Principal cells of the brainstem's interaural sound level detector are temporal differentiators rather than integrators.

The brainstem's lateral superior olive (LSO) is thought to be crucial for localizing high-frequency sounds by coding interaural sound level differences (ILD). Its neurons weigh contralateral inhibition against ipsilateral excitation, making their firing rate a function of the azimuthal position of a sound source. Since the very first in vivo recordings, LSO principal neurons have been reported to give sustained and temporally integrating 'chopper' responses to sustained sounds. Neurons with transient responses were observed but largely ignored and even considered a sign of pathology. Using the Mongolian gerbil as a model system, we have obtained the first in vivo patch clamp recordings from labeled LSO neurons and find that principal LSO neurons, the most numerous projection neurons of this nucleus, only respond at sound onset and show fast membrane features suggesting an importance for timing. These results provide a new framework to interpret previously puzzling features of this circuit.

Anatomy of the auditory thalamocortical system in the Mongolian gerbil: nuclear origins and cortical field-, layer-, and frequency-specificities.

Knowledge of the anatomical organization of the auditory thalamocortical (TC) system is fundamental for the understanding of auditory information processing in the brain. In the Mongolian gerbil (Meriones unguiculatus), a valuable model species in auditory research, the detailed anatomy of this system has not yet been worked out in detail. Here, we investigated the projections from the three subnuclei of the medial geniculate body (MGB), namely, its ventral (MGv), dorsal (MGd), and medial (MGm) divisions, as well as from several of their subdivisions (MGv: pars lateralis [LV], pars ovoidea [OV], rostral pole [RP]; MGd: deep dorsal nucleus [DD]), to the auditory cortex (AC) by stereotaxic pressure injections and electrophysiologically guided iontophoretic injections of the anterograde tract tracer biocytin. Our data reveal highly specific features of the TC connections regarding their nuclear origin in the subdivisions of the MGB and their termination patterns in the auditory cortical fields and layers. In addition to tonotopically organized projections, primarily of the LV, OV, and DD to the AC, a large number of axons diverge across the tonotopic gradient. These originate mainly from the RP, MGd (proper), and MGm. In particular, neurons of the MGm project in a columnar fashion to several auditory fields, forming small- and medium-sized boutons, and also hitherto unknown giant terminals. The distinctive layer-specific distribution of axonal endings within the AC indicates that each of the TC connectivity systems has a specific function in auditory cortical processing.

Characterization of cochlear nucleus principal cells of Meriones unguiculatus and Monodelphis domestica by use of calcium-binding protein immunolabeling.

Antibodies directed against calcium-binding proteins (CaBPs) parvalbumin, calbindin-D28k and calretinin were used as neuronal markers to identify and characterize different principal cell types in the mammalian cochlear nucleus. For this purpose, double immunofluorescence labeling and the combination of CaBP-labeling with pan-neuronal markers were applied to analyze the CaBPs distribution in neurons of the cochlear nucleus (CN) of the Mongolian gerbil (Meriones unguiculatus) and the gray short-tailed opossum (Monodelphis domestica). Despite of the fact, that these two mammalian species are not closely related, principal cell types in the CN of the two species showed many corresponding morphological features and similarities in immunolabeling of the CaBPs. Parvalbumin seems not to be suited as a differential neuronal marker in the CN since it is expressed by almost all neurons. In contrast, calbindin and calretinin were more restricted to specific cell types and showed a mostly complementary labeling pattern. As one of the most interesting findings, calbindin and calretinin were predominantly found in subpopulations of globular bushy cells and octopus cells in the ventral CN. Such a neuron-specific CaBP-expression in subpopulations of morphologically defined cell types argues for a more refined classification of CN cell types in Meriones and Monodelphis. Additionally, other cell types (cartwheel cells, unipolar brush cells, fusiform cells) were marked with calbindin or calretinin as well. Calretinin staining was predominantly observed in auditory nerve fibers and their endings including endbulbs of Held in Meriones. Spherical bushy cells showed a different calretinin-immunolabeling in Meriones and Monodelphis. This species-specific difference may be related to adaptive differences in auditory function.

Early experience and domestication affect auditory discrimination learning, open field behaviour and brain size in wild Mongolian gerbils and domesticated laboratory gerbils (Meriones unguiculatus forma domestica).

The influence of early experience and strain differences on auditory discrimination learning, open field behaviour and brain size was investigated in wild-type Mongolian gerbils (strain Ugoe:MU95) raised in the wild (wild F-0) or in the laboratory (wild F-1) and in domesticated Laboratory Gerbils (LAB). Adult males were conditioned for 10 days in a shuttle box go/no-go paradigm to discriminate two frequency-modulated tones. Significant learning was established within 5 days in wild F-0 and within 3 days in wild F-1 and LAB. Spontaneous jumps in the shuttle box (inter-trial crossings) were frequently seen in wild F-0 and F-1, but rarely in LAB. All groups exhibited nearly the same ability to remember after 2 weeks without training. In the open field test applied on 5 consecutive days, no differences in locomotion patterns and inner field preferences were found. Rearing frequency decreased over 5 days in wild gerbils. Running distances (4-6m/min) were similar in wild F-0 and LAB, but higher in wild F-1. The ratio of brain size to body weight did not differ between wild F-0 and F-1, but was 17.1% lower in LAB. Correspondingly high brain weights in wild F-1 and F-0 support our domestication hypothesis and negate any serious effect of early experience or captivity on brain size in Mongolian gerbils. In contrast, wild F-1 raised in the laboratory show a rapid improvement in learning performance, indicating that early experience rather that genetic differences between strains affect shuttle box discrimination learning in gerbils.

Ultrastructure indicative of ion transport in tectal, Deiters, and tunnel cells: differences between gerbil and chinchilla basal and apical cochlea.

Ultrastructural examination revealed an epithelium of about five tectal cells (TCs) roofing the outer tunnel (OT) in the mid to upper, but not the basal, region of gerbil and chinchilla cochlea. Structures in TCs that are apparently specialized for retrieval of K(+) released into tunnel fluid from outer hair cells (OHCs) include surface fimbriae in the gerbil and canalicular reticulum in the chinchilla. A tunnel roof of organelle-rich TCs appeared to be better equipped for ion resorption than a roof composed of organelle-poor Hensen cells (HCs). Fimbriae, filopodia, and the cell body of TCs descended to contact the third Deiters cell (DC3) in the gerbil, and the hypertrophied DC3 phalanx rose to contact TCs in the chinchilla, which suggests a solute exchange between TCs and DCs. Previously unrecognized structures that are speculated to provide ATP ligand for cochlear purinoreceptors occurred in the chinchilla DC and gerbil TC. The observation of a microtubule stalk in DCs indicated that they also function in cochlear mechanics. A newly delineated lateral tunnel cell (LTC) intervened between the DC3 and HC in both species. The apicomedial plasmalemma of all DCs fitted closely to the base of OHCs and enveloped afferent nerves. The morphologic specializations reported here provide further support for the proposed transcellular lateral flow route for K(+) currents generated by sound exposure and neural activity. The previously demonstrated expansion of Boettcher cells, outer sulcus cell roots, type Il and IV fibrocytes, and apical microvilli on HCs and Claudius cells (CCs) in the base of the cochlea is postulated here to mediate a basal parallel current that could supply the increased K(+) transport required for the basally elevated electric potential (EP).

Superposition of horseshoe-like periodicity and linear tonotopic maps in auditory cortex of the Mongolian gerbil.

The segregation of an individual sound from a mixture of concurrent sounds, the so-called cocktail-party phenomenon, is a fundamental and largely unexplained capability of the auditory system. Speaker recognition involves grouping of the various spectral (frequency) components of an individual's voice and segregating them from other competing voices. The important parameter for grouping may be the periodicity of sound waves because the spectral components of a given voice have one periodicity, viz. fundamental frequency, as their common denominator. To determine the relationship between the representations of spectral content and periodicity in the primary auditory cortex (AI), we used optical recording of intrinsic signals and electrophysiological mapping in Mongolian gerbils (Meriones unguiculatus). We found that periodicity maps as an almost circular gradient superimposed on the linear tonotopic gradient in the low frequency part of AI. This geometry of the periodicity map may imply competitive signal processing in support of the theory of "winner-takes-all".

Anatomical and functional connections among cell groups in the gerbil brain that are activated with ejaculation.

Based on Fos expression, four areas of the gerbil brain are activated with ejaculation, i.e., the posterodorsal preoptic nucleus (PdPN), the lateral part of the posterodorsal medial amygdala (MeApd), the medial cell group of the sexually dimorphic preoptic area (medial SDA), and the parvicellular part of the subparafascicular thalamus (SPFp). The SPFp and medial SDA also express Fos earlier in the context of mating. To study connections among these areas, we injected one with FluoroGold and assessed the colocalization of FluoroGold and mating-induced Fos in the others. To determine if any of these areas activates the others, we lesioned one unilaterally and measured mating-induced Fos ipsilaterally and contralaterally in the others. Half of the SPFp cells projecting to the medial SDA, PdPN, and MeApd were activated with mating. SPFp lesions also decreased Fos expression in those areas. However, those areas do not project to the SPFp or affect its Fos expression with mating. Projections from the lateral MeApd to the medial SDA and PdPN, and from the medial SDA to the lateral MeApd, were also activated with mating, but lesions in these areas did not affect Fos expression in the others. Because 32-50% of the mating-activated cells in the SPFp participated in each SPFp projection identified, projections may have been identified for all of the mating-activated cells in the SPFp. In contrast, most of the mating-activated cells in the lateral MeApd, PdPN, and medial SDA do not participate in any projection studied, suggesting that they are either interneurons or project elsewhere.

Laterally asymmetrical cell number in a sexually dimorphic nucleus in the gerbil hypothalamus is correlated with vocal emission rates.

A lateralized relationship between the total volume of a discrete area in a hypothalamic, sexually differentiated nucleus (SDApc) and stereotyped vocalization exists in male Mongolian gerbils. In this present study, using unbiased stereological methods, two cytoarchitectural estimates of the SDApc's structure, neuron number, and nuclear volume were found to be sexually differentiated and also laterally asymmetrical in adult males. In ovariectomized females receiving exogenous testosterone, no cytoarchitectural component was asymmetrical. Significantly, the estimate of neuron number, but not nuclear volume, in the left SDApc of males was correlated with vocal emission rate. The authors conclude that a specific, sex-related cytoarchitectural SDApc parameter shows left-right asymmetry, suggesting the SDApc has an intimate role in mediating hemispheric specialization rather than just being an end point index of individual structural variability.

Cells of origin, thalamic relay and termination of the external cuneothalamocortical tract in the gerbil.

The present study is concerned with the connections of the external cuneate nucleus (ECN) in the gerbil following an injection of horseradish peroxidase (HRP) into the ventralis posterior pars oralis (VPLo) or adjacent nuclei of the thalamus. The number, soma size and distribution of the retrograde-labelled ECN neurons were studied and quantified. The application of two retrograde fluorescent tracers was also used to determine whether the ECN neurons would project to the thalamus as well as to the cerebellum through their collaterals. The HRP-positive ECN neurons projecting to the thalamic VPLo were confined to the contralateral caudal half of the ECN, primarily within the intermediate portion represent the forearm and arm territories with a small part of the thoracic and shoulder areas. Labelled neurons were classified into small and medium-sized cells. The majority (96%) of the external cuneothalamic neurons were of the small variety. No double-labelled cells were detected in the ECN following injections of Rhodamine-labelled latex microspheres and Fast blue into the cerebellum and thalamus respectively, suggesting that the ECN neurons projecting to the thalamus form a separate cell group different from those projecting to the cerebellum. The injected HRP into the VPLo was also transported in an anterograde direction by the thalamocortical fibers. The HRP-labelled axonal terminals were distributed within motor area 4 and the dysgranular zones (DZs) of the primary somatosensory cortex (SmI), reaching the deep layers IV and VI as well as superficial layer I. The external cuneothalamocortical pathway shown in the present study may be related to the proprioceptive feedback control of the coordinating motor activity, especially during forelimb muscle movement.

Efferent projections of the sexually dimorphic area of the gerbil hypothalamus: anterograde identification and retrograde verification in males and females.

Outputs of the sexually dimorphic area (SDA) of the gerbil hypothalamus were identified by injecting Phaseolus vulgaris-leucoagglutinin into the medial or lateral SDA (mSDA, lSDA) in males and females. They were verified by injecting Fluoro-Gold or rhodamine-labeled beads into over half the areas that contained labeled fibers. Both anterograde and retrograde tracing showed that the mSDA and lSDA project to many of the same sites but often to differing degrees. The mSDA projects more heavily than the lSDA to many of their forebrain targets including the ventral part of the lateral septal nucleus, the bed nucleus of the stria terminalis, the medial tuberal area, and the anteroventral periventricular, arcuate, ventromedial and ventral premammillary nuclei of the hypothalamus. The lSDA projects more heavily than the mSDA to many of their mid- and hindbrain targets including the caudal, ventrolateral part of the periaqueductal gray, the retrorubral field, the pedunculopontine tegmental nucleus, and the locus coeruleus. In many other areas of the brain, the projections of the mSDA and lSDA are similar in size. These areas include the substantia innominata, the vascular organ of the lamina terminalis, the anterior amygdala, the posterior hypothalamus, the reuniens and paraventricular nuclei of the thalamus, and the pontine periaqueductal gray lateral to the fourth ventricle. The SDA pars compacta (SDApc), a small cell group embedded in the mSDA of males, projects to many fewer areas than the surrounding mSDA. It was strongly labeled when retrograde tracers were injected into the encapsulated part of the bed nucleus of the stria terminalis, the anteroventral periventricular nucleus, or the mSDA. It was also labeled from the vascular organ of the lamina terminalis, the caudal part of the lateral bed nucleus of the stria terminalis, the lSDA, the area lateral to the mSDA, the arcuate nucleus, the ventral premammillary nucleus, and the ventrolateral part of the ventromedial nucleus of the hypothalamus. Nothing resembling an SDApc was identified during retrograde tracing in females.

Afferent connections of the sexually dimorphic area of the hypothalamus of male and female gerbils.

We studied neural inputs to the sexually dimorphic area (SDA) of the gerbil hypothalamus by injecting wheat-germ agglutinin-horseradish peroxidase into its medial or lateral components in males and females. To confirm the topography of SDA afferents, we injected Phaseolus vulgaris-leucoagglutinin into areas where retrograde labeling from the medial and lateral SDA differed. Both methods indicated that the medial SDA received stronger inputs from the medial part of the bed nucleus of the stria terminalis, the ventral part of the lateral septal nucleus, the medial amygdaloid nucleus, and the amygdalohippocampal area, than the lateral SDA does. In contrast, the rostrodorsal part of the lateral septum, the lateral part of the bed nucleus of the stria terminalis, the anterior and posterior hypothalamic areas, and the dorsomedial hypothalamic nucleus project more heavily to the lateral than to the medial SDA. In addition, retrograde labeling suggested that the ventral part of the premammillary nucleus projects more strongly to the medial than to the lateral SDA, whereas the infralimbic area of the cortex and the lateral preoptic area project more strongly to the lateral than to the medial SDA. The densities of cells in the bed nucleus of the stria terminalis and medial amygdaloid nucleus that could be retrogradely labeled from the medial SDA were greater in males than in females. This was not true of labeling in the arcuate nucleus or in the ventral part of the lateral septal nucleus. Since the medial SDA receives strong inputs from areas with many steroid-accumulating cells, it could respond to steroids directly and via these afferents. In contrast, hormonal effects on the lateral SDA are more likely to occur locally.

A morphological study of the lateral olfactory areas of the telencephalon in the mongolian gerbil, Meriones unguiculatus.

This study concerns the morphological description of the nuclear groups and fiber tracts in the olfactory areas in the lateral wall of the hemisphere of the gerbil. The sense of olfaction is assumed to play an important role in the gerbil's behavior (see Vol. 15, Sect. 4). The hippocampal formation, amygdala and corpus striatum are well-developed and differentiated structures in the gerbil. These areas receive either direct or indirect olfactory connections through such pathways as the medial and lateral olfactory tracts. Other fiber tracts such as the anterior commissure, fornix, stria terminalis and the lateral forebrain bundle, carrying somatic and/or visceral fibers, as well, distribute olfactory impulses to numerous areas of the gerbil's brain. The lateral forebrain bundle (perhaps the major correlative fiber tract for olfactory, visceral and somatic impulses) begins in the striatum and terminates in the ventral thalamus and midbrain tegmentum. From there fibers are sent to the spinal cord, thereby effecting voluntary motor responses.