RESUMEN
The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG-saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Colinérgicos/farmacología , Dendritas/efectos de los fármacos , Inmunotoxinas/farmacología , Células Piramidales/ultraestructura , Corteza Visual/citología , Acetilcolinesterasa/análisis , Animales , Animales Recién Nacidos , Axones/efectos de los fármacos , Axones/enzimología , Recuento de Células , Tamaño de la Célula/efectos de los fármacos , Colina O-Acetiltransferasa/análisis , Fibras Colinérgicas/efectos de los fármacos , Fibras Colinérgicas/enzimología , N-Glicosil Hidrolasas , Prosencéfalo/citología , Prosencéfalo/efectos de los fármacos , Células Piramidales/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Proteínas Inactivadoras de Ribosomas Tipo 1 , Saporinas , Tálamo/citología , Tálamo/crecimiento & desarrollo , Corteza Visual/crecimiento & desarrolloRESUMEN
Histochemical studies show that primary sensory regions of rat cerebral cortex and dorsal thalamus display transient patterns of intense acetylcholinesterase (AChE) activity during early postnatal development. Sucrose gradient fractionation techniques were used to determine the molecular forms of AChE in developing rat brain at the time of onset (postnatal day 5), during peak expression (days 10-11), and after decline (day 18) of the transient AChE expression. Tissue from auditory and visual regions of cortex and from dorsal thalamus at each age examined contained 10S and 4S forms of AChE, similar to the pattern observed in mature brain. The 10S form was almost totally membrane bound; the 4S form was largely soluble. Hemithalamic lesions reduce both forms of AChE in cortex. These data indicate that transiently expressed AChE does not represent a unique or unusual form of the enzyme.
Asunto(s)
Acetilcolinesterasa/química , Corteza Cerebral/enzimología , Tálamo/enzimología , Animales , Corteza Auditiva/anatomía & histología , Corteza Auditiva/crecimiento & desarrollo , Corteza Auditiva/metabolismo , Centrifugación por Gradiente de Densidad , Corteza Cerebral/anatomía & histología , Corteza Cerebral/crecimiento & desarrollo , Diencéfalo/anatomía & histología , Diencéfalo/crecimiento & desarrollo , Diencéfalo/metabolismo , Histocitoquímica , Ratas , Ratas Endogámicas , Coloración y Etiquetado , Tálamo/crecimiento & desarrollo , Corteza Visual/anatomía & histología , Corteza Visual/crecimiento & desarrollo , Corteza Visual/metabolismoRESUMEN
Histochemical studies in rat dorsal thalamus demonstrate that 'non-specific' cholinesterase (ChE) enzyme activity is characteristic of neurons of the anterior dorsal (AD) and reuniens (Re) nuclei and in a cell group found as part of the central lateral (CL) and lateral dorsal (LD) nuclei. Extra-somatal ChE staining also is seen in the anterior ventral (AV) nucleus. Parallel histochemical studies in other rodents reveal slight ChE activity in neurons of the mouse AD and LD, but not in other thalamic nuclei. The dorsal thalami of hamsters, gerbils and guinea pigs show no detectable cellular staining of ChE, although low levels of extra-somatal ChE appear in AV and the internal medullary lamina. These data indicate that 'non-specific' cholinesterase activity is not found commonly in neurons of the dorsal thalamus and prominent ChE staining may be unique to the laboratory rat.