at all stimulus rates. An amplitude reduction of Pb with increasing stimulus rate was much more pronounced for the young than for the older subjects. This, combined with a shorter latency for Pb in the older subjects, may have contributed to partial and/or complete fusion of Pa and Pb observed in 10 of the 17 older subjects. An apparent positive shift in the response baseline for older subjects also may have contributed to the age-related amplitude effects.     

Effects of age on the adult auditory middle latency response

The middle latency components of the auditory evoked response were obtained from a group of normal-hearing, healthy female subjects from 22 to 68 years of age. Recordings were made at several intensity levels to assess the level-dependence of any age-related effects. Cross-sectional analyses revealed that the amplitude of component Pa grows linearly with age, becoming significantly larger in older (50-68 years of age) compared to younger (22-37 years) subjects. The amplitude-intensity function is steeper in the older subjects by a factor of two. Correlational analyses suggested that at higher intensity levels age accounts for about 20% of the variance in the amplitude of Pa. A positive shift in response baseline was observed in the older subjects, and could contribute to the age-related increase in the absolute amplitude of Pa. However, a similar increase in the peak-to-peak and area measures of Pa suggests that some of the increase in the magnitude of Pa is independent of baseline shift. A confounding of age and hearing sensitivity in this study makes it difficult to interpret the age-related effects as strictly central in nature.     

Neural correlates of cubic difference tones in the medial geniculate body of the cat

Single unit responses to the cubic difference tone CDT (2f₁ ? f₂ = CF) and the difference tone DT (f₂ ? f₁ = CF) were studied in the medial geniculate body (MGB) of the cat. Out of 66 units tested with CDT stimuli and having characteristic frequencies (CF) below 10 kHz, 77% gave a response to the two-tone combination stimulus. The component tones when presented alone evoked no responses, or in some cases a response pattern that was different from the one observed for the combination tone. The CDT response pattern was always similar to that seen for a pure tone at the CF. The threshold of response for the CDT was 10–70 dB higher than for a pure tone stimulus at the CF.The few units which were phase-locked could be synchronised with the CF, CDT, or DT, depending on the particular stimulus conditions. The index of synchrony was in many cases found to be higher for CDT responses than for a pure tone at CF.     

Origins of medial geniculate body projections to physiologically defined zones of rat primary auditory cortex

Medial geniculate body neurons projecting to physiologically identified subregions of rat primary auditory cortex (area 41, Te1) were labeled with horseradish peroxidase in adult rats. The goals were to determine the type(s) of projection neuron and the spatial arrangement of these cells with respect to thalamic subdivisions. Maps of best frequency were made with single neuron or unit cluster extracellular recording at depths of 500–800 μm, which correspond to layers III–IV in Nissl preparations. Tracer injections were made in different cortical isofrequency regions (2, 11, 22, or 38 kHz, respectively). Labeled neurons were plotted on representative sections upon which the architectonic subdivisions were drawn independently. Most of the cells of origin lay in the ventral division in every experiment. Injections at low frequencies labeled bands of neurons laterally in the ventral division; progressively more rostral deposits at higher frequencies labeled bands or clusters more medially in the ventral division, and through most of its caudo-rostral extent. Medial division labeling was variable. Labeled cells were always in the lateral half of the nucleus and were often scattered. There were few labeled cells in the dorsal division. Seven types of thalamocortical neuron were identified: ventral division cells had a tufted branching pattern, while medial division neurons have heterogeneous shapes and sizes and were larger. Dorsal division neurons had a radiate branching pattern. The size range of labeled neurons spanned that of Nissl stained neuronal somata. Area 41 may receive two types of thalamic projection: ventral division input is strongly convergent, highly topographic, spatially focal, and restricted to one type of neuron only, while the medial division projection is more divergent, coarsely topographical, involves multiple cortical areas, and has several varieties of projection neuron. Despite species differences in local circuitry, many facets of thalamocortical organization are conserved in phylogeny.