Apoptosis of the cerebellar neurons

Naturally occurring neuronal death (NOND) is an essential phenomenon during the course of normal development of the nervous system. Studies in vivo and on organotypic cultures have helped to elucidate the basic histological and ultrastructural features, as well as the main cellular mechanisms of NOND in several areas of the brain. This review examines the existing evidence about the two waves of apoptotic cell death that affect the different types of cerebellar neurons in normal development and certain pathological conditions. The first wave regards neuronal progenitors and pre-migratory neuroblasts, the second post-migratory neuroblasts and mature neurons. The underlying cellular and molecular mechanisms are discussed critically also in the light of their relevance to neurodegenerative diseases.     

Glucose-sensing neurons of the hypothalamus

Specialized subgroups of hypothalamic neurons exhibit specific excitatory or inhibitory electrical responses to changes in extracellular levels of glucose. Glucose-excited neurons were traditionally assumed to employ a 'beta-cell' glucose-sensing strategy, where glucose elevates cytosolic ATP, which closes KATP channels containing Kir6.2 subunits, causing depolarization and increased excitability. Recent findings indicate that although elements of this canonical model are functional in some hypothalamic cells, this pathway is not universally essential for excitation of glucose-sensing neurons by glucose. Thus glucose-induced excitation of arcuate nucleus neurons was recently reported in mice lacking Kir6.2, and no significant increases in cytosolic ATP levels could be detected in hypothalamic neurons after changes in extracellular glucose. Possible alternative glucose-sensing strategies include electrogenic glucose entry, glucose-induced release of glial lactate, and extracellular glucose receptors. Glucose-induced electrical inhibition is much less understood than excitation, and has been proposed to involve reduction in the depolarizing activity of the Na+/K+ pump, or activation of a hyperpolarizing Cl- current. Investigations of neurotransmitter identities of glucose-sensing neurons are beginning to provide detailed information about their physiological roles. In the mouse lateral hypothalamus, orexin/hypocretin neurons (which promote wakefulness, locomotor activity and foraging) are glucose-inhibited, whereas melanin-concentrating hormone neurons (which promote sleep and energy conservation) are glucose-excited. In the hypothalamic arcuate nucleus, excitatory actions of glucose on anorexigenic POMC neurons in mice have been reported, while the appetite-promoting NPY neurons may be directly inhibited by glucose. These results stress the fundamental importance of hypothalamic glucose-sensing neurons in orchestrating sleep-wake cycles, energy expenditure and feeding behaviour.     

On the origin of neurons

A report on the conference 'Neurogenesis 2007', Tokyo, Japan, 15-16 May 2007.     

Endorphinic neurons are contacting the tuberoinfundibular dopaminergic neurons in the rat brain

The anatomical relationships between endorphinic neurons and dopaminergic neurons were evaluated in the rat hypothalamus using a combination of immunocytochemistry and autoradiography. In the arcuate nucleus, endorphinic endings were seen making contacts with dopaminergic cell bodies and dendrites. No synapsis could be observed at the sites of contacts. These results strongly suggest that the endorphinic neurons are directly acting on dopaminergic neurons to modify the release of dopamine into the pituitary portal system.     

Baroreceptor sensitivity of rat supraoptic vasopressin neurons involves noncholinergic neurons in the DBB

Previous studies suggest that cholinergic neurons in the diagonal band of Broca (DBB) participate in the baroreceptor-mediated inhibition of phasic vasopressin neurons in the supraoptic nucleus (SON). To test this hypothesis, extracellular recordings were obtained from putative vasopressin SON neurons of anesthetized rats injected with the cholinergic immunotoxin 192 IgG-saporin (0.8 microg/microl) in the DBB. Baroreceptor sensitivity of neurons was tested with brief phenylephrine-induced (10 microg/10 microl iv) increases in blood pressure of at least 40 mmHg. In rats injected with vehicle or unconjugated saporin, 19 of 21 and 18 of 20 phasic neurons, respectively, were inhibited by increased blood pressure. In rats injected with 192 IgG-saporin, which significantly reduced the number of choline acetyltransferase (ChAT)-positive DBB neurons, 33 of 36 phasic neurons were inhibited. Normal rats and rats with DBB saporin injections received rhodamine bead injections into the perinuclear zone (PNZ) to retrogradely label DBB neurons, and their brains were stained for ChAT. ChAT-positive DBB neurons were not retrogradely labeled from the PNZ. Together, these results indicate that the pathway relaying baroreceptor information to the SON involves noncholinergic DBB neurons.     

Monoaminergic neurons of the mudpuppy retina

Summary The mudpuppy retina was investigated with the histofluorescence method of Falck and Hillarp in normal animals and in animals injected intraocularly with -methylnoradrenaline, 5,6-dihydroxytryptamine, or a combination of the two drugs. Catecholaminergic amacrine cells were found to form a thin layer of terminals at the border between the inner nuclear and the inner plexiform layers. Catecholaminergic interplexiform cells were not found. Indoleamine-accumulating amacrine cells were also observed. They are fifteen to twenty times more numerous than the catecholaminergic cells, and their terminals occur diffusely throughout the inner plexiform layer. In a number of eyes the majority of the indoleamine-accumulating terminals were eliminated with intraocular injections of the neurotoxin, 5,7-dihydroxytryptamine, but the reproducibility of this effect was not consistent. Intravitreal injections of 5,6-dihydroxytryptamine were used to label both types of neurons for electron microscopy. They were found to make conventional type synapses on amacrine cells and, less frequently, on bipolar cells.     

CRF-containing neurons of the rat hypothalamus

Summary The immunoreactive CRF-neurons of the rat hypothalamus have been examined immunohistochemically employing anti-rat CRF serum. These neurons are confined to the paraventricular nucleus, dorsomedial-lateral hypothalamic area, and suprachiasmatic nucleus, and are, respectively, also immunoreactive to anti-Met-enk, -alpha-MSH, and -VIP sera. Intraventricular administration of colchicine (50 g/5 l/rat) induces a dramatic enhancement of the immunostainability of the cell somata, and also accelerates the development of immunoreactivity of other stored peptides, especially in the paraventricular nucleus.The CRF-neurons respond to adrenalectomy by showing increased immunoreactivity and an increase in the number of cell bodies; in the dorsomedial-lateral area and suprachiasmatic nucleus, there is also an enhanced immunoreactivity for alpha-MSH and VIP, respectively. CRF-cells in the paraventricular nucleus become markedly hypertrophied, but do not show any enhanced immunoreactivity for Met-enk. Since the axons of the paraventricular neurons run to the median eminence, it is probable that they are involved with the endocrine control of hypophysial ACTH release. It is concluded that the CRF-containing neurons in rat hypothalamus consist of three types which are functionally and morphologically different.     

Toxicity of tunicamycin to cultured brain neurons: ultrastructure of the degenerating neurons.

Our previous study has shown that tunicamycin irreversibly downregulates the expression of GABA(A)R and causes cell death in cultured brain neurons by biochemical and light microscopic methods. In this study, we examined mechanisms underlying the degeneration of the neurons mainly employing electron microscopic analysis. Cultured neurons derived from embryonic chicken brains were incubated with 5 microg/ml of tunicamycin (TM) for 24 h, followed by continual incubation or removal of TM for additional 3 h or 24 h. Neurons treated with TM for 24 h showed dilated rough endoplasmic reticulum (rER), nuclear envelope and components of Golgi apparatus, in addition to the degranulation of rER and disaggregation of ribosomal rosettes. In neurons subjected to the prolonged incubation, some ribosomes reattached to the membranes of rER; the polyribosomes reappeared, and the swelling of Golgi apparatus subsided. However, the distention of rER persisted, and an uncommon spindle-like structure appeared in the perikarya. This structure is implicated to involve the neuronal degeneration. Moreover, extracellular cell debris was increased with time of incubation. The ratio of the light neurons, defined as containing lower cytoplasmic matrix density than the untreated control, decreased from 28% at 3 h to 3% at 24 h after the removal of TM, and 45% at further 3 h to 6% at further 24 h incubation of TM, whereas dense neurons only appeared in the two 24 h groups, as 44% and 34%. The light neurons resemble necrotic cells, but the dense neurons exhibit distinct morphological features from necrosis and apoptosis. The gel electrophoresis assay revealed the absence of DNA fragmentation in all cultures. In addition, whole cell recordings exhibited a 40% decrease of the GABA-elicited current in the neurons exposed to TM for 24 h. The results indicate irreversible toxicity of chronic TM treatment to the neurons and suggest differential mechanisms for the neuronal death among various populations of cells. It is evident that the N-glycosylation plays a critical role for neuronal survival.     

Cholinergic neurons in the hippocampus

Summary We report here on cholinergic neurons in the rat hippocampal formation that were identified by immunocytochemistry employing a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme. In general, ChAT-immunoreactive cells were rare, but were observed in all layers of the hippocampus proper and fascia dentata with a preponderance in zones adjacent to the hippocampal fissure and in the part of CA1 bordering the subiculum. All immunoreactive cells found were non-pyramidal neurons. They were relatively small with round or ovoid perikarya, which gave rise to thin spine-free dendrites. These hippocampal neurons were very similar to ChAT-immunoreactive cells in the neocortex of the same animals but were quite different from cholinergic neurons in the basal forebrain, medial septal nucleus, and neostriatum, which were larger and more intensely immunostained.Electron-microscopic analysis of ChAT-immunoreactive cells in the hippocampus and fascia dentata revealed synaptic contacts, mainly of the asymmetric type, on cell bodies and smooth proximal dendrites. The nuclei of the immunoreactive cells exhibited deep indentations, which are characteristic for non-pyramidal neurons.Our results provide evidence for an intrinsic source of the hippocampal cholinergic innervation in addition to the well-established septo-hippocampal cholinergic projection.Dr. C. Léránth is on leave of absence from the First Department of Anatomy, Semmelweis University Medical School, H-1450 Budapest, Hungary     

大脑中的抉择神经元

近年来神经科学领域的进展表明,大脑中不仅存在如位置神经元之类的特异性编码感觉信息的神经元,也存在能够特异性地反映动物思考过程的神经元。在一系列以侧内顶叶(LIP)为目标的猕猴电生理实验中,人们发现LIP神经元的动作电位发放率可以反映抉择思考的过程。抉择的研究为我们打开了一个研究大脑高级认知功能的窗口。抉择神经元的发现表明了大脑的高级认知功能是基于与感觉信息处理类似的神经计算原理。     

Location of efferent sympathetic neurons and afferent neurons in spinal ganglia innervating the heart

Location and numbers of neurons associated with sympathetic innervation of the heart within the right stellate and accessory cervical ganglia, the spinal cord, and spinal ganglia were investigated using horseradish peroxidase retrograde axonal transport techniques in cats. The enzyme was applied to central sections of the anastomosis of the stellate ganglion with the vagus nerve, the inferior cardiac nerve, and the vagosympathetic trunk caudal to the anastomosis. Labeled neurons within the stellate ganglion were located close to the point of departure of the nerves and more thinly distributed in the accessory cervical ganglion. A group of labeled cells was found in the anastomosis itself. Preganglionic neurons associated with sympathetic innervation of the heat were detected at segmental levels T₁–T₅ in the spinal cord. Labeled neurons were diffusely located in the spinal ganglia, concentrated mainly at levels T₂–T₄.Medical Institute, Ministry of Public Health of the RSFSR, Yaroslavl'. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 106–111, January–February, 1989.     

Nicotine modifies the activity of ventral tegmental area dopaminergic neurons and hippocampal GABAergic neurons

While trying to mimic the dose and time course of nicotine as it is obtained by a smoker, we found the following results. The initial arrival of even a low concentration of nicotine increased the firing rate of dopaminergic neurons from the ventral tegmental area (VTA) and increased the spontaneous vesicular release of GABA from hippocampal neurons. Longer exposure to nicotine caused variable, but dramatic, desensitization of nicotine receptors and diminished the effects of nicotine. The addictive properties of nicotine as well as its diverse effects on cognitive function could be mediated through differences in activation and desensitization of nicotinic receptors in various areas of the brain.