Noradrenergic projections to brainstem nuclei: Evidence for differential projections from noradrenergic subgroups

Abstract

Retrograde transport of the fluorescent tracer True Blue was used in combination with immunohistochemical staining of dopamine-beta-hydroxylase (a marker protein for noradrenergic neurons) to determine the origin of noradrenergic projections to three cranial nerve nuclei: 1) the motor nucleus of the trigeminal nerve, 2) the motor nucleus of the facial nerve, and 3) the spinal trigeminal nucleus pars interpolaris. Noradrenergic cells in the rat brainstem were divided into subgroups and their numbers were determined in serial sections stained with an antiserum to rat dopamine-beta-hydroxylase. Following tracer injections into the three brainstem nuclei, retrogradely labeled noradrenergic neurons were counted and the percentage of True Blue-labeled noradrenergic cells in each subgroup was calculated. Injections of tracer into the three cranial nerve nuclei resulted in distinctly different labeling patterns of noradrenergic cells. Of the total number of norepinephrine neurons projecting to the motor nucleus of the trigeminal nerve, 68% were observed within the A7 cell group; 75% of those innervating the motor nucleus of the facial nerve were found in the A5 cell group, and 65% of those projecting to the spinal trigeminal nucleus pars interpolaris were present in the locus ceruleus and subceruleus. These findings indicate that norepinephrine cells in the rat brainstem do not constitute a homogeneous population of cells but that several discrete systems can be identified that differ not only in topography but also in the terminal distribution of their axons. This combined retrograde transport-immunohistochemical study reveals a much higher degree of topographic order in the projections of norepinephrine neurons than has previously been recognized. The observation of differential projections of noradrenergic subgroups argues against the notion of a global influence of these cells over functionally diverse areas of the brainstem.

A5 cells are silenced when REM sleep-like signs are elicited by pontine carbachol

“…In the neonatal rat brain stem in vitro, local application of clonidine into the A5 region results in slowing of respiratory rate (15,28). Neuroanatomic studies show that descending projections of A5 cells include the dorsal horn and intermediolateral cell column in the spinal cord, ventrolateral medulla (RVLM as well as the pre-Bötzinger region containing neurons important for respiratory rhythmogenesis), NTS (a viscerosensory nucleus), and brain stem motor nuclei (1,8,9,23,26,48). However, similar to our results with clonidine microinjections, acute inhibition of cells within the A5 region with muscimol does not alter the resting arterial blood pressure or sympathetic activity in anesthetized rats (25).…”

“…11,24,25,45,46). They have extensive axonal projections that include cardiorespiratory and motor regions of the brain stem and spinal cord (1,8,9,23,36). Through these projections, they may control, among others, sympathetic and respiratory outputs and, via projection to the hypoglossal (XII) motor nucleus, may mediate noradrenergic excitation of XII motoneurons (5,22,27,40,49).…”

Conexões e caracterização neuroquímica de vias neurais envolvidas com o controle dos movimentos mandibulares

“…As marcações obtidas no tronco encefálico são semelhantes as já descritas por vários autores (Travers e Norgren, 1983;Grzanna et al, 1987;Fort et al, 1990;Turman e Chandler, 1994;Li et al, 1995;Li et al, 1996;Yasui et al, 1997;Kolta et al, 2000;Luo et al, 2001;Mascaro, 2002). Na região prosencefálica foram observadas marcações já relatadas por nós (Mascaro 2002; quando utilizamos o traçador fluorogold (FG).…”

“…Assim como vários autores (Travers e Norgren, 1983;Grzanna et al, 1987;Fort et al, 1990;Turman e Chandler,1994;Li et al, 1995;Li et al, 1996;Yasui et al, 1997;Kolta et al, 2000;Luo et al, 2001), observamos que a maior parte das projeções para o Mo5 provém dessa região, porém, observamos alguns núcleos com células retrogradamente marcadas pouco descritos . Os neurônios mesencefálicos recebem densa inervação de fibras imunorreativas a uma série de neurotransmissores e neuromediadores como a dopamina e a noradrenalina além da serotonina ), do fator liberador de corticotrofina (CRF) cujos corpos celulares parecem estar no núcleo central da amígdala (CeA) (Sakanaka et al, 1986), e da orexina (ORX) e óxido nítrico Células retrogradamente marcadas também foram verificadas, com pequena predominância ipsilateral, em núcleos da formação reticular pontina e bulbar, como no núcleo gigantocelular (Gi), núcleo gigantocelular parte alfa (GiA), além da formação reticular pontina parvicelular parte alfa (PCRtA), núcleo reticular intermediário (IRt) e mais caudalmente no núcleo do trato solitário (NTS), o que está de acordo com trabalhos realizados em ratos, gatos e coelhos Mogoseanu et al, 1993;Li et al, 1995;Li et al, 1996;Yasui et al, 1997;Kolta et al, 2000;Luo et al, 2001 Porém, o que pudemos notar foi que a maioria dos autores estava mais preocupada em estudar as marcações retrógradas no tronco encefálico do que possíveis marcações prosencefálicas.…”

“…Diversos estudos utilizando injeções de traçadores retrógrados no Mo5, em várias espécies animais foram realizados demonstrando estas aferências (Travers e Norgren, 1983;Grzanna et al, 1987;Fort et al, 1990;Turman e Chandler, 1994;Li et al, 1995;Li et al, 1996;Yasui et al, 1997;Kolta et al, 2000;Luo et al, 2001;Yamamoto et al, 2007). Porém, até o presente momento, não há consenso sobre conexões diretas entre núcleos do prosencéfalo e o Mo5, o que sugeriria que entre os mamíferos, apenas os primatas possuiriam este tipo de conexão (Travers e Norgren, 1983).…”