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Thesis (Ph. D.)--University of Virginia, 2007. / Includes bibliographical references. Also available online through Digital Dissertations.

Many basal forebrain and mesopontine tegmental cholinergic projection systems tend to overlap in their origins. This raises the possibility that these projection systems are collateralized to innervate divergent areas. In experiment one, the degree to which basal forebrain and mesopontine tegmental neurons that innervate the reticular thalamic nucleus have axons that collateralize to innervate the cortex as well was examined with a retrograde fluorescence labeling method combined with immunohistochemistry. A significant portion of the labeled neurons in the region of the nucleus basalis magnocellularis and pedunculopontine tegmental nucleus projecting to the reticular thalamic nucleus were observed to be also labeled (double-labeled) following intracortical tracer injections. Many of these double-labeled neurons displayed choline acetyltransferase choline acetyltransferase immunoreactivity. It was also shown that numerous basal forebrain neurons that innervated the reticular thalamic nucleus contained the calcium-binding protein, parvalbumin. These neurons tended to be located more rostrally than the ChAT immunoreactive neurons; primarily in the region of the ventral pallidum. There was some indication that parvalbumin-containing neurons in the basal forebrain that innervate the reticular thalamic nucleus also have axons that branch to innervate the cortex. Finally, none of the basal forebrain neurons innervating the reticular thalamic nucleus was found to contain somatostatin. In experiment two, the degree to which basal forebrain neurons have axons that collateralize to innervate the interpeduncular nucleus and hippocampus was examined with retrograde fluorescence labeling methods. Labeled neurons projecting to both of these limbic structures were observed only occasionally. Comparison of the distribution of single labeled neurons innervating each of these structures revealed that within the region of origin, in the horizontal limb of the diagonal band, neurons innervating the interpeduncular nucleus tended to be located dorsally to those innervating the hippocampus. The results of these experiments are discussed in relation to their anatomical and functional implications toward a greater understanding of the basal forebrain and mesopontine cholinergic and non-cholinergic projection systems. / Medicine, Faculty of / Graduate

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 6 uppsatser.

Orientador: Fabíola Taufic Monica Iglesias / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T12:19:02Z (GMT). No. of bitstreams: 1 Gonzalez_PauloGabriel_M.pdf: 1495536 bytes, checksum: 26ccc94133bf9c2af38d1a3c267493c1 (MD5) Previous issue date: 2014 / Resumo: É bem estabelecido que a acetilcolina (ACh) produz relaxamento da musculatura lisa vascular através da liberação endotelial do óxido nítrico (NO) e, portanto, é uma das ferramentas farmacológicas mais utilizadas para avaliar a integridade do endotélio. Experimentos preliminares feito pelo nosso grupo mostraram que a ACh não relaxou a aorta e nem artéria pulmonar de sagui (Callithrix jacchus), além de induzir contração neste último leito em vaso com endotélio íntegro. Assim, o presente estudo teve como objetivo caracterizar de maneira mais detalhada a resposta colinérgica em artéria pulmonar de sagui. Em artéria pulmonar, O ADP (0.01-100 µM) produziu relaxamento dependente da concentração, que foi reduzido a aproximadamente 42% na presença do L-NAME (100 ?M) ou da indometacina (inibidor não seletivo da cicloxigenase, 10 ?M). A ACh (0.00001-1 mM) induziu contração dependente da concentração com valores de potência (pEC50) e resposta maxima (Emax) de 5.83 ± 0.08 and 90 ± 5%, respectivamente. A Emax da ACh aumentou aproximadamente 28% e 22% na presença de L-NAME e após a remoção do endotélio, respectivamente. Os antagonistas muscarínicos mais seletivos para os subtipos M2 e M3, metoctramina e 4-DAMP, e a indometacina reduziram significativamente a contração induzida pela ACh. A estimulação elétrica (4-16 Hz, 80 V, 10 segundos de estimulação) induziu contração dependente da frequência que foi significativamente reduzida na presença de 4-DAMP (0.1 µM), metoctramina (0.1 µM) e fentolamina (10 ?M) e aumentada pela fisostigmina (10 µM). Na presença de hexametônio (1 ?M), fentolamina (10 µM) ou tetrodotoxina (1 ?M) a contração mediada pela ACh não foi alterada. A análise de imunofluorescência revelou a presença da colina acetiltransferase (ChAt) na tunica media. Estes dados mostram a presença de uma inervação colinérgica excitatória em artéria pulmonar de Callithrix jacchus / Abstract: It is well established that acetylcholine (ACh) produces relaxation of vascular smooth muscle by endothelial release of nitric oxide (NO) and thus is one of the most widely used pharmacological tools to assess the integrity of the endothelium. Preliminary experiments done by our group showed that ACh did not relax the aorta and pulmonary artery of marmoset (Callithrix jacchus), and induces contraction in the latter bed in vessel with intact endothelium. Thus, the present study aimed to characterize in more detail the cholinergic response in pulmonary artery marmoset. In pulmonary artery ADP (0.01-100 µM) produced concentration-dependent relaxation which was reduced to approximately 42% in the presence of L-NAME (100 µM) and indomethacin (nonselective cyclooxygenase inhibitor, 10 µM). ACh (0.00001-1mM) produced concentration-dependent contractions with potency values (pEC50) and maximum response (Emax) of 5.83 ± 0:08 and 90 ± 5%, respectively. The Emax of ACh increased by approximately 28% and 22% in the presence of L-NAME and after removal of the endothelium, respectively. The muscarinic antagonists more selective for subtypes M2 and M3, methoctramine and 4-DAMP, and indomethacin significantly reduced ACh-induced contraction. Electrical field stimulation (EFS 4-16 Hz, 80 V, 10 seconds of stimulation) induced frequency-dependent contraction, which was significantly reduced in the presence of 4-DAMP (0.1 µM), methoctramine (0.1 µM) and phentolamine (10 µM) and augmented by physostigmine (10 µM). In the presence of hexamethonium (1 µM), phentolamine (10 µM) or tetrodotoxin (1 µM) contraction mediated by ACh was not altered. The immunofluorescence analysis revealed the expression of choline acetyltransferase (Chat) in Tunica Media. These data show the presence of an excitatory cholinergic innervation in the pulmonary artery Callithrix jacchus / Mestrado / Farmacologia / Mestre em Farmacologia

The striatum is the initial input nuclei of the basal ganglia, and it serves as an integral processing center for action selection and sensorimotor learning. Glutamatergic projections from the cortex and thalamus converge with dense dopaminergic axons from the midbrain to provide the primary inputs to the striatum. Striatal output is then relayed to downstream basal ganglia nuclei by GABAergic medium – sized spiny neurons, which comprise at least 95% of the population of neurons in the striatum. The remaining population of local circuit neurons is dedicated to regulating the activity of spiny projection neurons, and although spiny neurons form a weak lateral inhibitory network among themselves via local axon collaterals, feedforward modulation exerts more powerful control over spiny neuron excitability. Of the striatal interneurons, only one class is not GABAergic. These neurons are cholinergic and correspond to the tonically active neurons (TANs) recorded in vivo, which respond to specific environmental stimuli with a transient depression, or pause, of tonic firing. Striatal cholinergic interneurons account for less than 2 % of the striatal neuronal population, yet their axons form an extensive and complex network that permeates the entire striatum and significantly shapes striatal output by acting at numerous targets via varied receptor types. Indeed, the persistent level of ambient striatal acetylcholine as well as changes to that basal acetylcholine level underlie the major mechanisms of cholinergic signaling in the striatum, however regulation of this system by the local striatal microcircuitry is not well understood. This dissertation finds that activation of intrastriatal cholinergic fibers elicits polysynaptic GABAA inhibitory postsynaptic currents (IPSCs) in cholinergic interneurons recorded in brain slices. Excitation of striatal GABAergic neurons via nicotinic acetylcholine receptors (nAChRs) mediates this polysynaptic inhibition in a manner independent of dopamine. Moreover, activation of a single cholinergic interneuron is capable of eliciting polysynaptic GABAA IPSCs onto itself and nearby cholinergic interneurons. These findings provide an important insight into the striatal microcircuitry controlling cholinergic neuron excitability. / text

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.