Forebrain dopamine receptors in cognitive, memory and learning processes

Neurons that utilize dopamine (DA) as a neurotransmitter have attracted great interest because of their involvement in the behavioral, endocrine and descending control of major brain functions. DA is known to exert its physiological effects on target neurons through D1-like (D1 and D5) and D2-like (D2, D3 and D4) receptor subtypes. To better understand the DA modulation of brain functions, the distribution and cellular localization of D1 and D2 DA receptors in the rat forebrain is reviewed, and their possible role in cognitive aspects of behavior is discussed. In general, DA receptors are differentially expressed and mostly distributed in different target fields of DA neurons. Both D1 and D2 receptor gene products are found in the cerebral cortex, basal ganglia and hippocampal formation, albeit in different cell groups or neuronal subpopulations, whereas D3 receptors are mainly located in limbic regions. In the cortex, mRNA signals are seen in all the areas and cortical layers except layer I. In the striatum, the most intense signal is found in the caudate-putamen, nucleus accumbens and olfactory tubercle where a large number of cells are strongly labeled for D1 and D2. In the globus pallidus only scattered D2 mRNA-containing cells are present. In contrast, no D1 or D2 messages can be seen in the ventral pallidum. In the basal forebrain, mRNA encoding the D1 receptor is detected in the islands of Calleja. The medial and lateral septal nuclei show a low D2 signal. In the amygdaloid nuclear complex, the strongest D1 receptor message is observed in the basomedial and basolateral nuclei. Conversely, the highest density of D2 mRNA-expressing cells is revealed in the central nucleus. Moderately labeled for D1 and D2 cells are scattered throughout the anterior and posterior subdivisions of the bed nucleus of stria terminalis, and within all subfields of the hippocampal formation and dentate granule cell layer. Differential regional and cellular distribution of DA receptors in the forebrain provides anatomical evidence for an area-specific regulation of the DAergic neurotransmission. It can be inferred that DA facilitates learning, memory and cognition processes via activation of both the D1 and D2 receptors.Biomedical Reviews 2005; 16: 59-75

Postnatal development of the afferent innervation of the mammalian cochlea

The adult mammalian cochlea receives dual afferent innervation: the inner hair cells (IHCs) are innervated exclusively by type I spiral ganglion neurons (SGNs), whereas the outer hair cells (OHCs) are innervated by type II SGNs. We have characterized the reorganization and morphology of this dual afferent innervation pattern as it is established in the developing rat cochlea. Before the cochlear afferent innervation reaches a mature configuration, there is an initial mismatch, where both populations of SGNs innervate both types of sensory hair cells: during the first postnatal week in the rat cochlea, type I SGN innervation is eliminated from the OHC and type II SGN innervation is eliminated from the IHC. This reorganization occurs during the first two postnatal weeks just before the onset of hearing. Our data reveal distinct phases in the development of the afferent innervation of the organ of Corti: neurite refinement, with a formation of the outer spiral bundles innervating outer hair cells; neurite retraction and synaptic pruning to eliminate type I SGN innervation of OHCs, while retaining their supply to IHCs. Such a reorganization also makes the cochlea a model system for studying CNS synapse development, plasticity and elimination. The present article summarizes the recent progress in our understanding of the afferent innervation of the cochlea.Biomedical Reviews 2012; 23: 37-52

Morphological and neurochemical plasticity of rat mesencephalic trigeminal neurons

The mesencephalic trigeminal nucleus (Me5) is a unique structure in the central nervous system (CNS), made up of pseudounipolar sensory neurons. It is also a suitable paradigm for studying the plastic alterations in neurons. It is known that the Me5 neurons utilize various neurotransmitters under normal conditions, though little information is available about the morphological and chemical events taking place in the nucleus after injury. This review provides concise description of the structural adaptive changes in Me5 neurons following peripheral axotomy of the masseteric nerve. Furthermore, it validates NADPH-diaphorase activity in them, and using immunohistochemistry for glutamate (Glu), substance P (SP), calcitonin-gene related protein (CGRP), neuropeptide tyrosine (NPY) and galanin (GAL), it deals with the altered neurochemical phenotype of the injured neurons. Our results distinctly show that the Me5 neurons in the rat are extremely sensitive to peripheral injury and we demonstrate their distinct structural and neurochemical plasticity. The adaptive morphological alterations comprise of both qualitative and quantitativealterations in the axotomized Me5 population which are statistically significant when compared with the number and phenotype of the neurons on the contralateral intact side. Besides, the axotomy-induced alterations in the neurochemical character of Me5 are best signified by the down-regulation of the classical neurotransmitters under normal conditions, and the up-regulation ofnitric oxide synthase and de novo synthesis of certain neuroactive substances such as NPY, SP, GAL and VIP. It can be inferred that the described phenomena only occur in the nucleus in cases of injury and changes in the environmental cues, and serve as adaptive mechanisms and powerful trophic factors for the neuronal survival in the Me5. There is, undoubtedly, still a long way to go in order to clarify the dynamic and plastic alterations occurring in the CNS in health and disease, and also explain their role in such important functions as pain, perception, learning, cognition and memory

Enzyme histochemical investigations of the mammalian carotid body

The carotid body (CB) in mammals is a small cluster of chemosensory and supporting cells located at the carotid bifurcation. It has been proposed that the chemoreceptor glomus cells release a variety of neurotransmitters that trigger upon hypoxia an action potential through the afferent fibers, thus conveying the chemosensory information to the central nervous system. By means of histochemical techniques the presence and distribution of certain metabolic enzymes was demonstrated in the CB of rats, guinea pigs and rabbits. In particular, we have revealed that the glomus cells expressed hydrolytic enzymes such as alkaline phosphatase (AP), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ATPase as well as oxidoreductases including oxidases like monoamine oxidase (MAO) and dehydrogenases like succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), isocitrate dehydrogenase (IDH), glucose-6-phosphate dehydrogenase (G6PD), glutamate dehydrogenase (GDH) and NADPH dehydrogenase (NADPH-diaphorase). In addition, the sustentacular cells also contained, although in a much lesser degree, AP, BChE, LDH, G6PD, GDH and NADPH-d. Some AP and SDH activity was seen in the CB microvasculature as well. Our results provide evidence that the two types of parenchymal CB cells display a different enzyme content and that the glomus cells possess enzymatic properties necessary for the secretory process. It can also be inferred that the chemoreceptor function and the nerve impulse conduction need an intensive molecular and cation exchange, and energy supply

Relation between Metopic Suture Persistence and Frontal Sinus Development

The frontal bone develops as two halves, which further unite in a single bone by the closure of the mid-sagittal metopic suture, typically by the end of the first postnatal year. The frontal sinus begins to expand into the orbital and vertical plates of the frontal bone postnatally and reaches the level of the nasion by the fourth year of age. At this time, the metopic suture is usually entirely closed. However, in the cases of failed closure of the metopic suture, its relationship to the frontal sinus development is still obscure. Here, we review the relevant literature and discuss the frontal bone development and maturation, from the viewpoint of the frontal sinus pneumatization in relation to the metopic craniosynostosis and failed closure of the metopic suture. The peculiar to the metopic skulls frontal bone configuration is rather an expression of the underlying neural mass demands than a consequence of the metopic suture persistence. Furthermore, the persistent metopic suture is frequently associated with a frontal sinus underdevelopment. It seems that the metopic suture does not inhibit the frontal sinus pneumatization itself, but rather both traits are an expression or an aftereffect of a certain condition during the early development

Morphology of the rat carotid body

The carotid body (CB) is the main peripheral arterial chemoreceptor that registers the levels of pO2, pCO2 and pH in the blood and responds to their changes by regulating breathing. It is strategically located in the bifurcation region of each common carotid artery. The organ consists of "glomera" composed of two cell types, glomus and sustentacular cells, interspersed by blood vessels and nerve bundles, and separated by connective tissue. The neuron-like glomus or type I cells contain numerous cytoplasmic organelles and dense-cored vesicles that store and release neurotransmitters. They form both conventional chemical and electrical synapses between each other and are contacted by peripheral nerve endings of petrosal ganglion afferent neurons. The glial-like sustentacular or type II cells sustain physiologic neurogenesis in the adult CB and are thus supposed to be progenitor cells. This new source of adult stem cells may be potentially useful for tissue repair after injury or for cell therapy against neurodegenerative diseases. The CB is a highly vascularized organ and its intraorgan hemodynamics possibly plays a role in the process of chemoreception. There is also evidence that chronic hypoxia induces marked morphological and neurochemical changes within the CB but the detailed molecular mechanisms by which these affect the hypoxic chemosensitivity still remain to be elucidated. Dysregulation of the CB function is implicated in various physiological and pathophysiological conditions, including ventilatory altitude acclimatization and sleep-disordered breathing. Knowledge of the morphological and functional aspects of the CB will contribute to our better understanding of respiratory homeostasis in health and disease.Biomedical Reviews 2011; 22: 41-55

Postnatal development of the inner ear efferent innervation in mammals

Efferent innervation of the inner ear is extensively studied but the whole model revealing the development of efferent synapses is not clear yet. In mammals the lateral and medial olivocochlear systems are known as the source of efferent fibers. The lateral olivocochlear system innervates the ipsilateral cochlea, terminating on the dendrites beneath the inner hair cells (IHCs), the dendrites being spiral ganglion neuron compounds. The medial olivocochlear system is involved in forming synapses directly on the outer hair cells (OHCs). To reach the final targets efferent axons use the afferent fibers as a scaffold. Efferent synaptogenesis occurs just before the onset of hearing. At P0 in rats we observed synaptic-like contacts lacking typical features. At P3 the synapses were immature. At P4-P5 efferent contacts with IHCs were clearly defined. At P6-P7 the efferent terminals were larger with distinct synaptic vesicles. During maturation, at P8-P10, the number of efferent synapses at the base of the ICHs reduced alongside with a decrease in the synaptic cisternae. After P12 efferent terminals formed axodendritic synapses below IHCs and large axosomatic synapses on OHCs. The innervation of OHCs underwent two stages, i.e. transitional with simultaneous innervation of IHCs and OHCs and a final OHC-targeted innervation. These results support the idea for a waiting period of efferent innervation before its final establishment in adult organ of Corti. We also summarize the role of neurotrophic factors, specific neurotransmitter systems, their receptors and transporters for refinement of cochlear efferent innervation.Biomedical Reviews 2013; 24: 33-48

Dopamine receptor repertoire of human granulosa cells

<p>Abstract</p> <p>Background</p> <p>High levels of dopamine (DA) were described in human ovary and recently evidence for DA receptors in granulosa and luteal cells has been provided, as well. However, neither the full repertoire of ovarian receptors for DA, nor their specific role, is established. Human granulosa cells (GCs) derived from women undergoing in vitro fertilization (IVF) are an adequate model for endocrine cells of the follicle and the corpus luteum and were therefore employed in an attempt to decipher their DA receptor repertoire and functionality.</p> <p>Methods</p> <p>Cells were obtained from patients undergoing IVF and examined using cDNA-array, RT-PCR, Western blotting and immunocytochemistry. In addition, calcium measurements (with FLUO-4) were employed. Expression of two DA receptors was also examined by in-situ hybridization in rat ovary. Effects of DA on cell viability and cell volume were studied by using an ATP assay and an electronic cell counter system.</p> <p>Results</p> <p>We found members of the two DA receptor families (D₁- and D₂ -like) associated with different signaling pathways in human GCs, namely D₁ (as expected) and D₅ (both are Gs coupled and linked to cAMP increase) and D₂, D₄ (Gi/Gq coupled and linked to IP3/DAG). D₃ was not found. The presence of the trophic hormone hCG (10 IU/ml) in the culture medium for several days did not alter mRNA (semiquantitative RT-PCR) or protein levels (immunocytochemistry/Western blotting) of D_1,2,4,5 DA receptors. Expression of prototype receptors for the two families, D₁ and D₂, was furthermore shown in rat granulosa and luteal cells by in situ hybridization. Among the DA receptors found in human GCs, D₂ expression was marked both at mRNA and protein levels and it was therefore further studied. Results of additional RT-PCR and Western blots showed two splice variants (D₂L, D₂S). Irrespective of these variants, D₂ proved to be functional, as DA raised intracellular calcium levels. This calcium mobilizing effect of DA was observed in the absence of extracellular calcium and was abolished by a D₂ blocker (L-741,626). DA treatment (48 h) of human GCs resulted in slightly, but significantly enlarged, viable cells.</p> <p>Conclusion</p> <p>A previous study showed D₂ in human GCs, which are linked to cAMP, and the present study reveals the full spectrum of DA receptors present in these endocrine cells, which also includes D₂-like receptors, linked to calcium. Ovarian DA can act thus via D_1,2,4,5, which are co-expressed by endocrine cells of the follicle and the corpus luteum and are linked to different signaling pathways. This suggests a complex role of DA in the regulation of ovarian processes.</p

A CT-study of the Cranial Suture Morphology and its Reorganization during the Obliteration

Obliteration of the cranial sutures is an age-dependent process. Its premature occurrence (craniosynostosis) causes different craniofacial deformations, dependent on the affected suture(s). The understanding of the suture morphology and the remodeling processes during the obliteration is essential for early diagnosis and treatment of the premature closure. This study aimed to investigate the morphology of open and obliterated sutures and to perform comparison analysis on the 3D images obtained by both industrial and medical computed tomography (CT) systems with various resolutions. A segment of the sagittal suture of dry skulls of known age and sex was scanned using Nikon XTH 225, an industrial CT system, developed by Nikon Metrology. The same section of the sagittal suture was observed on patients undergoing CT scanning with a multislice system Toshiba Aquilion 64 with 0.5 mm slice thickness. For 3D visualization, VGStudioMax 2.2 were used. The suture morphology was observed in coronal section on sequential 2D slices. Micro-CT (μCT) scanning of dry skulls enabled calculation of the morphometric parameters and visualization of the microarchitecture of the suture and its reorganization during the obliteration, unlike the CT imaging of patients, where the sutures were scarcely discernable. In the entirely open sections of the suture the bone edges were separated by a gap of various widths. As the obliteration proceeded, the gap gradually reduced and the bone edges got into a contact. In the fi nal stages, the traces from the contact faded away and the sutural area became a homogenous structure of increased integrity. The μCT scanning of dry bones is a powerful non-destructive technique for examination of the suture morphology. Remodeling of the suture during the obliteration leads to gradually diminishing of the gap between the bone edges to their entire coalescence