The subthalamic nucleus : Part II: Modelling and simulation of activity

Part II starts with a systemic model of the basal ganglia to evaluate the position of the STN in the direct, indirect and hyperdirect pathways. A summary of in vitro studies is given, describing STN spontaneous activity as well as responses to depolarizing and hyperpolarizing inputs, and high frequency stimulation. STN bursting activity and the underlying ionic mechanisms are investigated. Deep brain stimulation used for symptomatic treatment of Parkinson's disease is discussed in terms of the elements that are influenced and its hypothesized mechanisms. This part of the monograph pays attention to the pedunculopontine-subthalamic connections and tries in cell cultures to mimic neurotransmitter actions of the pedunculopontine nucleus and high frequency stiulation on cultured dissociated rat subthalamic neurons. STN cell models: single and multi compartment, and system level models are discussed in relation to subthalamic function and dysfunction. Part I and II are mutually compared

The subthalamic nucleus : Part I: Development, cytology, topography and connections

This monograph on the subthalamic nucleus accentuates in Part I the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology concerns the open nucleus concept and the neuronal types present in the STN. The cytochemistry encompasses: enzymes, NO, GRAP, calcium binding proteins, and receptors (dopamine, cannabinoid, piod, glutamate, GABA, serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic cell cord is reviewed. The topography concerns the rat, cat, baboon and human STN. The descriptions of the connections are also given from a historial point of view. Recent tracer studies on the rat nigro-subthalamic connection revealed contralateral projections

Mastication and sensibility, or the five new findings in the cat mesencephalic trigeminal nucleus

The brain even of small animals, like the rat, is complicated in its structure and its function. The hardware of the smartest personal computer is difficult to unravel. Those studying the brain know, that those brain structures that left the common evolutionary path are even harder to study. Such a structure is the mesencephalic nucleus of the trigeminal system, responsible for the sensibility of the jaw-closing muscles and the periodontium. The mesencephalic trigeminal nucleus (MTN) is a drop-like nucleus with an enormous thin tail, extending from the rostral pons along the entire caudo-rostral length of the midbrain. While all sensory ganglia of the spinal and cranial nerves are placed outside the central nervous system, the MTN, that exists of the same primary afferent neurons, is placed in the brainstem. As a consequence, this nucleus receives projections from other brain parts, projects to non-primary afferent target areas, contains a different topography and neurochemistry, in which it distinguishes itself from other primary afferent sensory ganglia of the spinal and cranial nerves. In this volume of Biomedical Reviews, the first neurochemical update on the cat MTN appears. Moreover, it stems from the Department of Anatomy, Thracian University Medical Faculty in Stara Zagora by Nikolai Lazarov and Christo Chouchkov known for their skin receptor studies and their connectivity to and in the MTN. They earned the First Dimitri Kadanoff Memorial Award truly.Biomedical Reviews 1997; 8: 21-22

The milky spots of the peritoneum and pleura: structure, development and pathology

The milky spots (MS), originally described by Ranvier as taches laiteuses, are found on the greater omentum but also in other peritoneal regions, as well as on the pleura and pericardium. They represent aggregations of mesenchymal tissue surrounding blood vessels. These small whitish regions are covered by mesothelium, and within the mesothelial layer are scattered macrophage-like cells. The blood supply of MS is provided by arterioles that give rise to capillary network formed by fenestrated or continuous endothelial cells. Most MS possess also lymphatic vessels, with extremely thin endothelial cells. The most frequent cells in MS are the macrophages, followed by lymphocytes and mast cells. Typically, the macrophages are located in the periphery, while the lymphocytes - in the center of MS. Additional structural elements are plasmocytes, adipocytes, fibroblasts, roundedfibroblast-likecells (undifferentiated mesenchymal cells), as well as collagen, reticular and elastic fibers. The nerve fibers innervating MS are located under the mesothelium and among the free cells. Despite their small size, the MS are a significantorgan, functioning at both normal and pathological conditions. Under inflammatory conditions (peritonitis), MSact as the first line of defense, and dramatically change their number, size and structure. MS are also involved in extramedullary hemopoiesis. They are the first target of intraperitoneal (intrapleural) metastases, and appear an important target in the development of immunotherapeutic strategies against malignant diseases.Biomedical Reviews 2004; 15: 47-66

Detection of phosphotyrosine, insulin receptor substrate-1 and growth factor receptor-bound protein-2 in the magnocellular forebrain system and hypothalamus of cat and man

Insulin action initiated by insulin binding to its cognate receptor is performed via phosphorylation of tyrosines on substrate proteins by the receptor tyrosine kinase domain. This process involves autophosphorylation of tyrosine residues in the cytoplasmic domain of the receptor. A comparable action is mediated by nerve growth factor (NGF) and epidermal growth factor (EGF) receptors. Few articles have been directed to the morphological regional distribution in the brain of phosphotyrosine, using antibodies. The first extensive description that proved a topographical distribution for phosphotyrosine in the rat brain was conducted by Marani and Maassen. It was shown that alternating areas positive and negative for phosphotyrosine could be described. These areas showed different localizations that were in good agreement with the biochemical results obtained by others. Moreover, fetal and postnatal series confirmed the results that phosphotyrosine content is extremely high in the developing brain as compared to the mature brain. In the mature brain, the phosphotyrosine localization is also found in the neuropil, not only in neurons. High concentrations of phosphotyrosine in a regional distribution are found in the rat rhinencephalon, the cortex, the basal ganglia (mainly in neostriatum and substantia nigra), hypothalamus and the habenular nuclei. In the hippocampus, the positivity for phosphotyrosine can be detected in the pyramidal cells and the neuropil. The hippocampal subdivisions of CA1 and CA3 can be weakly discerned. Topographical studies of the distribution of insulin receptor substrate-1 (IRS-1), growth factor receptor-bound protein-2 (GRB-2) or its adaptor molecule and substrate of insulin receptor kinase (She) that complexes to GRB-2 and conducts insulin action towards the Ras complex are absent for the brain.Biomedical Reviews 1996; 5: 73-82

Neuromelanin-containing, catecholaminergic neurons in the human brain: ontogenetic aspects, development and aging

The present review compiles data on the development and aging ofneuromelanin (NM)-containing neurons in the central nervous system. Neuromelanin is brownish-to-black pigment that accumulates in the catecholaminergic (noradrenergic and dopaminergic) neurons and is a reliable natural marker that delineates the A1-A14 catecholaminergic groups of Dahlstrom and Fuxe in the human brain. The pigmentation of noradrenergic locus ceruleus neurons starts earlier than that of dopaminergic substantia nigra, but also a considerable individual variability is present. The pigmentation is well advanced in adolescence. The data at what age the maximal pigmentation is reached are controversial, as are the data on the cell loss in the NM-containing neuronal populations by normal aging. Thus, the participation ofNM in the pathogenesis of Parkinson`s disease remains enigmatic.Biomedical Reviews 2002; 13: 39-47

Pedunculopontine tegmental nucleus. Part I: cytoarchitecture, transmitters, development and connections

The present review compiles data on the cytoarchitecture, transmitters, development, afferent and efferent connections of the pedunculopontine tegmental nucleus (PPN). PPN is a reticular formation nucleus, located in the pontomesencephalic tegmentum, closely associated with the ascending limb of the superior cerebellar peduncle. Its most typical cells are cholinergic and comprise the Ch5 neuronal group of Mesulam. It contains also glutamatergic neurons that may contain glutamate as a sole transmitter or as a co-transmitter of acetylcholine. The cholinergic neurons use also the gaseous transmitter nitric oxide, being the most prominent nitrergic neurons in the central nervous system (CNS). In aged animals, there is practically no cell loss but there are certain drastic changes in the somatodendritic morphology. PPN has an extremely rich afferent input. All basal ganglia send axons to PPN, the strongest connection being from the substantia nigra (SN), followed by pathways arising from the subthalamic nucleus (STN) and from both pallidal segments (PAL). PPN receives afferents also from the cerebral cortex, from areas of the limbic system and hypothalamus, from the cerebellum, from the brainstem - particularly serotoninergic axons from the raphe nuclei and noradrenergic axons from the locus ceruleus - as well as from the spinal cord. The efferent connections of PPN are extremely diverse, and some of them are carried out by axons that emit divergent collaterals to two different structures. The heaviest efferent pathway of PPN is destined to the thalamus, innervating virtually all thalamic nuclei, and especially the "nonspecific" intralaminar nuclei, that innervate broad ares of the cerebral cortex. All basal ganglia are innervated and in most cases the connection is bilateral. The most significant pathway innervates the dopaminergic neurons of SN, followed by a connection to STN and PAL. Other PPN efferent connections reach the cerebellum, the superior colliculus, nuclei of cranial nerves, the reticular formation, and the spinal cord. The reviewed connections of PPN suggest that it is involved significantly in the arousal systems, and is implicated in the disturbances of sleep and wakefulness. PPN is also involved in the motor functions of CNS, as well as in the movement disorders.Biomedical Reviews 2003; 14: 95-120

Age-related changes in the catecholaminergic neurons of the mesopontine tegmentum in the rat

Immunohistochemistry and computer assisted image analysis were used to examine the age-related changes in tyrosine hydroxylase- (TH-) immunoreactivity in substantia nigra (SN), ventral tegmental area (VTA), locus ceruleus (LC) and dopamine-betahyroxylase- (DBH-) immunoreactivity in LC and subceruleus nuclei of the rat. The findings in 3-month-old rats were compared with 28-month-old rats. In SN TH-positive neurons were concentrated in pars compacta and to a lesser extent - in pars lateralis. In VTA the TH-positive neurons were present over the entire area. In LC the immunoreactive perikarya were densely arranged and superimposed, but in subceruleus nuclei they were less numerous and individual cells were clearly discernible. The DBHimmunoreaction distinctly demonstrated the noradrenergic LC and subceruleus neurons. The results indicate of only subtle signs of cell loss in the dopaminergic neuronal population of SN and VTA, whilst the cell loss of the noradrenergic neurons in LC and subceruleus nuclei is evident. On the other hand, considerable age-related dendritic alterations were observed in all catecholaminergic nuclei. Cross-sectional area and optical density (OD) of the TH-immunoreactive neurons in SN, VTA and LC, and of the DBH-immunoreactive neurons in LC and subceruleus nuclei were investigated. In aging the cross-sectional area decreased statistically and OD of the neurons in SN decreased with 13%. In VTA the cross-sectional area did not change its dimensions, while the OD increased with 19%. In LC and subceruleus nuclei the cross-sectional area decreased with 36% and the OD of the neurons decreased with 16%. In conclusion, the most resistant to age-related changes catecholaminergic region in the rat is the VTA, followed by the pars compacta of SN. Rodent LC is a very vulnerable region.Biomedical Reviews 2007; 18: 45-58

Amygdala and subcortical vision: recognition of threat and fear

The amygdala (Am) is a relatively voluminous gray substance, located in the depth of the ventromedial temporal lobe. The Am has diverse afferent and efferent connections throughout the neuraxis, and is involved in the modulation of neuroendocrine functions, visceral effector mechanisms, and in complex patterns of behavior: learning and memory, aggression and defense, pain modulation, reproduction, food intake, etc. A recently revealed important function of the Am is that it acts as the brain 'lighthouse' which constantly monitors the environment for stimuli which signal a threat to the organism. The data from patients with extensive lesions of the striate cortex indicate that unseen fearful and fear-conditioned faces elicit increased Am responses. Thus, also extrageniculostriate pathways are involved. A multisynaptic pathway from the retina to the Am via the superior colliculus and several thalamic nuclei was recently suggested. We here present data based on retrograde neuronal labeling that the parabigeminal nucleus emits a substantial bilateral projection to the Am. This small cholinergic nucleus (Ch8 group) in the midbrain tegmentum is a subcortical relay visual center that is reciprocally connected with the superior colliculus. We suggest the existence of a second extrageniculostriate multisynaptic connection to Am: retina - superior colliculus - parabigeminal nucleus - Am. This pathway might be very effective since all tracts listed above are bilateral. The function of the Am by the rapid response to the sources of threat before conscious detection is significantly altered by various neuropsychiatric diseases.Biomedical Reviews 2008; 19: 1-16