Medial Division Research Articles

Preferential neurodegeneration in the cervical spinal cord of progressive supranuclear palsy

Spinal cord lesions have seldom been described in cases with progressive supranuclear palsy (PSP). We thus decided to analyze spinal cord lesions by microtubule-associated protein 2 (MAP2) immunohistochemistry in six cases of PSP, five cases of Parkinson's disease (PD) and two cases of corticobasal degeneration (CBD), all of which cause parkinsonism, while six patients without any neurological disease served as controls. In the PSP cases, the MAP2 expression in the cervical spinal cords significantly decreased in the medial division of the anterior gray horn, intermediate gray and posterior gray horn, but showed no significant change in the substantia gelatinosa and lateral division of the anterior gray horn. The thoracic and lumbar spinal cords were well preserved for MAP2 immunoreactivity. In addition, the globose type neurofibrillary tangles and glial fibrillary tangles were more conspicuous in the cervical than in the thoracic and lumbar spinal cord in PSP cases. On the other hand, the PD and CBD cases showed no significant decrease of MAP2 immunoreactivity in the spinal cords. The small neurons, which are located rather selectively in the intermediate zone of the spinal cord, are considered to be mostly present in the interneurons, and are also thought to play a role in various types of focal dystonia, such as neck dystonia. We therefore consider the distinct decrease in the MAP2-positive neuronal processes in the cervical spinal cord may partly reflect the loss of interneurons and may, thereby, possibly cause nuchal dystonia.

Do auditory responses recorded from awake animals reflect the anatomical parcellation of the auditory thalamus?

Previous studies performed in anesthetized animals have shown differences between the acoustic responses of neurons recorded from the different divisions of the medial geniculate body (MGB). This study aimed at determining whether or not such differences are also expressed when neurons are recorded from awake animals. The auditory responses of 130 neurons of the auditory thalamus were determined in awake, restrained guinea pigs while the state of vigilance of the animals was continuously monitored. There were significantly more ‘on’ phasic evoked responses and significantly fewer ‘non-responsive’ or ‘labile’ cells in the ventral division of the MGB (MGv) than in the other divisions. The response latencies and the variability of the latencies were smaller in the MGv than in the other divisions. The tuning of the neurons obtained from MGv and from the lateral part of the posterior complex were significantly sharper than those coming from the dorsal division of the MGB and the medial division. The mean threshold and the percentage of monotonic vs. non-monotonic intensity functions were not different in the subdivisions of the auditory thalamus. When compared with previous studies, the quantifications of the acoustic responses obtained in the present study gave values that differed from those reported under deep anesthesia, but were close to those reported under light anesthesia. Lastly, even if none of the physiological characteristic makes it possible, by itself, to determine the locus of recordings in the auditory thalamus, we conclude that the physiological characteristics of the evoked responses obtained in MGv differ from those of other divisions.

CART peptide-immunoreactive neurones in the nucleus accumbens in monkeys: ultrastructural analysis, colocalization studies, and synaptic interactions with dopaminergic afferents.

Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA whose level of expression was found to be increased in the striatum after acute administration of psychomotor stimulants in rats. To define better the potential role of CART peptides in behavioural and physiologic changes induced by psychomotor stimulants, we analyzed the distribution, ultrastructural features, synaptic connectivity, and transmitter content of CART peptide-immunoreactive neurones in the nucleus accumbens in monkeys. Medium-sized CART peptide-immunoreactive neurones within a rich plexus of labelled varicosities were found mostly in the medial division of the shell of the nucleus accumbens in monkeys. At the electron microscope level, CART peptide immunoreactivity was exclusively associated with neuronal structures that included perikarya, dendrites, spines as well as nerve terminals packed with electron-lucent and dense-core vesicles. Most CART peptide-containing somata displayed the ultrastructural features of striatal output neurones. The majority of labelled terminals formed symmetric axodendritic synapses and displayed gamma-aminobutyric acid (GABA) immunoreactivity. CART peptide-immunoreactive somata were not immunoreactive for parvalbumin and somatostatin, two markers of striatal interneurones, nor for calbindin D-28k, a marker of a subpopulation of projection neurones. In double-immunostained sections, CART peptide-immunoreactive dendrites were found to be contacted by tyrosine hydroxylase-positive terminals which displayed the ultrastructural features of dopamine-containing boutons. These findings strongly suggest that CART peptides may be a cotransmitter with GABA in a subpopulation of projection neurones in the monkey accumbens. Furthermore, the fact that CART peptide-immunoreactive neurones receive direct synaptic inputs from dopaminergic afferents and are particularly abundant in the caudomedial division of the shell of the nucleus accumbens suggest that CART peptides might be involved in neuronal and behavioural changes that underlie addiction to psychomotor stimulants and feeding in primates.

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.

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.

Peripeduncular lesion alters expression of c-fos induced in the female rat brain by male mounting.

In order to investigate the role of the peripeduncular nucleus (PP) in the control of lordosis in female rats, activation of neurons after mounts without intromission was investigated by means of FOS immunoreactivity (FOS-IR). Ovariectomized rats were injected with estradiol and progesterone and submitted to approximately 50 mounts by the male. The vaginal area was covered with masking tape to prevent intromission and vaginocervical stimulation. This limited stimulation produced FOS-IR in the ventrolateral division of the ventromedial hypothalamic nucleus (VMHVL), in the lateral periaqueductal grey (LPAG), in the peripeduncular nucleus (PP), and in the posterior intralaminar thalamic nucleus (PIL). No significant differences were found in the anterodorsal or posterodorsal parts of the medial amygdaloid nucleus, in the medial part of the medial preoptic nucleus, in the dorsomedial periaqueductal grey and in the medial division of the posterointermediate part of the bed nucleus of the stria terminalis. The same experiment was performed in rats with unilateral lesion of the PP. Both VMHVL and LPAG activation were significantly reduced in the ipsilateral PP lesion side, leading to the conclusion that those structures are primary targets for the somatic stimuli that trigger lordotic reflexes and which are relayed in the PP. Taking into account what is known about the function of the target structures, it is proposed that afferences relayed in the PP reaching the VMHVL would contribute to control the long range level of sexual receptivity, whereas stimuli reaching the LPAG would serve to control lordotic responses in a moment to moment fashion.

Direct synaptic connections of axons from superior colliculus with identified thalamo-amygdaloid projection neurons in the rat: Possible substrates of a subcortical visual pathway to the amygdala

The aim of the present study was to identify synaptic contacts from axons originating in the superior colliculus with thalamic neurons projecting to the lateral nucleus of the amygdala. Axons from the superior colliculus were traced with the anterograde tracers Phaseolus vulgaris leucoagglutinin or the biotinylated and fluorescent dextran amine "Miniruby." Thalamo-amygdaloid projection neurons were identified with the retrograde tracer Fluoro-Gold. Injections of Fluoro-Gold into the lateral nucleus of the amygdala labeled neurons in nuclei of the posterior thalamus which surround the medial geniculate body, viz. the suprageniculate nucleus, the medial division of the medial geniculate body, the posterior intralaminar nucleus, and the peripeduncular nucleus. Anterogradely labeled axons from the superior colliculus terminated in the same regions of the thalamus. Tecto-thalamic axons originating from superficial collicular layers were found predominantly in the suprageniculate nucleus, whereas axons from deep collicular layers were detected in equal density in all thalamic nuclei surrounding the medial geniculate body. Double-labeling experiments revealed an overlap of projection areas in the above-mentioned thalamic nuclei. Electron microscopy of areas of overlap confirmed synaptic contacts of anterogradely labeled presynaptic profiles originating in the superficial layers of the superior colliculus with retrogradely labeled postsynaptic profiles of thalamo-amygdaloid projection neurons. These connections may represent a subcortical pathway for visual information transfer to the amygdala.

Effects of Conditioning Stimulation of the Central Amygdaloid Nucleus on Tooth Pulp-Driven Neurons in the Cat Somatosensory Cortex(SI).

To study the limbic control of nociception, we examined the effect of conditioning stimulation of the central amygdaloid nucleus (ACE) on tooth pulp-driven (TPD) neurons in the first somatosensory cortex (SI). Cats were anesthetized with N(2)O-O(2) (2:1) and 0.5% halothane, and immobilized with tubocurarine chloride. The tooth pulp test stimulus was applied by a single rectangular pulse (0.5 ms in duration and 3-5 times the threshold intensity for the jaw-opening reflex). Conditioning stimuli to the ACE consisted of trains of 33 pulses (300 microA) delivered at 330 Hz at intervals of 8-10 s. In 35 out of 61 of the slow (S)-type TPD neurons with latencies of more than 20 ms, conditioning stimulation in the ACE, especially in the medial division, markedly reduced the firing response to the pulpal stimulation. The inhibition of the firing rate in the S-type neurons was 74% of the control. In these S-type neurons, the neurons that were inhibited had significantly longer latencies compared to the non-inhibited neurons (45.0 +/- 17.6 ms, n = 32 vs. 34.8 +/- 10.5 ms, n = 26). In contrast, the ACE conditioning stimulation affected only one out of 18 fast-type TPD neurons with latencies of less than 20 ms. In addition, ACE stimulation had no effect on the spontaneous discharges of either S-type or F-type neurons. The ACE inhibitory effect on S-type neurons was not diminished by naloxone administration (1 mg/kg, I.V. ), while the blockade of histamine H(1)-receptor by diphenhydramine hydrochloride (0.5 mg/kg, I.V.) partially reversed the inhibitory effect. These results suggest that the ACE inhibits ascending nociceptive information to the SI and that this inhibition is mediated in part by histamine (H(1)) receptors. It seems likely that the antinociceptive effect is a neurophysiological basis for stress-induced analgesia (SIA).

Differential projection patterns of superior and inferior collicular neurons onto posterior paralaminar nuclei of the thalamus surrounding the medial geniculate body in the rat.

The thalamic nuclei at the medial border of the medial geniculate body (i.e. the suprageniculate nucleus, the medial division of the medial geniculate nucleus, the posterior intralaminar nucleus and the peripeduncular nucleus) which relay sensory information to the amygdala are thought to receive convergent input from multiple sites. In order to delineate the organization of these multimodal thalamic nuclei, the locations of superior and inferior collicular neurons projecting to these nuclei were studied by means of retrograde transport methods. Small injections of the tracer Miniruby were made into single paralaminar thalamic nuclei. Injections of Miniruby into the suprageniculate nucleus labelled predominantly neurons in the stratum opticum of the superior colliculus, whereas injections into the medial division of the medial geniculate body, the posterior intralaminar nucleus and the peripeduncular nucleus labelled predominantly neurons in the deep layers of the superior colliculus. These injections also labelled neurons in the inferior colliculus. The majority of retrogradely labelled neurons were found in the external nucleus of the inferior colliculus and here predominantly in layer 2. Injections focused onto the medial division of the medial geniculate body additionally labelled magnocellular neurons in layer 3 of the external nucleus and a few neurons in the central nucleus. More ventrally located injections, focused onto the posterior intralaminar and peripeduncular nucleus, almost exclusively labelled neurons in layer 1 of the external nucleus and the dorsal part of the dorsal nucleus. After injections into the suprageniculate nucleus, only neurons in layer 2 were found. Neurons in the central nucleus of the inferior colliculus were only found after injections that involved the medial division of the medial geniculate body. The present results suggest that, despite a considerable degree of convergence in this thalamic region, each of these thalamic nuclei receives a unique pattern of projections from the superior and inferior colliculi. It appears that the thalamic nuclei may be concerned mainly, but not exclusively, with a single sensory modality, and give rise to parallel multimodal and unimodal pathways to the amygdala.

Projections from the lateral, basal, and accessory basal nuclei of the amygdala to the hippocampal formation in rat

The amygdaloid complex and hippocampal formation mediate functions involving emotion and memory. To investigate the connections that regulate the interactions between these regions, we injected the anterograde tracer Phaseolus vulgaris-leucoagglutinin into various divisions of the lateral, basal, and accessory basal nuclei of the rat amygdala. The heaviest projection to the entorhinal cortex originates in the medial division of the lateral nucleus which innervates layer III of the ventral intermediate and dorsal intermediate subfields. In the basal nucleus, the heaviest projection arises in the parvicellular division and terminates in layer III of the amygdalo-entorhinal transitional subfield. In the accessory basal nucleus, the parvicellular division heavily innervates layer V of the ventral intermediate subfield. The most substantial projection to the hippocampus originates in the basal nucleus. The caudomedial portion of the parvicellular division projects heavily to the stratum oriens and stratum radiatum of CA3 and CA1. The accessory basal nucleus projects to the stratum lacunosum-moleculare of CA1. The subiculum receives a substantial input from the caudomedial parvicellular division. The parasubiculum receives dense projections from the caudal portion of the medial division of the lateral nucleus, the caudomedial parvicellular division of the basal nucleus, and the parvicellular division of the accessory basal nucleus. Our data show that select nuclear divisions of the amygdala project to the entorhinal cortex, hippocampus, subiculum, and parasubiculum in segregated rather than overlapping terminal fields. These data suggest that the amygdaloid complex is in a position to modulate different stages of information processing within the hippocampal formation.

Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area

Recent studies have identified several neuropeptide systems in the hypothalamus that are critical in the regulation of body weight. The lateral hypothalamic area (LHA) has long been considered essential in regulating food intake and body weight. Two neuropeptides, melanin-concentrating hormone (MCH) and the orexins (ORX), are localized in the LHA and provide diffuse innervation of the neuraxis, including monosynaptic projections to the cerebral cortex and autonomic preganglionic neurons. Therefore, MCH and ORX neurons may regulate both cognitive and autonomic aspects of food intake and body weight regulation. The arcuate nucleus also is critical in the regulation of body weight, because it contains neurons that express leptin receptors, neuropeptide Y (NPY), alpha-melanin-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP). In this study, we examined the relationships of these peptidergic systems by using dual-label immunohistochemistry or in situ hybridization in rat, mouse, and human brains. In the normal rat, mouse, and human brain, ORX and MCH neurons make up segregated populations. In addition, we found that AgRP- and NPY-immunoreactive neurons are present in the medial division of the human arcuate nucleus, whereas alpha-MSH-immunoreactive neurons are found in the lateral arcuate nucleus. In humans, AgRP projections were widespread in the hypothalamus, but they were especially dense in the paraventricular nucleus and the perifornical area. Moreover, in both rat and human, MCH and ORX neurons receive innervation from NPY-, AgRP-, and alpha-MSH-immunoreactive fibers. Projections from populations of leptin-responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and may play a critical role in the regulation of feeding behavior and body weight.

Large-Scale Functional Connectivity in Associative Learning: Interrelations of the Rat Auditory, Visual, and Limbic Systems

Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems. J. Neurophysiol. 80: 3148-3162, 1998. Functional relations between specialized parts of the brain may be important determinants of learned behaviors. To study this, we examined the interrelations of the auditory system with several extraauditory structures in two groups of rats having different behavioral histories. Both groups were trained to associate a tone conditional stimulus (CS) with an aversive unconditional stimulus (US). For one group, a light presented with the tone predicted the absence of the US (group TL-). In the other group, the light was a neutral stimulus (group TL0). Fluorodeoxyglucose (FDG) incorporation was measured in the presence of the tone-light compound. Because the tone-light compound was physically identical for both groups, neural differences between groups reflected differences in the learned associative properties of the stimuli. Covariances of FDG uptake in the auditory system and extraauditory structures were examined using partial least squares. Three strong covariance or functional connectivity patterns were identified. The first pattern mainly reflected similarities between groups, with strong interrelations between the subcortical auditory system and the thalamocortical visual system, cerebellum, deep cerebellar nuclei, and midline thalamus. This pattern of interactions may represent part of a common circuit for relaying the associative value of the tone CS to the cerebellum and the midline thalamus. The external nucleus of the inferior colliculus and medial division of the medial geniculate nucleus were associated more strongly with this pattern for group TL-, which was interpreted as representing the change of the associative value of the tone by the light, mediated through extraauditory influences on these two regions. A second pattern involved midbrain auditory regions, superior colliculus, zona incerta, and subiculum and was stronger for group TL0. The relations between midbrain structures may represent the excitatory conditioned response (CR) evoked by the tone in this group. The final pattern was strongest in group TL- and involved interrelations of the thalamocortical auditory system with hippocampus, basolateral amygdala, and hypothalamus. This pattern may represent the learned inhibition of the CR to the tone in the presence of the light. These findings are consistent with behavioral studies suggesting that at least two types of associations are formed during associative learning. One is the sensory relation of the stimuli and another is the relation between the CS and the affective components of the US. These behavioral associations are mapped to the patterns of functional connectivity between auditory and extraauditory regions.

Differential involvement of the lateral and medial divisions of the septal area on spatial learning processes as revealed by intracranial self-administration of morphine in mice

The present study was conducted to investigate the effects of morphine self-administration into either the medial or lateral divisions of the septal region on spatial discrimination abilities in mice. To this end, BALB/c mice received a dose of 5 ng/50 nl of morphine sulfate, via a stainless steel injection cannula, inserted into either the medial septal area (MS) or the lateral septal nucleus (LS), when they are close to the end of one of the two choice arms of a Y-maze (acquisition period). In these conditions a discrimination between the reinforced arm and the neutral arm is acquired in MS as well as in LS mice. However both acquisition and subsequent extinction (vehicle only available) was more rapid in the LS group than in the MS group. Moreover, during the extinction period, numerous escape attempts from the Y-maze were observed for MS mice. When the dose of morphine was raised to 50 ng the pattern of acquisition was unchanged in the LS group. In contrast animals of the MS group learned to avoid the arm where the higher dose of morphine was delivered thus allowing us to conclude that in MS animals the drug effect became aversive at this higher dose. This possibility was directly investigated in a second experiment by closing the access to the neutral arm. Thus, for a 5-ng dose the rewarding effect of morphine was demonstrated in both MS and LS groups by the decrease of self-administration latencies which, furthermore, were notably lower than in the discrimination situation. Moreover, with the dose of 50 ng of morphine the latencies were identical for the two groups and at their lowest value thus indicating that morphine had similar appetitive effects in MS as well as in LS mice in this situation. Thus, the previously observed deficit of MS subjects, including escape attempts, disappeared when the dose of morphine was raised and the experimental context simplified. These results which demonstrate differential functional properties of these two septal divisions are discussed in terms of conflict resulting from the strongly appetitive effects of the morphine which induces, in parallel, deleterious consequences on cognitive processing in MS self-injected mice.

Connections of the dorsal zone of cat auditory cortex.

The present study examined the anatomic connections of the dorsal zone of cat auditory cortex (DZ). The DZ was discriminated physiologically from the primary auditory field (AI) on the basis of neuronal responses with long latency and broad or multipeaked tuning curves. Wheat germ agglutinin-horseradish peroxidase was then injected either by pressure or iontophoretically. The thalamocortical and corticothalamic connections of the DZ were visualized by the presence of retrogradely labeled neurons and anterogradely labeled terminal fields in the thalamus; ipsilateral corticocortical projections from other cortical fields were visualized by the presence of retrogradely labeled cells. Injections of tracer into the DZ retrogradely labeled cells mainly in the lateral division of posterior complex (Po) and in the dorsal division (MGd) of the medial geniculate body (MGB); fewer labeled cells were found in the ventral (MGv) and medial (MGm) divisions of the MGB and in the suprageniculate nucleus. The DZ projection to Po, MGv, and MGd was heavy and was more diffuse than the reciprocal thalamocortical projection; the projection to MGm was light. The corticothalamic terminations and thalamocortical cells projecting to the same part of the DZ were not superimposed rigidly. The DZ received cortical projections from AI and from the second, anterior, and posterior auditory fields, and there were strong intra-DZ connections. Together with the physiological findings, the present results suggest that the DZ is a potentially separate auditory field from AI and is likely to be involved in both temporal and spectral integration of acoustic information.

Further Evidence That the Central Nucleus of the Amygdala Is Associated with the Ethanol‐Induced Locomotor Response

The effect of ethanol on the number of Fos-like immunoreactive (Fos-li) neurons was previously studied in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains (Hitzemann and Hitzemann, Alcohol. Clin. Exp. Res. 21:1497-1507, 1997). The data obtained suggested that the locomotor activation response to ethanol found in the D2 but not the B6 strain was associated with an increase in the number of Fos-li neurons (a putative measure of synaptic activity) in the central nucleus of the amygdala (CeA), but not in other brain regions, including the basal ganglia. The current study was performed to obtain data supporting a role for the CeA in the locomotor response. B6D2 F2 intercross animals were phenotyped for their locomotor response to ethanol (1.5 g/kg). The animals from the extreme phenotypes (> 1 SD from the mean) were denoted as very high and very low activity (HH, LL) and differed in their ethanol response by >9,000 cm/15 min (baseline activity was similar in both phenotypes: 5,500 cm/15 min). These extremes especially differed from the parental strains in that the LL group showed a significant ethanol-induced inhibition of activity. After 2 weeks, HH and LL animals were rechallenged with 1.5 g/kg of ethanol or saline and the number of Fos-li neurons determined 1 hr later. In the HH group, ethanol increased the number of Fos-li neurons >600%, whereas in the LL group the increase was 170% (difference: p < 0.001). The increase in the HH group was principally located in the GABA neuron-rich lateral aspect of the CeA and not in the medial posterior-ventral division or the caps division. No significant difference was found between groups in the Fos response for the basolateral or lateral amygdala. Other brain regions were also examined, including the basal ganglia, the hippocampus (CA1, CA3, and dentate gyrus), the bed nucleus of the stria terminalis, and several cortical regions. In some regions (e.g., the bed nucleus), a significant ethanol effect was detected, but it did not differentiate the HH and LL groups. Overall, the data obtained further argue that the CeA has an important role in regulating the acute locomotor response to ethanol.

Postnatal cytoarchitecture of the rat medial geniculate body.

The medial geniculate body (MGB) is a thalamic structure that provides vital information flow to the forebrain for complex acoustic processing. The development of cytoarchitectural features of the MGB was examined in rat to identify age-related patterns of growth in major geniculate compartments that have been described previously (Clerici and Coleman [1990] J. Comp. Neurol. 297:14-31; Clerici et al. [1990] J. Comp. Neurol. 297:32-54): the ventral (MGv), dorsal (MGd), and medial (MGm) divisions. Results show that, on the day of parturition, all major nuclei of each division are characterized, including the ovoid (OV) and ventral (LV) nuclei of MGv; the dorsal, deep dorsal (DD), caudodorsal, limitans, and suprageniculate nuclei of MGd; and the MGm. The MGv and MGd, which display comparable areas at birth, show rapid growth to postnatal day 7 (PND7), which then slows until PND11, around the time of ear canal opening; subsequently, MGv accelerates growth to reach larger adult size. From PND11 to PND16, thionin facilitates parcellation by extensive staining of dendritic processes of MGd, MGm, and lateral posterior nucleus neurons but not neurons of the MGv or the dorsal lateral geniculate nucleus. Golgi stains after birth reveal restricted dendritic arborizations in MGv cells and dichotomous branching patterns of MGd neurons. Somal size in MGB increases dramatically subsequent to afferent innervation and again following onset of auditory function. Somal growth occurs between all postnatal age groups tested for OV, LV, and DD nuclei, although LV segments related to high and low frequencies do not differ. Cell packing density predicts the expanse of major MGB divisions better than somal size. These results demonstrate the integrity and growth patterns of MGB nuclei and divisions from nascence and provide a substrate for subsequent study of anatomical and physiological development of the MGB.

Evidence for a GABAergic projection from the central nucleus of the amygdala to the brainstem of the macaque monkey: a combined retrograde tracing and in situ hybridization study.

The central nucleus of the amygdala is interconnected with a variety of visceral and autonomic nuclei of the brainstem. These include the parabrachial nucleus, the nucleus of the solitary tract, the nucleus ambiguus and the dorsal motor nucleus of the vagus. Despite repeated attempts, neurochemical characterization of the major subcortical connections of the central nucleus has not yet been accomplished. Based on earlier immunohistochemical and in situ hybridization evidence indicating the presence of numerous GABAergic neurons in the macaque monkey central nucleus, we predicted that a sizeable portion of the descending projections may be GABAergic. We tested this hypothesis using a novel double labelling method with gold conjugated WGA-apoHRP as a retrograde tracer and in situ hybridization for detecting the mRNA that encodes the enzyme glutamic acid decarboxylase (GAD67) as a marker for GABAergic cells. Following WGA-apoHRP-gold injections into the brainstem, a large number of retrogradely labelled cells was observed in the medial and lateral divisions of the central nucleus. Of the retrogradely labelled cells observed in the medial division of the central nucleus, approximately half were double-labelled for GAD67 mRNA; about 30% double labelling was observed in the lateral division. These data support the view that a sizeable component of the central nucleus projection to the brainstem is GABAergic.

The Ability of Lumbar Medial Branch Blocks to Anesthetize the Zygapophysial Joint

Randomized, controlled, single blinded study. To determine the physiologic effectiveness of lumbar medial branch blocks. Zygapophysial joint pain can be diagnosed by anesthetization of the joint or its nerve supply (the medial branch divisions of the dorsal rami). The physiologic effectiveness of lumbar medial branch blocks has been assumed but not proven. Eighteen asymptomatic individuals were randomly assigned to either L4-L5 or L5-S1 zygapophysial joint injections with contrast medium until capsular distention elicited pain without extracapsular contrast spread. One week later, 15 blinded individuals underwent two randomized saline or 2% lidocaine medial branch injections that correlated to the innervation of the previously injected joint. Medical branch injections were performed such that inadvertent venous uptake was avoided in 14 individuals. Thirty minutes after medial branch injections, these 14 individuals underwent repeat capsular distention of the same zygapophysial joint provoked the prior week in an attempt to elicit another painful response. All five control individuals who received saline medial branch injections felt pain on repeat capsular distention. Nine individuals received 2% lidocaine medial branch blocks; eight felt no pain, and one felt pain on repeat capsular distention. There was a significant effect of 2% lidocaine (versus saline) medial branch injections on anesthetization of the zygapophysial joint when venous uptake was avoided during these injections. When properly performed, lumbar medial branch blocks successfully inhibit pain associated with capsular distention of the lumbar zygapophysial joints at a rate of 89%.

The fasciculus retroflexus controls the integrity of REM sleep by supporting the generation of hippocampal theta rhythm and rapid eye movements in rats

The fasciculus retroflexus (FR) fiber bundle comprises the intense cholinergic projection from the medial division of the habenula nucleus (Hbn) of the epithalamus to the interpeduncular nucleus (IPN) of the limbic midbrain. Due to the widespread connections of the Hbn and IPN, it could be surmised that the FR is integrated in the processings of various subsystems that are known to be involved in the sleep–wake mechanisms; relevant sites include the limbic forebrain and midbrain areas and more caudal pontine structures. Consequently, the present study addressed the significance of the FR in the spontaneous sleep–wake stage-associated variations of the different activity patterns of frontal cortex and hippocampal electroencephalograms (EEGs), the electrooculogram, and body movements, in freely behaving rats that had been subjected to either bilateral electrolytic lesioning of the FR or control operations. The evolution of different state combinations was assessed by the combinatory analysis of different activity stages appearing on the 6-h records. As compared to the control-operated group, the FR lesioning substantially reduced the time spent in rapid eye movement (REM) sleep by 79%, moderately decreased the duration of the intermediate state of sleep by 29%, and quiet waking state by 44%, but had virtually no effects on the durations of different types of non-REM sleep (i.e., drowsiness that which involved quiet sleep or slow-wave sleep containing delta and spindle state components) or on the times of active waking behavior that corresponded to the body movements. Quantitative decomposition analyses revealed marked variations in the frontal cortex and hippocampal activity as well as REM during the course of the extracted sleep–wake stages described and there were also some group differences. Of those individual features that were used to determine different sleep–wake stages, the overall hippocampal theta time (41% decrease) and single REM frequency (71% reduction during the REM sleep) were most affected. In contrast, the various properties of desynchronization/synchronization patterns of frontal cortex EEGs were consistently hardly influenced by the FR lesioning. Therefore, the present data suggest the involvement of the FR in the REM sleep processes by establishing prominent associations with the limbic and REM control mechanisms that involve the hippocampus and plausibly pontine ocular activity networks.

Anatomical interactions between the central amygdaloid nucleus and the hypothalamic paraventricular nucleus of the rat: a dual tract-tracing analysis

Axonal connections between the amygdala and the hypothalamic paraventricular nucleus were examined by combined anterograde-retrograde tract tracing. Iontophoretic injections of the retrograde tracer Fluorogold were placed in the paraventricular nucleus, and the anterograde tracer PHA-L in the ipsilateral central or medial amygdaloid nuclei. Single and double-label immunohistochemistry were used to detect tracers. Single label anterograde and retrograde tracing suggest limited evidence for direct connections between the central or medial amygdala and the paraventricular nucleus. In general, scattered PHA-L-positive terminals were seen in autonomic subdivisions of the paraventricular nucleus (lateral parvocellular, dorsal parvocellular and ventral medial parvocellular subnuclei) following central or medial amygdaloid nulcleus injection. Double-label studies indicate that central and medial amygdaloid nucleus efferents contact paraventricular nucleus -projecting cells in several forebrain nuclei. In the case of central nucleus injections, PHA-L positive fibers occasionally contacted Fluorogold-labeled neurons in the anteromedial, ventromedial and preoptic subnuclei of the bed nucleus of the stria terminalis. Overall, such contacts were quite rare, and did not occur in the bed nucleus of the stria terminalis regions showing greatest innervation by the central amygdaloid nucleus. In contrast, medial amygdala injections resulted in a significantly greater overlap of PHA-L labeling and Fluorogold-labeled neurons, with axosomatic appositions observed in medial divisions of the bed nucleus of the stria terminalis, anterior hypothalamic area and preoptic area. The results provide anatomical evidence that a substantial proportion of amygdaloid connections with hypophysiotrophic paraventricular nucleus neurons are likely multisynaptic, relaying in different subregions of the bed nucleus of the stria terminalis and hypothalamus.