Cholinergic and Nadph-δ neurons in the pedunculopontine and laterodorsal tegmental nuclei of human and nonhuman primates

The brainstem pedunculopontine (PPN) and laterodorsal tegmental (LDTg) nuclei are involved in multifarious activities, including motor control. Yet, their exact cytoarchitectural boundaries are still uncertain. We therefore initiated a comparative study of the topographical and neurochemical organization of the PPN and LDTg in cynomolgus monkeys (Macaca fascicularis) and humans. The distribution and morphological characteristics of neurons expressing choline acetyltransferase (ChAT) and/or nicotinamide adenine dinucleotide phosphate diaphorase (Nadph-δ) were documented. The number and density of the labeled neurons were obtained by stringent stereological methods, whereas their topographical distribution was reported upon corresponding magnetic resonance imaging (MRI) planes. In both human and nonhuman primates, the PPN and LDTg are populated by three neurochemically distinct types of neurons (ChAT-/Nadph-δ+, ChAT+/Nadph-δ-, and ChAT+/Nadph-δ+), which are distributed according to a complex spatial interplay. Three-dimensional reconstructions reveal that ChAT+ neurons in the PPN and LDTg form a continuum with some overlaps with pigmented neurons of the locus coeruleus, dorsally, and of the substantia nigra (SN) complex, ventrally. The ChAT+ neurons in the PPN and LDTg are —two to three times more numerous in humans than in monkeys but their density is —three to five times higher in monkeys than in humans. Neurons expressing both ChAT and Nadph-δ have a larger cell body and a longer primary dendritic arbor than singly labeled neurons. Stereological quantification reveals that 25.6% of ChAT+ neurons in the monkey PPN are devoid of Nadph-δ staining, a finding that questions the reliability of Nadph-δ as a marker for cholinergic neurons in primate brainstem.     

Expression and distribution of N-methyl-D-aspartate receptor 2A/B in anterior thalamic nuclei and hippocampus of rats

INTRODUCTION Anterior thalamic nuclei (ATN) and hippocampus are key brain re- gions concerned with learning and memory, in particular, spatial memory. Injury of ATN and hippocampus results in the dysfunction of learning and memory [1,2]. Neuroeletrophysio…     

Expression and distribution of N-methyI-D-aspartate receptor 2A/B in anterior thalamic nuclei and hippocampus of rats

BACKGROUND: Several immunohistochemical and in situ hybridization studies have demonstrated the localization of various N-methyl-D-aspartate receptors (NMDAR) subunits in certain brain regions of mammals. These studies indicate that NMDAR are widespread in mammal brains, especially in cerebral cortex and hippocampus. OBJECTIVE: To validate whether or not the NMDAR 2A/B localizes in rat anterior thalamic nuclei (ATN) and hippocampus, and observe its expression and distribution characteristics. DESIGN: Controlled study. SETTING: Department of Anatomy, College of Basic Medicine, Dalian Medical University. MATERIALS: Ten adult Sprague-Dawley rats of either gender, weighing 180-250 g, of clean grade, were provided by the Experimental Animal Center, Dalian Medical University. Rabbit polyclonal antibody to NMDAR 2A/B was the product of Chemicon Company. METHODS: This experiment was carried out in the Department of Anatomy, College of Basic Medicine, Dalian Medical University from September 2005 to May 2006. The anesthetized SD rats were transcardially perfused with 100 mL phosphate buffer solution, then perfused with paraformaldehyde through ascending aorta. After 30 minutes, their brains were harvested and post-fixed in PFA at 4 ℃ overnight. Hippocampal and anterior thalamic nuclear tissues were sliced in the coronal plane at 40 μm. The sections were stained by immunohistochemical ABC method, visualized by DAB, dehydrated routinely, performed transparence and coverslipped. Expression and distribution of NMDAR 2A/B in ATN and hippocampus of rats were observed under an optical microscope. MAIN OUTCOME MEASURES: Distribution and expression of NMDAR 2A/B in ATN and hippocampus of rats. RESULTS: NMDAR 2A/B positive neurons localized in ATN, pyramidal layer of hippocampus and granular layer of dentate gyrus in a compact and orderly pattern, and immunostained intensely. NMDAR 2A/B receptor positive neurons scattered with lower intensity of immunolabeling in other regions of hippocampus and dentate gyrus. CONCLUSION: The experimental results suggested that a large number of NMDAR 2A/B localized in ATN, pyramidal layer of hippocampus and granular layer of dentate gyrus in rats..     

Nerve cells immunoreactive for p62 in select hypothalamic and brainstem nuclei of controls and Parkinson’s disease cases

The protein p62 plays an important role in the proteasomal and/or autophagic clearance of misfolded and aggregation-prone proteins. Immunoreactivity for p62, however, not only characterizes pathological proteinaceous inclusions but also occurs in the form of homogeneous nerve cell labeling in brains of both healthy and diseased individuals, e.g., in the vagal dorsal motor nucleus and other subcortical nuclei. In sporadic Parkinson’s disease (PD), the pathological process initially involves preganglionic neurons of the parasympathetic and sympathetic system and probably advances caudo-rostrally from there along the neuroaxis. Since all subsequently affected nuclei (lower raphe nuclei, magnocellular reticular formation, locus coeruleus, and central subnucleus of the amygdala) generate descending projections that terminate in the vagal dorsal motor nucleus and intermediolateral column, it has been conjectured that retrograde axonal transport and transsynaptic transmission of a pathogen contribute to the pathogenesis of PD. The hypothalamic paraventricular nucleus also sends projections to the preganglionic nuclei under consideration and, thus, should belong to the nuclei endangered by the pathological process. However, it remains uninvolved for the duration of the disorder. For this reason, we performed a retrospective study of the relevant nuclei in a cohort of 36 individuals, including 17 with clinically documented PD, one case with incidental Lewy body disease (ILBD), and 18 controls using p62-immunocytochemistry. Remarkably, the neurosecretory cells of the paraventricular nucleus were among the sites showing homogeneous p62-immunolabeling with the greatest consistency. Its p62-immunoreactive profile may indicate that the hypothalamic paraventricular nucleus is somehow capable of effectively metabolizing misfolded proteins and/or preventing their aggregation.     

Monoaminergic activity in subregions of raphé nuclei elicited by prior stress and the neuropeptide corticotropin-releasing factor

Corticotropin-releasing factor (CRF) coordinates neuroendocrine responses to stressful stimuli; one mechanism through which CRF may modulate hypothalamic-pituitary-adrenal axis activity is via actions on neuromodulatory systems such as serotonergic systems. Recent electrophysiological studies and the distribution of CRF receptors within midbrain and pontine raphé nuclei suggest that stress and CRF may have actions on topographically organized subpopulations of serotonergic neurones. We compared the effects of vehicle or intracerebroventricular r/hCRF injections (0, 0.1, 1 or 10 micro g) in rats previously maintained in home cages or restrained for 1 h, 24 h before injection, on monoamine and monoamine metabolite tissue concentrations in the dorsal (lateral wings, rostral midline, caudal midline), median (rostral, caudal) and interfascicular raphé subdivisions of the midbrain and pontine raphé nuclei, using brain microdissection and high-performance liquid chromatography with electrochemical detection. At the lowest dose studied (0.1 micro g), CRF infusions in previously stressed rats decreased 5-hydroxytryptophan (5-HTP) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations only within the rostral median raphé nucleus. At higher doses, CRF infusions in previously stressed rats increased tissue concentrations of 5-HTP, serotonin (5-HT), or the serotonin metabolite, 5-HIAA, within rostral (but not caudal) regions of the median and dorsal raphé nuclei. By contrast, restraint stress alone had no effect on tissue concentrations of 5-HTP, 5-HT or 5-HIAA measured 24 h later in any subdivision, while CRF injections in rats not previously exposed to restraint stress, with few exceptions, also had no effect. These results suggest that the effects of CRF on serotonergic function are context-dependent, dose-dependent, and regionally specific within subdivisions of the brainstem raphé nuclei.     

Influence of interferon-gamma on the differentiation of cholinergic neurons in rat embryonic basal forebrain and septal nuclei

INTRODUCTION Recently, in the studies of the interaction between nervous system and immune system, the effect of cytokines generated by immunolog- ic cells on nervous system has attracted more and more attention from the scholars at home and abroad. These…     

Correlation between triplet repeat expansion and computed tomography measures of caudate nuclei atrophy in Huntington’s disease

Huntington’s disease (HD) is an autosomal dominant, progressive disorder characterized by choreic movements, cognitive decline, and psychiatric manifestations. Eleven patients with HD were retrospectively selected from a larger group of 42 patients based on the similar, early onset of the disease (between 21 and 30 years) and the same duration of HD at the moment of computed tomography (CT) examination (5 years). A significant correlation between the number of CAG trinucleotides and the bicaudate index or the frontal horn index, two indices of caudate atrophy, was found in this group of patients. Our results, although in a small number of patients, suggest that the striatal degeneration, assessed by CT measures, is primarily regulated by the size of expanded CAG repeats. Received: 6 November 1998 Received in revised form: 10 May 1999 Accepted: 19 June 1999     

α-Synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei

Advanced silver stains and immunohistochemical reactions against alpha-synuclein were used to detect Parkinson's disease-related cytoskeletal abnormalities in select lower brain stem nuclei. Various types of inclusion bodies including inconspicuous and heretofore unnoted granular particles and thread-like Lewy neurites were visualized. Of the nuclei investigated (gigantocellular reticular nucleus, bulbar raphe nuclei, coeruleus-subcoeruleus area), only lipofuscin- or neuromelanin-laden neuronal types showed a propensity to develop the pathological changes. Neuronal types devoid of pigment deposits remained free of the cytoskeletal abnormalities. Fine, dust-like particles and small globular Lewy bodies were encountered solely within the limits of intraneuronal lipofuscin or neuromelanin deposits.     

Oxytocin within auditory nuclei: a neuromodulatory function in sensory processing?

Oxytocin (OT) plays an important role in social bonding, ultrasonic vocalizations and other sexual behaviors in mammalian species. Although its presence within neuroendocrine regions in the forebrain is well established, its association with sensory nuclei remains unclear. We report here the presence of oxytocin immunoreactive neurons within several nuclei in the auditory brain stem of the mustached bat, Pteronotus parnellii. Immunocytochemical procedures revealed OT-immunoreactive perikarya and/or fiber terminals in restricted areas of the inferior colliculus (IC), superior olivary complex (SOC), including the medial and ventral nuclei of the trapezoid body, and in the cochlear nucleus. Perikarya were labeled predominantly in the IC and SOC and both perikarya and fiber terminals were labeled extensively in the cochlear nucleus.     

Hypoxia-ischemia in the immature rodent brain impairs serotonergic neuronal function in certain dorsal raphé nuclei

Neonatal hypoxia-ischemia(HI) results in losses of serotonergic neurons in specific dorsal raphé nuclei. However, not all serotonergic raphé neurons are lost and it is therefore important to assess the function of remaining neurons in order to understand their potential to contribute to neurological disorders in the HI-affected neonate. The main objective of this study was to determine how serotonergic neurons, remaining in the dorsal raphé nuclei after neonatal HI, respond to an external stimulus(restraint stress). On postnatal day 3(P3), male rat pups were randomly allocated to one of the following groups:(i) control + no restraint(n = 5),(ii) control + restraint(n = 6),(iii) P3 HI + no restraint(n = 5) or(iv) P3 HI + restraint(n = 7). In the two HI groups, rat pups underwent surgery to ligate the common carotid artery and were then exposed to 6% O2 for 30 minutes. Six weeks after P3 HI, on P45, rats were subjected to restraint stress for 30 minutes. Using dual immunolabeling for Fos protein, a marker for neuronal activity, and serotonin(5-hydroxytrypamine; 5-HT), numbers of Fos-positive 5-HT neurons were determined in five dorsal raphé nuclei. We found that restraint stress alone increased numbers of Fos-positive 5-HT neurons in all five dorsal raphé nuclei compared to control animals. However, following P3 HI, the number of stress-induced Fos-positive 5-HT neurons was decreased significantly in the dorsal raphé ventrolateral, interfascicular and ventral nuclei compared with control animals exposed to restraint stress. In contrast, numbers of stress-induced Fos-positive 5-HT neurons in the dorsal raphé dorsal and caudal nuclei were not affected by P3 HI. These data indicate that not only are dorsal raphé serotonergic neurons lost after neonatal HI, but also remaining dorsal raphé serotonergic neurons have reduced differential functional viability in response to an external stimulus. Procedures were approved by the University of Queensland Animal Ethics Committee(UQCCR958/08/NHMRC) on February 27, 2009.     

Amygdala, deep cerebellar nuclei and red nucleus contribute to delay eyeblink conditioning in C57BL /6 mice

That the cerebellum plays an essential role in delay eyeblink conditioning is well established in the rabbit, but not in the mouse. To elucidate the critical brain structures involved in delay eyeblink conditioning in mice, we examined the roles of the deep cerebellar nuclei (DCN), the amygdala and the red nucleus (RN) through the use of electrolytic lesions and reversible inactivation. All mice received eyeblink training of 50 trials during a daily session in the higher‐intensity conditioned stimulus (CS) condition (10 kHz, 70 dB). DCN lesions caused severe ataxia; nonetheless, the mice acquired conditioned responses (CRs). Reversible inactivation of DCN, by muscimol (MSC) injection, led to a severe CR impairment in the early sessions of conditioning; however, in later sessions, the mice acquired CRs. Amygdala lesions impaired the acquisition of CRs, which did not reach the level of sham‐operated mice, even after prolonged training sessions. MSC injections into the lateral amygdala severely impaired CRs, which began to recover after the removal of MSC. RN inactivation with MSC completely abolished CRs, and removal of MSC immediately restored CRs to the level of control mice. The results indicate that: (i) the DCN are important, but not essential, at least for the late acquisition in mouse eyeblink conditioning; (ii) the amygdala plays an important role in the acquisition and expression of CRs; and (iii) the RN is essential for the expression of CRs. Our findings reveal the various brain areas critically involved in mouse eyeblink conditioning, which include the cerebellum, amygdala and RN.     

Distributive characteristics of projection from vestibular nuclei to nucleus raphe magnus in rats

BACKGROUND: Morphological studies have confirmed that vestibular nuclei accepts serotoninergic projections from nucleus raphe magnus, nucleus raphes pallidus, etc. But it is still unclear whether there is bi-directional association between vestibular nuclei and nucleus raphe magnus. OBJECTIVE: To observe the characteristics of projective fibers from vestibular nuclei to nucleus raphe magnus using tetramethyl rhodamine (TMR) in rats, so as to provide more sufficient morphological evidence of neural association from vestibular nuclei. DESIGN: An observational experiment. SETTING: Department of Anatomy (K.K. Leung Brain Research Center), the Fourth Military Medical University of Chinese PLA. MATERIALS: Eighteen male SD rats of clean degree, weighing 250-280 g, were provided by the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA. METHODS: The experiments were carried out in the laboratory of Department of Anatomy (K.K. Leung Brain Research Center), the Fourth Military Medical University of Chinese PLA from September 2006 to January 2007. All the rats were anesthetized with intraperitoneal injection of pentobarbital sodium, then according to the coordinates on the rat brain atlas, 0.1 μL TMR (100 g/L) was injected into nucleus raphes magnus via the tip of glass microtubule by means of microinjection. Seven days later, the rats were anesthetized, then perfused and fixed to remove brain, and then frozen coronal brain sections were prepared. The retrogradely labeled neurons in the injected and projected sites were observed under fluorescence microscope. Light filters with evoked wave length of 540-553 nm and emission wave length ≥ 1 580 nm were selected to observe the orange TMR-labeled neurons. All the sections were observed and counted under the fluorescence microscope. MAIN OUTCOME MEASURES: Characteristics and number of retrogradely labeled neurons at different sites of nuclei. RESULTS: Totally 18 SD rats were enrolled, 9 of them were excluded due to the deviation of injected site, and the other 9 were involved in the final analysis of results. The concentrated region of TMR injection was mainly restricted to nucleus raphes magnus, and diffused to the surrounding area to different extents. There were obvious differences in the distributions of the labeled neurons among the subdivisions in vestibular nuclei, as well as the distributions of the labeled neurons at different sites in the same subdivision. The majority of the labeled neurons distributed in the rostral levels of medial vestibular nucleus and the lateral vestibular nucleus, while fewer labeled neurons were observed in superior vestibular nucleus. CONCLUSION: ① There might be bi-directional association between vestibular nucli and nucleus raphe magnus, suggesting that nucleus raphe magnus played a role in the transmission and processing of vestibular information. ② The projection from nucleus raphe magnus to vestibular nucleus has certain distributive characteristics in the region.     

Bigger brains or bigger nuclei? Regulating the size of auditory structures in birds

Increases in the size of the neuronal structures that mediate specific behaviors are believed to be related to enhanced computational performance. It is not clear, however, what developmental and evolutionary mechanisms mediate these changes, nor whether an increase in the size of a given neuronal population is a general mechanism to achieve enhanced computational ability. We addressed the issue of size by analyzing the variation in the relative number of cells of auditory structures in auditory specialists and generalists. We show that bird species with different auditory specializations exhibit variation in the relative size of their hindbrain auditory nuclei. In the barn owl, an auditory specialist, the hindbrain auditory nuclei involved in the computation of sound location show hyperplasia. This hyperplasia was also found in songbirds, but not in non-auditory specialists. The hyperplasia of auditory nuclei was also not seen in birds with large body weight suggesting that the total number of cells is selected for in auditory specialists. In barn owls, differences observed in the relative size of the auditory nuclei might be attributed to modifications in neurogenesis and cell death. Thus, hyperplasia of circuits used for auditory computation accompanies auditory specialization in different orders of birds.     

Influence of sex and estrous cycle on synaptic responses of the medial vestibular nuclei in rats: role of circulating 17β-estradiol

We investigated the possible influence of sex and estrous cycle on the synaptic responses of neurons in the medial vestibular nucleus (MVN) and their long-term modifications. In brain stem slices of male and female rats during proestrus (PE) and diestrus (DE), we evaluated the field potential evoked in the MVN by vestibular afferent stimulation. Here we find that in PE females the field potential had a lower threshold and higher amplitude than in DE females and in males and also that the stimulus-response curve was shifted to the left. Such difference is related to the level and cyclic fluctuation of circulating 17β-estradiol (E(2)). This is supported by the exogenous administration of E(2) in DE females and males, with low levels of circulating E(2) that enhanced the field potential amplitude to values close to those of PE females. Sex and estrous cycle also influence the MVN synaptic plasticity. This has been shown by investigating the effect of testosterone (T) on the induction of long-term effects, since T is the precursor for the neural synthesis of E(2) (estrogenic pathway), which is involved in the induction of fast long-term potentiation (LTP), or of 5α-dihydrotestosterone (DHT, androgenic pathway) which mediates slow LTP and long-term depression (LTD). We found that T mostly induced LTD in PE females and no effect in DE females, while it only provoked fast LTP in males. We suggest that high level of circulating E(2) may interfere with the conversion of T, by inhibiting the neural estrogenic pathway and facilitating the androgenic one. On the whole these results demonstrate an influence of circulating E(2) on vestibular synaptic transmission and plasticity that in some cases may contribute to the sex and menstrual cycle dependence of symptoms in human vestibular pathology.     

Vertical pendular nystagmus and hypertrophic inferior olivary nuclei degeneration: an “odd couple”

Journal of Neurology -     

Good in Bed? Power and Ethics in Psychoanalysis and Life

Abstract

In reflecting on the present moment, which involves revelations of high-profile rapists, sexual assailants, and those using their power to sexually coerce and exploit (including iconic figures Harvey Weinstein and Donald Trump), this article considers the relationship between the destructive and oppressive forces that underlie these abuses, and aspects of “ordinary” sexuality that people struggle to integrate in their relational lives. The author explores the ways that such ordinary sexuality, particularly under ubiquitous conditions of patriarchy, is likely to include aspects of objectification, coercion, and exploitation. Further considered is the psychical and relational fallout of the counteractions currently being mounted against such violations and abuses. Two brief case vignettes, one of a heterosexual man, the other of a heterosexual woman, are used as exemplars of the tolls that coercive abuses and their remedies may be taking on sexual relatedness.     

Connexins in neurons and glia：targets for intervention in disease and injury

Both neurons and glia throughout the central nervous system are organized into networks by gap junctions. Among glia, gap junctions facilitate metabolic homeostasis and intercellular communication. Amo...