Rostrocaudal Length Research Articles

Sonic hedgehog: a common signal for ventral patterning along the rostrocaudal axis of the neural tube.

The vertebrate hedgehog-related gene, sonic hedgehog, is expressed in ventral domains along the entire rostrocaudal length of the neural tube, including the forebrain. Shh induces the differentiation of ventral neuronal cell types in explants derived from prospective forebrain regions of the neural plate. Neurons induced in explants derived from diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein Islet-1, but these neurons possess distinct identities that match those of the ventral neurons normally generated in these two subdivisions of the forebrain. These results, together with other studies of neuronal differentiation at caudal levels of the neural tube, suggest that a single inducing molecule, Shh, mediates the induction of distinct ventral neuronal cell types along the entire rostrocaudal extent of the embryonic central nervous system.

Quantitative, Morphological, and Somatotopic Nuclear Changes after Facial Nerve Regeneration in Adult Rats

The anatomic reorganization of the subnucleus that controls the stylohyoid muscle (the stylohyoid subnucleus) within the brain stem facial nucleus was studied after regeneration of the facial nerve in adult rats. Horseradish peroxidase was injected into the right stylohyoid muscle 3 to 21 months after transection and repair of the right facial nerve at the level of the stylomastoid foramen. Position, number, and soma diameter of retrogradely horseradish peroxidase-labeled motoneurons were established, as well as the rostro-caudal extension of the stylohyoid subnucleus. In experimental rats, the stylohyoid subnucleus showed either an ipsilateral (50% of the rats) or a bilateral representation. In all of the experimental rats, the motoneurons composing the stylohyoid subnucleus had a more dispersed horizontal distribution pattern when compared with controls. More than 80% of the motoneurons were located outside the borders of the normal stylohyoid subnucleus, either ventrally or, especially in the rostral sections, dorsally closer to the floor of the fourth ventricle. The mean rostro-caudal length of the stylohyoid subnucleus was 2028.6 +/- 152.7 microns. The mean motoneuron number was 481.4 +/- 109.5 (2.20-fold greater than control values), and the motoneuron diameter distribution ranged from 7 to 43 microns. This study demonstrates that after regeneration of the facial nerve in adult rats, major changes occur in both the location and number of motoneurons that make up the stylohyoid subnucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Sonic hedgehog induces the differentiation of ventral forebrain neurons: A common signal for ventral patterning within the neural tube

The vertebrate hedgehog-related gene Sonic hedge-hog (Shh) is expressed in ventral domains along the entire rostrocaudal length of the neural tube, including the forebrain. We show here that SHH induces the differentiation of ventral neuronal cell types in explants derived from prospective forebrain regions of the neural plate. Neurons induced in explants derived from both diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein lsl-1, and these neurons possess distinct identities that match those of the ventral neurons generated in these two subdivisions of the forebrain in vivo. A single inducing molecule, SHH, therefore appears to mediate the induction of distinct ventral neuronal cell types along the entire rostrocaudal extent of the embryonic central nervous system.

Initial Axial Level-Dependent Differences in Size of Avian Dorsal Root Ganglia Are Imposed by the Sclerotome

We have recently shown that there is very early variation in dorsal root ganglia (DRG) size based on their axial position. From the time of their condensation at Stage (St.) 20 (Embryonic Day 3), before the onset of apoptosis, the ganglia in brachial segments 14 and 15 are more than 80% larger on the average than those in cervical 5 and 6. This difference in volume is due to increased numbers of cells in the brachial DRG. In addition, the rostrocaudal length was found to be significantly greater for brachial ganglia, and the greater length of the brachial ganglia was found to be correlated with a greater length of brachial than cervical sclerotomes. It was therefore proposed that the difference in DRG size at the time of gangliogenesis is likely to arise from colonization by a larger initial number of neural crest cells of the longer adjacent rostral sclerotomes in brachial somites. In the present work, we have performed two types of experiments to test this hypothesis. First, we have performed heterotopic grafts of segmental plate mesoderm from cervical to brachial levels and vice versa. In all of these grafts, the sclerotomes developed with a rostrocaudal extent (length) corresponding to their level of origin in the donor embryo. DRG that formed in the grafted mesoderm attained a length appropriate to that of ganglia developing in segments of the axial level of the donor mesoderm, not that of the host. Second, we have estimated proliferation of DRG cells at St. 20 using HNK-1/bromodeoxyuridine double-stain immunocytochemistry. The percentage of cells in S-phase at both brachial and cervical levels of the neuraxis in newly formed ganglia was observed to be the same. These two lines of evidence strongly argue that the initial difference in size between DRG at different axial levels is not intrinsic, but rather is imposed by the mesodermal microenvironment in which they develop, as is the case for DRG segmentation. This is in contrast to what may occur in the hindbrain, where determination of rhombomere identity and neural crest segmentation are thought to be intrisic to the nervous system.

Subcompartmental organization of the ventral (protrusor) compartment in the hypoglossal nucleus of the rat

The extent and myotopic organization of the ventral (protrusor) compartment of the hypoglossal nucleus (nXII) in the rat is controversial. Of particular concern is the location of motoneurons that innervate the intrinsic (verticalis, transversus) as compared to extrinsic (genioglossus) tongue protrusor muscles. These issues were investigated with retrograde transport, lesion/degeneration/immunocytochemical, and classic Golgi staining techniques. Results from these experiments demonstrate the following: (1) the ventral compartment extends the entire rostrocaudal length of nXII and is organized into three longitudinally oriented subcompartments, one medial and one lateral within the boundaries of nXII, and one outside the confines of nXII, defined as the lateral accessory subcompartment; 2) the medial and lateral subcompartments contain motoneurons that innervate the intrinsic (verticalis, transversus) and extrinsic (genioglossus) tongue protrusor muscles, respectively, while the lateral accessory subcompartment innervates the geniohyoid muscle; (3) ventral subcompartments are unequal in size and vary along the rostrocaudal dimension of nXII. The medial subcompartment is largest caudally and smallest rostrally, while the converse is true for the lateral subcompartment. By contrast, the lateral accessory subcompartment is present only along the caudal one-half of nXII; (4) medial and lateral subcompartments are further organized into smaller subgroups. Medial and centromedial subgroups are discernible within the medial subcompartment, lateral and centrolateral subgroups within the lateral subcompartment. Both medial and lateral subgroups extend throughout the rostrocaudal length of nXII, whereas the centromedial and centrolateral subgroups are present only along the middle two-thirds of nXII where they form a central motoneuron band; (5) there is an inverse myotopic organization within the medial and lateral subcompartments such that proximal and distal portions of intrinsic and extrinsic protrusor muscles receive innervation from rostral and caudal motoneurons, respectively; and (6) there is a correlation between motoneuron morphology (size, shape and dendritic field domains), subcompartment localization, and myotopic specificity. Motoneurons in the medial subcompartment are small (mean = 23.08 microns), round to globular, with dendrites oriented medially, dorsomedially, dorsolaterally, and caudally, whereas lateral subcompartment motoneurons are large (mean = 29.49 microns), round to triangular, with dendrites directed mainly mediolaterally and dorsally. These data are relevant to understanding the functional organization of nXII and the motor control of the tongue. Results are further discussed relative to the convergence of multifunctional afferent systems in the ventromedial subcompartment of nXII.

The Axonal Arborization of Single Thalamic Reticular Neurons in the Somatosensory Thalamus of the Rat

This study describes the axonal projections of single neurons of the thalamic reticular complex within the somatosensory thalamic nuclei in rats. Experiments were performed under urethane anaesthesia and reticular cells were labelled by extracellular microiontophoretic applications of biocytin. The axonal arborization of 25 thalamic reticular cells projecting to the ventrobasal (VB) nucleus and/or to the posterior thalamic (Po) complex were reconstructed from serial horizontal sections. Reticular cells labelled with biocytin display somatodendritic features similar to those reported previously. Their cell body is fusiform and their dendrites bear few spines and show a high degree of streaming along the horizontal curved axis of the nucleus. In most cells, axon-like beaded processes stem out from dendrites but, contrary to previous descriptions, no intrareticular axonal collateral was observed. The axonal arborization of most thalamic reticular cells is confined within the limits of a single thalamic nucleus; only two neurons were seen projecting to both the VB and the Po nuclei. In VB, termination fields form short rods (diameter approximately 150 microns, length approximately 200-300 microns) densely packed with grape-like boutons and varicosities; termination fields in Pro are larger, much less dense, and they are contained within a horizontal slab of tissue (thickness approximately 200 microns, mediolateral width approximately 400 microns, rostrocaudal length approximately 1 mm. By charting the position of all labelled cells within the thickness of the thalamic reticular complex, a strip-like arrangement was revealed. Cells projecting to Po occupy the innermost portion of the nucleus whereas those projecting to the ventral-posteromedial and ventral-posterolateral nuclei are located respectively in the middle and in the outer tiers of the nucleus. This strip-like reciprocity was confirmed by separate biocytin injections performed in VB and in Po. These results show that inhibition of reticular origin is distributed within the rat dorsal thalamus in a highly specific manner, most likely according to a principle of reciprocity within the somatotopic representation of the body.

Intergeniculate leaflet: An anatomically and functionally distinct subdivision of the lateral geniculate complex

The intergeniculate leaflet (IGL) in the rat is a distinctive subdivision of the lateral geniculate complex that participates in the regulation of circadian function through its projections to the circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. The present investigation was undertaken to provide a precise definition of the IGL and a characterization of its neuronal organization including neuronal morphology, chemical phenotype, connections, and synaptic organization. The IGL extends the entire rostrocaudal length of the geniculate complex and contains a distinct population of small to medium neurons. In Golgi preparations, the neurons are multipolar with dendrites largely confined to the IGL. The neurons can be subdivided into three groups on the basis of neurotransmitter content and projections: (1) neurons that contain GABA and neuropeptide Y and project to the SCN; (2) neurons that contain GABA and enkephalin and project to the contralateral IGL; and (3) a small group of neurons that projects to the SCN but not characterized as yet by neurotransmitter content. The IGL receives dense, bilateral input from retinal ganglion cells and dense substance P input of unknown origin. A number of neurons in the anterior hypothalamic area and, particularly, the retrochiasmatic area project to the IGL, and there are sparse projections from brainstem monoamine and cholinergic neurons. The synaptic organization of the IGL is complex with afferents terminating in glomerular complexes that include axoaxonic synaptic interactions. Virtually all IGL afferents synapse upon dendrites and spines, with the densest synaptic input occurring on the distal portions of the dendritic arbor. The organization of the IGL and its connections as revealed in this analysis is in accord with its role in the integration of visual input with other information to provide feedback regulation of the SCN pacemaker.

Stable vasopressin innervation in the degenerating human locus coeruleus in Alzheimer's disease

The vasopressin (VP) innervation of the human locus coeruleus (LC) was immunocytochemically investigated in Alzheimer's disease (AD) patients and non-demented controls. A dense innervation of VP fibers was present throughout the entire rostro-caudal length of the LC in both, controls and AD-patients. The VP immunoreactivity was confined to fibers; no signs of cell body staining could be found. Comparison of five non-demented control subjects anf five AD patients on fifteen different levels throughout the LC revealed that the VP innervation of this nucleus remained intact in AD, even in the rostral part of the LC, which is the most affected region with respect to neuronal loss.

Axial level‐dependent differences in size of avian dorsal root ganglia are present from gangliogenesis

Dorsal root ganglia (DRG) form from neural crest cells that colonize the rostral sclerotomies of the somites of the trunk of higher vertebrates. Differences in sensory field size and innervation density are reflected by the size of the ganglia at different axial levels. Some of the position-dependent differences in ganglionic size derives from asymmetry in embryonic programmed cell death, when more DRG neurons die at non-limb-innervating levels than at the levels that innervate the limbs. I have now examined early chick embryos to determine whether there is asymmetry in DRG size at the time of their condensation at stage 20 [embryonic day (E) 3], before the onset of cell death. Ganglia in brachial segments 14 and 15 are more than 80% larger on average than those in cervical segments 5 and 6 at this stage of development. This difference in volume is due to increased numbers of cells in the brachial sensory ganglia. Several other morphometric parameters of the DRG and sclerotomies were then determined. The rostro-caudal length was found to be significantly greater for brachial ganglia. The greater length of the brachial ganglia was found to be correlated with (1) a greater length of brachial than cervical sclerotomies and (2) the occupation by brachial ganglia of a larger proportion of the rostro-caudal extent of the sclerotome. These results demonstrate that the mature pattern of axial differences in ganglionic size are foreshadowed by a pattern set during the period of gangliogenesis, which is then further sculpted by apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Innervation of the feline eyelids.

The innervation of the eyelids is incompletely understood. This is a particular problem for those who wish to develop animal models of eyelid dysfunction in humans. Blepharospasm, for example, is a disease of uncontrolled eyelid spasm that is difficult to manage clinically because the aetiology is not understood. The anatomical literature on eyelid innervation is sparse and even conflicting. We attempted to study eyelid innervation, both sensory and motor, with injection of horseradish peroxidase (HRP) into the superior eyelid, inferior eyelid, and bulbar conjunctiva. We used 13 anesthetized weanling cats. Shape and structure of the facial nucleus varied along its rostrocaudal extent, but there was a clear demarcation of lateral and medial division. HRP-filled facial nucleus cells were ipsilateral to the injection site, and label appeared throughout the rostrocaudal length. All injection sites, including bulbar conjunctiva, labelled facial nucleus neurons located with overlapping distribution, predominantly in the dorsal part of the lateral division. Likewise, heavy labelling occurred throughout the entire ipsilateral cranial cervical ganglion and the trigeminal ganglion in all kittens. Injection of upper or lower eyelids caused some labelling in the second through the fourth cervical spinal ganglia.

A unique neuronal organization in the cat pretectum revealed by antibodies to the calcium-binding protein calbindin-D 28K

The pretectum is an important center for visual reflexes. However, the location, boundaries, and connections of individual nuclei of the pretectum are incompletely understood. In cat, the traditionally defined nuclear boundaries have been placed in doubt by recent evidence showing that the retinal input to the pretectum forms four continuous projection zones that do not match the cytoarchitectural boundaries of individual pretectal nuclei defined by previous studies. We now show that antibodies to the calcium-binding protein calbindin-D 28K (CaBP) label clusters of neurons within the pretectum that match the zones of retinal termination. Four obvious cell clusters within the pretectum were labeled by CaBP antisera. Computer three-dimensional reconstruction of these cell clusters revealed that they form four distinct but continuous zones that run the rostrocaudal length of the pretectum in a medial-to-lateral direction. By combining anterograde HRP labeling of retinal terminals with CaBP immunocytochemistry, these CaBP-labeled cell clusters were found virtually to overlap the retinal projection zones. The CaBP-labeled neurons included both multipolar and fusiform morphologies, and most were medium- to large-sized cells. HRP retrograde transport studies showed that many CaBP-labeled neurons in the clusters projected to the LGN, while none projected to the inferior olive (IO). GABA-immunoreactive neurons were also found within the CaBP cell clusters, but these neurons were smaller than most CaBP-labeled neurons, and none were retrogradely labeled following HRP injections into the LGN or IO. Two-color antibody double-labeling experiments did not reveal any GABA neurons within the clusters that colocalized CaBP. In summary, calbindin is a precise marker of neuron clusters that overlap the retinal projection zones in the cat pretectum. Many of these CaBP neurons project to the LGN, and none contain GABA.

Somatosensory response properties of contralaterally projecting spinothalamic and nonspinothalamic neurons in the second cervical segment of the cat

1. The upper cervical spinal cord contains over one-third of the cells of the spinothalamic tract (STT). This study investigated response properties of contralaterally projecting STT neurons in C2 of the cat by the use of single-unit, microelectrode recordings. Standard antidromic stimulation and collision techniques were used to identify STT units projecting to the contralateral thalamus. Once an STT unit was found, its receptive field (RF) and responses to cutaneous stimuli such as touch, pressure, deep muscle squeeze, tap, noxious pinch, and heat were characterized. C2 units that were not activated from the contralateral thalamus (non-STT units) were also characterized. The locations of thalamic stimulation electrodes and spinal recording sites were reconstructed from electrolytic lesions. 2. A total of 48 STT and 68 non-STT units were well characterized. RF sizes were classified as small, intermediate, large, or whole body. Each unit was also classified as having one of two possible response types: simple units were those with homogeneous responses within the RF and were classified as low threshold (LT), high threshold (HT), wide dynamic range (WDR), deep, or tap. Complex units were those that responded differently in different regions of the RF. 3. The average depth of non-STT units subdivided by RF size was 2.1 +/- 0.6 (SD) mm for cells with small RFs, 2.4 +/- 0.8 mm for cells with intermediate RFs, 2.8 +/- 0.3 mm for cells with large RFs, and 2.7 +/- 0.5 mm for cells with whole-body RFs. The average depth of non-STT units based on response type was 2.0 +/- 0.5 mm for LT, 2.3 +/- 0.7 mm for HT, 2.1 +/- 0.7 mm for WDR, 2.6 +/- 0.9 mm for deep, 2.6 +/- 0.5 mm for tap, and 2.4 +/- 0.2 mm for complex. 4. A somatotopic organization along the rostrocaudal length of C2 and upper C3 was observed for non-STT units with small- and intermediate-size RFs. The average distance of the recording sites from the rostralmost dorsal rootlet of C2 was 3.8 +/- 2.1 mm for units with RFs on the face, 7.1 +/- 4.3 mm for units with RFs on the neck, and 11.9 +/- 5.1 mm for units with RFs on the forelimb. 5. The average threshold for antidromic activation of STT units was 175 +/- 120 microA. Most C2 STT units were activated from the ventroposterior region of the thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Columnar organisation of the inferior olive projection to the posterior lobe of the rat cerebellum

The organisation of the olivocerebellar projection to lobules VI, VIII, and IX of the posterior lobe of the rat cerebellum was investigated in detail by using the retrograde tracer wheat germ agglutinin-horseradish peroxidase. Small, well-defined rostro-caudally orientated columns of olive cells were found to project to different parasagittal areas in the posterior lobe. A column of olive cells about 2,000 microns in rostro-caudal length in subnucleus "c" and nucleus beta of the caudal medial accessory olive (MAO) provides climbing fibre input to the most medial part of lobules VI and IX, but this projection is displaced laterally in lobule VIII by a projection from a column of cells about 600 microns in rostro-caudal length in lateral caudal MAO (subnucleus "a"). It is possible that each of these columns of olivary neurones may be further subdivided in the rostro-caudal axis so that different sections project to different medio-lateral parts of the cortex. A fine-grain 'sublobular' localisation may also exist: the projection to midline lobule VIc arises at caudal levels of the olive from a band of cells in the transition region between subnucleus "c" and nucleus beta, whilst by comparison the projection from caudal levels of the olive to lobules VIa and VIb arises from cells located more ventrally in nucleus beta. Evidence is also presented to confirm that the posterior lobe vermis in the rat extends further laterally than in other mammals and that part of it receives a projection from a column of olive cells, 1,000 microns in rostro-caudal length, in a newly defined region of caudal MAO, termed subnucleus "b1."

Studies of the brain structures involved in diffuse noxious inhibitory controls: the mesencephalon

1. Diffuse noxious inhibitory controls (DNIC) were compared in control sham-operated rats and in rats with lesions of mesencephalic structures involved in the modulation of pain, namely the periaqueductal gray (PAG), cuneiformis nucleus (CNF), and parabrachial nucleus (PB). 2. Lesions were induced by ibotenic acid: 4 micrograms (0.2 microliter) injected bilaterally in the PAG or the CNF-PB area or 10 micrograms (0.5 microliter) injected unilaterally in the CNF or PB. Control animals were microinjected with the vehicle (artificial CSF) alone. Histological controls were performed at the end of each electrophysiological experiment. Only the animals in which the target structure (PAG, CNF, or PB) was completely destroyed in its entire rostrocaudal length were selected. With the exception of the cell bodies of the trigeminal mesencephalic nucleus, all neurons were destroyed in these regions. 3. At least 1 wk after the microinjection procedure, recordings were made from convergent neurons in both the right and left trigeminal nucleus caudalis. These neurons were activated by both noxious and nonnoxious stimuli applied to their excitatory receptive fields and gave responses due to activation of both A- and C-fibers after percutaneous electrical stimulation of their receptive fields. These types of response were inhibited by applying noxious conditioning stimuli to heterotopic areas of the body, namely immersing a paw in a 50 degrees C water bath. A virtually total block of the responses was observed during the application of the noxious conditioning stimulus, and this was followed by long-lasting poststimulus effects. 4. The general properties of neurons (sizes of receptive fields, spontaneous activity, thresholds to obtain C-fiber-evoked responses, responses to C-fiber activation) were all found to be similar in the control and the lesioned animals. The percentage inhibition of the C-fiber-evoked responses of the trigeminal convergent neurons elicited by the noxious conditioning stimuli were found to not be significantly different in any group of animals; in all the animals, inhibitions exceeded 85% during the immersion of either paw and were followed by long-lasting poststimulus effects. 5. We conclude that the PAG, CNF, and PB, three structures that are putatively involved in the modulation of pain, do not participate directly in the supraspinal part of the loop subserving DNIC. The involvement of other structure(s) and a possible indirect modulation of DNIC are discussed. It is also concluded that the PAG, CNF, and PB do not participate directly in the tonic descending inhibitory controls, which are presumed to modulate the activity of convergent neurons.

Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression

The present study provides qualitative and quantitative investigations of the norepinephrine (NE) neurons in the locus coeruleus (LC) in two neurodegenerative disorders, the senile dementia of the Alzheimer type (SDAT) and Parkinson's disease (PD). The group of PD subjects was subdivided into cases without dementia (P - D), cases with dementia, L-dopa responsive (P + D), and cases with fulminant dementia whose motor disorder symptoms were L-dopa nonresponsive (P + D/L-dopa non-responsive). NE neurons were demonstrated by immunocytochemistry against tyrosine hydroxylase (TH). Quantitations of neuronal parameters and cell numbers and three-dimensional reconstructions of the LC were carried out with a computer-assisted system. In SDAT cases, the rostrocaudal LC length (13 +/- 2.2 mm) is shorter than in controls (14.9 +/- 1.4 mm). The four basic LC neuron classes found in the normal human brain (large multipolar, large "bipolar," small multipolar, and small "bipolar" neurons; Chan-Palay and Asan: J. Comp. Neurol. this issue) are recognizable, but many cell somata are swollen and misshapen with fore-shortened, thick, and less branched dendrites. LC neuron numbers are reduced (between -3.5% and -87.5%). Neuron loss is greatest in the rostral part, less in the middle, and least in the caudal part. In PD cases, the rostrocaudal length (12.4 +/- 1.5 mm) is shorter than in SDAT and controls. The neuronal morphology is more severely altered than in SDAT. The basic neuron classes are hardly distinguishable. Most cell bodies are swollen; they frequently contain Lewy bodies; and the dendrites are short and thin with absent or reduced arborizations. Neuron numbers are more reduced than in SDAT (between -26.4% and -94.4%). Alterations are as severe caudally as rostrally in P - D, and P + D/L-dopa nonresponsive cases. P + D cases are more severely affected rostrally. The presence of depression in SDAT and Parkinson's patients is accompanied by the greatest loss of LC neurons. On the basis of morphological alterations of the TH-immunoreactive neurons, and the degree and topographical distribution of neuron loss, a differentiation is possible between the LC in normal brain and that in SDAT and PD for diagnostic purposes.

Quantitation of catecholamine neurons in the locus coeruleus in human brains of normal young and older adults and in depression

A quantitative study of the morphology and distribution of norepinephrinergic neurons in the human locus coeruleus (LC) is given for normal young and older adult brain. Norepinephrine (NE)-producing neurons are identified by immunocytochemistry of two NE biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), visualized by the peroxidase-antiperoxidase and immunogold-silver-staining methods. TH and DBH immunoreactions yield equivalent results. Both immunocytochemical visualization methods allow detailed analysis of neuronal morphology. The neurons of the human LC fall into four classes: large multipolar neurons with round or multiangular somata, large elliptical "bipolar" neurons, small multipolar neurons, and small ovoid "bipolar" neurons. Though most of the neurons contain neuromelanin pigment, some larger neurons lack pigmentation. Dendritic arborization of all neurons is extensive. Computer-assisted quantitative measurements of the parameters somatic size, dendritic arbor length, surface area, and volume are given. Somatic areas of LC neurons of all four classes are decreased in older adult brain, but dendritic arborization is equally extensive as in the younger. The rostrocaudal length of the LC is approximately 15 mm, and no age-dependent decrease is observed. Computer-assisted mapping of immunoreactive neurons and three-dimensional reconstruction allow division of the LC into rostral, middle, and caudal parts with characteristic distribution of neurons. Small neurons predominate in all parts, but the relative contribution of larger cells decreases in a rostrocaudal direction. A cell loss of 27-37% occurs in older adult brains and to 55% in the brain of a chronically depressed patient without dementia. Cell loss is highest in the rostral part, lower in the middle, and absent in the caudal part, and more small cells are lost than larger ones.

Intrinsic connections within and between cochlear nucleus subdivisions in cat.

The cat cochlear nuclear complex (CNC) is divided into three major subdivisions: the anteroventral, the posteroventral, and the dorsal cochlear nuclei (AVCN, PVCN, and DCN, respectively). Each of these subdivisions receives a topographic projection from the cochlea and each consists of a number of different cell types. The interconnections between these subdivisions and the cell types which give rise to them were studied by means of small injections of horseradish peroxidase (HRP) made at physiologically identified locations. DCN injections resulted in few labeled cells in the DCN, suggesting that its internal connections are very limited. In contrast, these same DCN injections resulted in numerous labeled cells in the PVCN and AVCN. Labeled PVCN cells, consisting of multipolar, octopus, and small spindle-shaped cells, were located in spatially restricted laminae stretching the entire rostrocaudal length of the nucleus, while labeled AVCN cells consisting of multipolar, globular, small spindle-shaped and small spherical cells were broadly distributed over the posterior half of the nucleus. Similar injections placed in the PVCN resulted in numerous labeled cells in all three subdivisions. The PVCN and AVCN cells labeled after PVCN injections were widely distributed across the isofrequency representations in both nuclei, while the labeled DCN cells were restricted to locations over the injection sites. Injections placed in the posterior half of the AVCN resulted in only very few labeled cells in the DCN. No cells were labeled following injections in the rostral AVCN.

Intrinsic organization of the rat cutaneus trunci motor nucleus.

1. We have investigated how the organization of the cutaneus trunci muscle (CTM) motor nucleus might correspond to the pattern of its physiological activation (see accompanying report, 61) by using HRP to label retrogradely the motoneurons supplying different anatomically and physiologically defined muscle compartments. The CTM motoneuron pool was found to be comprised of a tightly packed column of ventrolaterally located cells extending from caudal C6 to rostral T1 and to contain 1,183 cells per side; this unusually large number of motoneurons is consistent with the precisely localized reflex behavior exhibited by the muscle. 2. Each of three major motor nerves that functionally divide the CTM into three major longitudinal muscle fields (dorsal, lateral, ventral) was found to derive from a distinct subcolumn of motoneurons, which extends for the full rostrocaudal length of the parent CTM motor nucleus, such that the dorsal motor nerves derive from a medially located subcolumn, the lateral motor nerves from a centrally located subcolumn, and the ventral motor nerves from a subcolumn of motoneurons that sits most laterally in the CTM motor nucleus. 3. Localized injections of HRP into different rostrocaudal regions of the muscle revealed a further subdivision of the CTM motor nucleus: motoneurons located rostrally in the motoneuron pool supplied the rostral regions of the muscle, whereas more caudally located motoneurons in the pool supplied progressively more caudal sites in the muscle. 4. These results reveal the existence of both a mediolateral and a rostrocaudal subdivision of the motor nucleus; thus this intrinsic spatial organization of motoneurons relates the CTM motor nucleus topographically to the body coordinates of its target, the muscle. The possible relation of these findings to the expression of local sign in the CTM reflex, and how the underlying circuitry could develop appropriately, is discussed.

Topography of nerve cell loss from the locus caeruleus in middle aged persons with Down's syndrome

A topographical analysis of nerve cell loss from the locus caeruleus in middle aged patients with Down's syndrome (whose brains show the pathological changes of Alzheimer's disease), has shown that cell loss is confined to dorsal areas, being least most rostrally and greatest caudally. By contrast, there is no significant cell loss from ventral parts of the locus, at any point along its rostrocaudal length. Dorsally located neurones of the locus project to cerebral cortex; ventrally located neurones to non-cortical areas such as basal ganglia, cerebellum and spinal cord. These data suggest that the damage to nerve cells of the locus caeruleus in Down's syndrome at middle age, like that seen in Alzheimer's disease itself, relates to primary pathological events within the cortical projection fields of affected cells with perikaryal loss following on as a later change.

Localization of glutamate, glutaminase, aspartate and aspartate aminotransferase in the rat midbrain periaqueductal gray.

Glutamate and aspartate are putative excitatory neurotransmitters in the central nervous system. The present study utilized novel monoclonal antibodies against fixative-modified glutamate and aspartate and polyclonal antisera against the amino acid synthesizing enzymes, glutaminase and aspartate aminotransferase, to analyze the distribution of these amino acids in the rodent midbrain periaqueductal gray. Glutamate-, aspartate-, glutaminase- and aspartate aminotransferase-like immunoreactive neurons, fibers and processes are present throughout the rostrocaudal length of the periaqueductal gray. Glutamate- and glutaminase-like immunoreactive neurons displayed a similar homogeneous pattern of distribution, being localized predominantly to the lateral and dorsal subdivisions of the periaqueductal gray. Co-localization experiments suggest that glutamate and glutaminase are in fact co-contained within the same PAG neurons. Aspartate aminotransferase-like immunoreactive neurons were distributed in a pattern similar to glutamate and glutaminase with the exception that fewer cells were stained in the dorsocaudal and the rostral third of the PAG. Aspartate-like immunoreactive neurons were less numerous than glutamate-like immunoreactive cells and were located in the lateral aspect of the PAG. These results demonstrate a specific and distinct distribution of glutamate and aspartate immunoreactive neurons and support recent data suggesting that glutamate and aspartate serve as excitatory neurotransmitters in the PAG.