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1.
PLoS Biol ; 15(9): e2001283, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28934203

RESUMO

Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.


Assuntos
Hormônios Esteroides Gonadais/fisiologia , Comportamento Sexual Animal/fisiologia , Maturidade Sexual , Córtex Somatossensorial/crescimento & desenvolvimento , Vias Aferentes/crescimento & desenvolvimento , Animais , Feminino , Masculino , Distribuição Aleatória , Ratos Wistar , Tálamo/crescimento & desenvolvimento , Útero/crescimento & desenvolvimento
2.
J Comp Neurol ; 521(11): 2585-601, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23322443

RESUMO

Somesthesis-guided exploration of the external world requires cortical processing of both cutaneous and proprioceptive information and their integration into motor commands to guide further haptic movement. In the past, attention has been given mostly to the cortical circuits processing cutaneous information for somatic motor integration. By comparison, little has been examined about how cortical circuits are organized for higher order proprioceptive processing. Using the rat cortex as a model, we characterized the intrinsic and corticocortical circuits arising in the major proprioceptive region of the primary somatosensory cortex (SI) that is conventionally referred to as the dysgranular zone (DSZ). We made small injections of biotinylated dextran amine (BDA) as an anterograde tracer in various parts of the DSZ, revealing three distinct principles of its cortical circuit organization. First, its intrinsic circuits extend mainly along the major axis of DSZ to organize multiple patches of interconnections. Second, the central and peripheral regions of DSZ produce differential patterns of intra-areal and corticocortical circuits. Third, the projection fields of DSZ encompass only selective regions of the second somatic (SII), posterior parietal (PPC), and primary motor (MI) cortices. These projection fields are at least partially separated from those of SI cutaneous areas. We hypothesize, based on these observations, that the cortical circuits of DSZ facilitate a modular integration of proprioceptive information along its major axis and disseminate this information to only selective parts of higher order somatic and MI cortices in parallel with cutaneous information.


Assuntos
Vias Aferentes/anatomia & histologia , Vias Aferentes/fisiologia , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Propriocepção/fisiologia , Córtex Somatossensorial/anatomia & histologia , Córtex Somatossensorial/fisiologia , Vias Aferentes/crescimento & desenvolvimento , Animais , Biotina/análogos & derivados , Córtex Cerebral/crescimento & desenvolvimento , Interpretação Estatística de Dados , Dextranos , Feminino , Imuno-Histoquímica , Córtex Motor/fisiologia , Perfusão , Fito-Hemaglutininas , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/crescimento & desenvolvimento , Vibrissas/inervação , Vibrissas/fisiologia
3.
J Clin Invest ; 121(4): 1608-23, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21383497

RESUMO

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type (AMPA-type) glutamate receptors (AMPARs) play an important role in plasticity at central synapses. Although there is anatomical evidence for AMPAR expression in the peripheral nervous system, the functional role of such receptors in vivo is not clear. To address this issue, we generated mice specifically lacking either of the key AMPAR subunits, GluA1 or GluA2, in peripheral, pain-sensing neurons (nociceptors), while preserving expression of these subunits in the central nervous system. Nociceptor-specific deletion of GluA1 led to disruption of calcium permeability and reduced capsaicin-evoked activation of nociceptors. Deletion of GluA1, but not GluA2, led to reduced mechanical hypersensitivity and sensitization in models of chronic inflammatory pain and arthritis. Further analysis revealed that GluA1-containing AMPARs regulated the responses of nociceptors to painful stimuli in inflamed tissues and controlled the excitatory drive from the periphery into the spinal cord. Consequently, peripherally applied AMPAR antagonists alleviated inflammatory pain by specifically blocking calcium-permeable AMPARs, without affecting physiological pain or eliciting central side effects. These findings indicate an important pathophysiological role for calcium-permeable AMPARs in nociceptors and may have therapeutic implications for the treatment chronic inflammatory pain states.


Assuntos
Inflamação/fisiopatologia , Nociceptores/fisiologia , Dor/fisiopatologia , Receptores de AMPA/fisiologia , Vias Aferentes/crescimento & desenvolvimento , Vias Aferentes/fisiopatologia , Animais , Artrite Experimental/fisiopatologia , Benzodiazepinas/farmacologia , Cálcio/metabolismo , Gânglios Espinais/crescimento & desenvolvimento , Gânglios Espinais/fisiopatologia , Inflamação/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Dor/tratamento farmacológico , Permeabilidade , Receptores de AMPA/antagonistas & inibidores , Receptores de AMPA/deficiência , Receptores de AMPA/genética , Transmissão Sináptica
4.
J Neurosci ; 29(9): 2762-7, 2009 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-19261871

RESUMO

Auditory perception in vertebrates depends on transduction of sound into neural signals in the inner ear hair cells (HCs) and on transmission of these signals to the brain through auditory (VIIIth) nerve afferents. To investigate the developmental acquisition of auditory inputs by the CNS, we have electrophysiologically and morphologically examined the process of acquisition of auditory responsiveness by zebrafish macular HCs and the Mauthner cells (M-cells) in vivo. The M-cells are a paired large reticulospinal neurons in the hindbrain; they receive direct inputs from the VIIIth nerve afferents and initiate an acoustic startle response. Whole-cell recordings from the M-cells showed that sound-evoked postsynaptic currents were first observed around 40 h postfertilization (hpf); during subsequent development, onset latency decreased and amplitude increased. The appearance and development of microphonic potentials in the inner ear coincided with those of the acoustic responses of the M-cell, whereas the functional auditory circuits from the macular HCs to the M-cell were already formed at 27 hpf. These results suggest that the functional maturation of inner ear after formation of the auditory pathway is a critical process in the acquisition of auditory inputs by CNS neurons.


Assuntos
Vias Aferentes/crescimento & desenvolvimento , Vias Auditivas/crescimento & desenvolvimento , Sistema Nervoso Central/crescimento & desenvolvimento , Orelha Interna/crescimento & desenvolvimento , Peixe-Zebra/fisiologia , Estimulação Acústica , Animais , Animais Geneticamente Modificados , Potenciais Microfônicos da Cóclea/fisiologia , Eletrofisiologia , Potenciais Evocados Auditivos/fisiologia , Imuno-Histoquímica , Neurônios/fisiologia , Nervo Vestibulococlear/crescimento & desenvolvimento
5.
Brain Res ; 1173: 66-77, 2007 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-17850770

RESUMO

The central nucleus of the inferior colliculus (IC) is a laminated structure that receives multiple converging afferent projections. These projections terminate in a layered arrangement and are aligned with dendritic arbors of the predominant disc-shaped neurons, forming fibrodendritic laminae. Within this structural framework, inputs terminate in a precise manner, establishing a mosaic of partially overlapping domains that likely define functional compartments. Although several of these patterned inputs have been described in the adult, relatively little is known about their organization prior to hearing onset. The present study used the lipophilic carbocyanine dyes DiI and DiD to examine the ipsilateral and contralateral projections from the lateral superior olivary (LSO) nucleus to the IC in a developmental series of paraformaldehyde-fixed kitten tissue. By birth, the crossed and uncrossed projections had reached the IC and were distributed across the frequency axis of the central nucleus. At this earliest postnatal stage, projections already exhibited a characteristic banded arrangement similar to that described in the adult. The heaviest terminal fields of the two inputs were always complementary in nature, with the ipsilateral input appearing slightly denser. This early arrangement of interdigitating ipsilateral and contralateral LSO axonal bands that occupy adjacent sublayers supports the idea that the initial establishment of this highly organized mosaic of inputs that defines distinct synaptic domains within the IC occurs largely in the absence of auditory experience. Potential developmental mechanisms that may shape these highly ordered inputs prior to hearing onset are discussed.


Assuntos
Colículos Inferiores/anatomia & histologia , Colículos Inferiores/crescimento & desenvolvimento , Núcleo Olivar/anatomia & histologia , Núcleo Olivar/crescimento & desenvolvimento , Vias Aferentes/anatomia & histologia , Vias Aferentes/crescimento & desenvolvimento , Fatores Etários , Aminoácidos/farmacocinética , Animais , Animais Recém-Nascidos , Carbocianinas/farmacocinética , Gatos
6.
J Comp Neurol ; 485(4): 280-92, 2005 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-15803506

RESUMO

Development of whisker-specific neural patterns in the rodent somatosensory system requires NMDA receptor (NMDAR)-mediated activity. In cortex-specific NR1 knockout (CxNR1KO) mice, while thalamocortical afferents (TCAs) develop rudimentary whisker-specific patterns in the primary somatosensory (barrel) cortex, layer IV cells do not develop barrels or orient their dendrites towards TCAs. To determine the role of postsynaptic NMDARs in presynaptic afferent development and patterning in the barrel cortex, we examined the single TCA arbors in CxNR1KO mice between postnatal days (P) 1-7. Sparsely branched TCAs invade the cortical plate on P1 in CxNR1KO mice as in control mice. In control animals, TCAs progressively elaborate patchy terminals, mostly restricted to layer IV. In CxNR1KO mice, TCAs develop far more extensive arbors between P3-7. Their lateral extent is twice that of controls from P3 onwards. By P7, CxNR1KO TCAs have significantly fewer branch points and terminal endings in layers IV and VI but more in layers II/III and V than control mouse TCAs. Within expansive terminal arbors, CxNR1KO TCAs develop focal terminal densities in layer IV, corresponding to the rudimentary whisker-specific patches. Given that thalamic NMDARs are spared in CxNR1KO mice, the present results show that postsynaptic NMDARs play an important role in refinement of presynaptic afferent arbors and whisker-specific patterning in the developing barrel cortex.


Assuntos
Axônios/metabolismo , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Receptores de N-Metil-D-Aspartato/deficiência , Tálamo/crescimento & desenvolvimento , Tálamo/metabolismo , Vias Aferentes/crescimento & desenvolvimento , Vias Aferentes/metabolismo , Animais , Animais Recém-Nascidos , Córtex Cerebral/citologia , Camundongos , Camundongos Knockout , Receptores de N-Metil-D-Aspartato/genética , Tálamo/citologia
7.
Folia Morphol (Warsz) ; 62(2): 129-32, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12866673

RESUMO

A comparative quantitative study of the somatosensory thalamocortical connections in the rat and rabbit, labeled with the fluorescent retrograde tracer Fluoro-Gold (FG), was conducted by means of unbiased stereology. FG was injected into the primary somatosensory cortex of the rat and rabbit in different age groups from P0 to P180 (P-postnatal day). The numerical density of retrogradely labeled the ventroposterolateral (VPL) projection neurons was analyzed. A significant decrease in this parameter was observed during the first two weeks of postnatal life in both studied species. Changes of the neuropil volume and selective elimination of early cortical connections stemming from the VPL may possibly cause this process. A withdrawal of axon collaterals from the expanded cortical sites as well as apoptosis (existing both in the VPL and parietal cortex) contribute to a decrease in the numerical density. Our observations allow us to conclude that the thalamocortical somatosensory connections established before the birth undergo significant quantitative changes in both studied species during the first two weeks of postnatal life and this period seems to be crucial for maturation of the thalamocortical loop.


Assuntos
Vias Aferentes/crescimento & desenvolvimento , Córtex Somatossensorial/crescimento & desenvolvimento , Estilbamidinas , Tálamo/crescimento & desenvolvimento , Vias Aferentes/metabolismo , Animais , Animais Recém-Nascidos , Apoptose , Transporte Axonal/fisiologia , Contagem de Células , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/análise , Neurônios/citologia , Neurônios/metabolismo , Coelhos , Ratos , Ratos Wistar , Córtex Somatossensorial/citologia , Córtex Somatossensorial/metabolismo , Especificidade da Espécie , Coloração e Rotulagem , Tálamo/citologia , Tálamo/metabolismo
8.
J Comp Neurol ; 457(4): 345-60, 2003 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-12561075

RESUMO

The homeobox transcription factors Emx1 and Emx2 are expressed in overlapping patterns that include cortical progenitors in the dorsal telencephalic neuroepithelium. We have addressed cooperation of Emx1 and Emx2 in cortical development by comparing phenotypes in Emx1; Emx2 double mutant mice with wild-type and Emx1 and Emx2 single mutants. Emx double mutant cortex is greatly reduced compared with wild types and Emx single mutants; the hippocampus and dentate gyrus are absent, and growth and lamination of the olfactory bulbs are defective. Cell proliferation and death are relatively normal early in cortical neurogenesis, suggesting that hypoplasia of the double mutant cortex is primarily due to earlier patterning defects. Expression of cortical markers persists in the reduced double mutant neocortex, but the laminar patterns exhibited are less sharp than normal, consistent with deficient cytoarchitecture, probably due in part to reduced numbers of preplate and Reelin-positive Cajal-Retzius neurons. Subplate neurons also exhibit abnormal differentiation in double mutants. Cortical efferent axons fail to exit the double mutant cortex, and TCAs pass through the striatum and approach the cortex but do not enter it. This TCA pathfinding defect appears to be non-cell autonomous and supports the hypothesis that cortical efferents are required scaffolds to guide TCAs into cortex. In double mutants, some TCAs fail to turn into ventral telencephalon and take an aberrant ventral trajectory; this pathfinding defect correlates with an Emx2 expression domain in ventral telencephalon. The more severe phenotypes in Emx double mutants suggest that Emx1 and Emx2 cooperate to regulate multiple features of cortical development.


Assuntos
Vias Aferentes/patologia , Córtex Cerebral/patologia , Proteínas de Homeodomínio , Neurônios/patologia , Bulbo Olfatório/patologia , Tálamo/patologia , Vias Aferentes/crescimento & desenvolvimento , Animais , Axônios/patologia , Morte Celular , Diferenciação Celular , Córtex Cerebral/crescimento & desenvolvimento , Vias Eferentes/crescimento & desenvolvimento , Vias Eferentes/patologia , Desenvolvimento Embrionário e Fetal , Regulação da Expressão Gênica no Desenvolvimento , Hipocampo/crescimento & desenvolvimento , Hipocampo/patologia , Proteínas de Homeodomínio/genética , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Mutantes , Mutação , Bulbo Olfatório/crescimento & desenvolvimento , Fenótipo , Proteína Reelina , Tálamo/crescimento & desenvolvimento , Fatores de Transcrição/genética
9.
Mol Cell Neurosci ; 21(3): 477-92, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12498788

RESUMO

N-Methyl-D-aspartate receptors (NMDARs) are important for synaptic refinement during development. In CxNR1KO mice, cortical excitatory neurons lack NR1, the essential subunit of the NMDAR, and in their primary somatosensory (S1) cortex whisker-specific cellular patterns, "barrels," are absent. Despite this cytoarchitectural defect, thalamocortical axons (TCAs) representing the mystacial vibrissae form topographically organized patterns and undergo critical period plasticity. This region-specific knockout mouse model allows for dissection of the mechanisms underlying patterning of the pre- and postsynaptic neural elements in the S1 cortex. In the absence of functional NMDARs, layer IV cell numbers are unaltered, but these cells fail to segregate into barrels. Furthermore, the dendritic fields of spiny stellate cells do not orient toward TCA terminal patches as in normal mice. Instead, they radiate in all directions covering larger territories, exhibiting profuse branching with increased spine density. Comparison of TCA patches with serotonin transporter (5-HTT) immunohistochemistry or Dil labeling also indicates that in the CxNR1KO cortex TCAs form smaller patches and individual axon terminal branching is not as well developed as in control cortex. Our results suggest that postsynaptic NMDAR activation is critical in communicating periphery-related sensory patterns from TCAs to barrel cells. When postsynaptic NMDAR function is disrupted, layer IV spiny stellate cells remain imperceptive to patterning of their presynaptic inputs and elaborate exuberant dendritic specializations.


Assuntos
Vias Aferentes/crescimento & desenvolvimento , Diferenciação Celular/genética , Interneurônios/metabolismo , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Terminações Pré-Sinápticas/metabolismo , Receptores de N-Metil-D-Aspartato/deficiência , Córtex Somatossensorial/crescimento & desenvolvimento , Transmissão Sináptica/genética , Vias Aferentes/citologia , Vias Aferentes/metabolismo , Animais , Animais Recém-Nascidos , Padronização Corporal/genética , Proteínas de Transporte/metabolismo , Polaridade Celular/genética , Dendritos/metabolismo , Dendritos/ultraestrutura , Feminino , Imunofluorescência , Regulação da Expressão Gênica no Desenvolvimento/genética , Interneurônios/citologia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Terminações Pré-Sinápticas/ultraestrutura , Receptores de N-Metil-D-Aspartato/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina , Transdução de Sinais/genética , Córtex Somatossensorial/citologia , Córtex Somatossensorial/metabolismo , Tálamo/citologia , Tálamo/crescimento & desenvolvimento , Tálamo/metabolismo
10.
Eur J Neurosci ; 15(7): 1115-24, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11982623

RESUMO

In the neostriatum, the proenkephalin gene is expressed in medium spiny GABA neurons, which project to the globus pallidus. The expression is activated by glutamatergic projections from the neocortex via NMDA receptors. In these experiments we have used slice cultures of rat neostriatum to study the role of GABA in proenkephalin gene expression. Our results show that GABA is released from neostriatal neurons and negatively regulates the proenkephalin gene expression induced by NMDA receptor stimulation. The GABAA receptors involved seem to be colocalized with NMDA receptors on the projection neurons, which express the proenkephalin gene. In further experiments, we have found that the proenkephalin gene expression is not only activated by neocortical projection neurons but also by intrinsic striatal neurons as well as by projections from the thalamus. All these glutamatergic afferents enhance the proenkephalin gene expression via NMDA receptors. Their efficacy is regulated by endogenous GABA.


Assuntos
Encefalinas/genética , Expressão Gênica/fisiologia , Interneurônios/metabolismo , Neostriado/metabolismo , Inibição Neural/fisiologia , Precursores de Proteínas/genética , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismo , Vias Aferentes/citologia , Vias Aferentes/crescimento & desenvolvimento , Vias Aferentes/metabolismo , Animais , Animais Recém-Nascidos , Vias Eferentes/citologia , Vias Eferentes/crescimento & desenvolvimento , Vias Eferentes/metabolismo , Antagonistas de Aminoácidos Excitatórios , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Agonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-A , Expressão Gênica/efeitos dos fármacos , Interneurônios/citologia , Interneurônios/efeitos dos fármacos , Neocórtex/citologia , Neocórtex/crescimento & desenvolvimento , Neocórtex/metabolismo , Neostriado/citologia , Neostriado/crescimento & desenvolvimento , Inibição Neural/efeitos dos fármacos , Técnicas de Cultura de Órgãos , RNA Mensageiro/metabolismo , Ratos , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Tálamo/citologia , Tálamo/crescimento & desenvolvimento , Tálamo/metabolismo
11.
J Neurosci Res ; 65(6): 595-603, 2001 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-11550228

RESUMO

Using an anti-Tn monoclonal antibody, the Tn antigen was detected immunohistochemically in prenatal and early postnatal central nervous tissues. On embryonic day 9 (E9), the antigen was distributed throughout the single neuroepithelial layer in the neocortex and then became more prominent in the preplate than in the ventricular zone along with formation of the preplate. Following division of the preplate and concomitant formation of the cortical plate, distinct labeling of the neocortex occurred in the marginal, subplate and intermediate zones, whereas in the cortical plate and ventricular zone were virtually not immunostained. It is notable that thalamocortical afferent fibers were also immunostained specifically on E14. After birth, the localization of the antigen became less noticeable and by 3 weeks after birth, the antigen had substantially disappeared. In the developing cerebellum, prominent labeling was also observed in the molecular layer and outskirts of the cerebellar nuclei on early postnatal days. To characterize the glycoprotein bearing the Tn antigen biochemically, immunoblot analysis was performed. The glycoprotein, most of which was extracted with a salt solution, migrated as a broad smeared band corresponding to a molecular weight of about 250 kDa on SDS-PAGE. Among the various tissues examined, this glycoprotein was only detected in the brain and its amount increased until an early postnatal stage with a peak on postnatal day 3 (P3), and then decreased gradually with age. This spatially and developmentally regulated expression of the Tn antigen suggests that this antigen plays a significant role in brain development.


Assuntos
Antígenos Glicosídicos Associados a Tumores/metabolismo , Sistema Nervoso Central/metabolismo , Glicoproteínas/metabolismo , Neurônios/metabolismo , Vias Aferentes/embriologia , Vias Aferentes/crescimento & desenvolvimento , Vias Aferentes/metabolismo , Envelhecimento/imunologia , Animais , Animais Recém-Nascidos , Especificidade de Anticorpos/fisiologia , Antígenos Glicosídicos Associados a Tumores/imunologia , Axônios/metabolismo , Sistema Nervoso Central/embriologia , Sistema Nervoso Central/crescimento & desenvolvimento , Cerebelo/embriologia , Cerebelo/crescimento & desenvolvimento , Cerebelo/metabolismo , Córtex Cerebral/embriologia , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Feto , Glicoproteínas/imunologia , Immunoblotting , Imuno-Histoquímica , Lectinas/imunologia , Camundongos , Camundongos Endogâmicos ICR , Neurônios/citologia , Medula Espinal/embriologia , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/metabolismo , Tálamo/embriologia , Tálamo/crescimento & desenvolvimento , Tálamo/metabolismo
12.
Brain Res ; 906(1-2): 1-12, 2001 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-11430856

RESUMO

To elucidate which glutamate receptors, NMDA or non-NMDA, have the main role in synaptic transmission via unmyelinated afferents in the trigeminal subnucleus caudalis (the medullary dorsal horn), and to examine the early functional effects of neonatal capsaicin treatment to the subnucleus caudalis, optical recording, field potential recording, and quantitative study using electron micrographs were employed. A medulla oblongata isolated from a rat 5--7 days old was sectioned horizontally 400-microm thick or parasagittally and stained with a voltage-sensitive dye, RH482 or RH795. Single-pulse stimulation with high intensity to the trigeminal afferents evoked optical responses mainly in the subnucleus caudalis. The optical signals were composed of two phases, a fast component followed by a long-lasting component. The spatiotemporal properties of the optical signals were well correlated to those of the field potentials recorded simultaneously. The fast component was eliminated by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 10 microM), while the long-lasting component was not. The latter increased in amplitude under a condition of low Mg(2+) but was significantly reduced by DL-2-amino-5-phosphonovaleric acid (AP5; 30 microM). Neonatal capsaicin treatment also reduced the long-lasting component markedly. In addition, the decreases in the ratio of unmyelinated axons to myelinated axons and in the ratio of unmyelinated axons to Schwann cell subunits of trigeminal nerve roots both showed significant differences (P<0.05, Student's t-test) between the control group and the neonatal capsaicin treatment group. This line of evidence indirectly suggests that synaptic transmission via unmyelinated afferents in the subnucleus caudalis is mediated substantially by NMDA glutamate receptors and documented that neonatal capsaicin treatment induced a functional alteration of the neural transmission in the subnucleus caudalis as well as a morphological alteration of primary afferents within several days after the treatment.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Vias Aferentes/efeitos dos fármacos , Capsaicina/farmacologia , Bulbo/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Núcleo Inferior Caudal do Nervo Trigêmeo/efeitos dos fármacos , 2-Amino-5-fosfonovalerato/farmacologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Potenciais de Ação/fisiologia , Vias Aferentes/crescimento & desenvolvimento , Vias Aferentes/ultraestrutura , Animais , Animais Recém-Nascidos/anatomia & histologia , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/metabolismo , Contagem de Células , Estimulação Elétrica , Processamento Eletrônico de Dados , Antagonistas de Aminoácidos Excitatórios/farmacologia , Corantes Fluorescentes/farmacocinética , Deficiência de Magnésio/fisiopatologia , Bulbo/crescimento & desenvolvimento , Bulbo/ultraestrutura , Microscopia Eletrônica , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/metabolismo , Fibras Nervosas/ultraestrutura , Fibras Nervosas Mielinizadas/ultraestrutura , Neurônios Aferentes/metabolismo , Neurônios Aferentes/ultraestrutura , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Nociceptores/ultraestrutura , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Estirenos/farmacocinética , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Núcleo Inferior Caudal do Nervo Trigêmeo/crescimento & desenvolvimento , Núcleo Inferior Caudal do Nervo Trigêmeo/ultraestrutura
13.
J Comp Neurol ; 416(2): 131-42, 2000 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-10581461

RESUMO

Birthdates of the neurons that comprise the layers of the mature visual cortex in the wallaby (Macropus eugenii) have been determined with the aid of tritiated thymidine autoradiography. The laminar positions of cells, identified by their birthdates, have then been followed at early stages during development and compared with previously published data on the distribution of thalamocortical afferents and corticothalamic projecting cells (Sheng et al. [1991] J. Comp. Neurol. 307:17-38). Neurons are born in a deep to superficial sequence typical of other mammals. The loosely packed zone of cells, which develops at the base of the thin compact zone of cells at the superficial margin of the cortical plate early in development, was identified as being part of the cortical plate. Afferents did not wait below this zone but grew into the developing cortical layers immediately after the cells that form these layers began accumulating in the loosely packed zone, starting with layer 6 on postnatal day 22 (P22). The genesis of layer 4 did not begin until P32, and these cells reached the superficial cortical plate at P54 and entered the loosely packed zone by P65. Cells of layers 5 and 6 formed the initial projection to the thalamus. Despite the protracted development of the wallaby and the large discrepancy between the time of thalamic ingrowth and genesis of layer 4, there was no extended waiting period for afferents in the subplate.


Assuntos
Vias Aferentes/crescimento & desenvolvimento , Macropodidae/anatomia & histologia , Neurônios/citologia , Tálamo/crescimento & desenvolvimento , Córtex Visual/crescimento & desenvolvimento , Animais , Córtex Visual/citologia
14.
J Neurosci ; 19(18): 7940-50, 1999 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10479695

RESUMO

The development of the different, highly specialized regions of the mammalian cerebral cortex depends in part on neural activity, either intrinsic spontaneous activity or externally driven sensory activity. To determine whether patterned sensory activity instructs the development of intrinsic cortical circuitry, we have experimentally altered the modality of sensory inputs to cerebral cortex. Neonatal diversion of retinal axons to the auditory thalamus (cross-modal rewiring) results in a primary auditory cortex (AI) that resembles visual cortex in its response properties and topography (Roe et al., 1990, 1992). To test the hypothesis that the visual response properties are created by a visually driven reorganization of auditory cortical circuitry, we investigated the effect of early visual experience on the development of intrinsic, horizontal connections within AI. Horizontal connections are likely to play an important role in the construction of visual response properties in AI as they do in visual cortex. Here we show that early visual inputs to auditory thalamus can reorganize horizontal connections in AI, causing both an increase in their extent and a change in pattern, so that projections are not restricted to the isofrequency axis, but extend in a more isotropic pattern around the injection site. Thus, changing afferent modality, without altering the source of the thalamocortical axons, can profoundly alter cortical circuitry. Similar changes may underlie cortical compensatory processes in deaf or blind humans and may also have played a role in the parcellation of neocortex during mammalian evolution.


Assuntos
Envelhecimento , Córtex Auditivo/fisiologia , Córtex Cerebral/fisiologia , Tálamo/fisiologia , Vias Visuais/fisiologia , Vias Aferentes/crescimento & desenvolvimento , Vias Aferentes/fisiologia , Animais , Animais Recém-Nascidos , Córtex Auditivo/anatomia & histologia , Córtex Auditivo/crescimento & desenvolvimento , Axônios/fisiologia , Córtex Cerebral/crescimento & desenvolvimento , Furões , Retina/fisiologia , Tálamo/crescimento & desenvolvimento , Vias Visuais/crescimento & desenvolvimento
15.
J Comp Neurol ; 364(3): 494-514, 1996 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-8820879

RESUMO

This paper is the second in a series which makes use of the protracted postnatal maturation of the wallaby to study the development of the trigeminal sensory system. Previous work has established similarities in the organisation of the trigeminal sensory system in the wallaby and in rodents. This study describes the structure and development of the ventroposteromedial nucleus in the wallaby in relationship to the arrival of afferents from the trigeminal nuclei, the formation of neuronal aggregations and naturally occurring cell death. Enzyme histochemistry, Nissl and myelin stains were used. Pathway development was followed using carbocyanine dyes. In the adult wallaby the nucleus demonstrates evidence of a parcellated organisation. Cells are arranged in dorsoventrally aligned bands resembling fingers. In the horizontal plane, these appear as circular clusters which are encircled by fine myelinated bundles. The clusters of cells are believed to correspond to the mystacial vibrissae. The first afferents from the principal trigeminal nucleus arrive between 10 and 15 days postnatal. This is more than two weeks prior to the time at which the borders of the nucleus can be discerned cytoarchitecturally. The first hints of segmentation are visible around day 50, and discrete aggregations form over the ensuing 3-4 weeks. Coincident with the aggregation of the neurons is an increase in their level of reactivity for acetylcholinesterase. A high level of acetylcholinesterase reactivity is maintained for at least 4 months, but has disappeared in adult animals. The peak of cell death occurs subsequent to the appearance of aggregations in the thalamus, but coincident with the appearance of vibrissae related patches in the cortex at day 85 (Waite et al. [1991] Dev. Brain Res. 58:35-41). The timing of the appearance of the neuronal aggregations supports the hypothesis that pattern formation occurs sequentially at successive levels of the pathway, and suggests the importance of target maturation in pattern formation.


Assuntos
Tronco Encefálico/crescimento & desenvolvimento , Macropodidae/fisiologia , Tálamo/crescimento & desenvolvimento , Nervo Trigêmeo/crescimento & desenvolvimento , Vias Aferentes/citologia , Vias Aferentes/crescimento & desenvolvimento , Animais , Tronco Encefálico/citologia , Agregação Celular , Contagem de Células , Morte Celular , Histocitoquímica , Tálamo/citologia , Nervo Trigêmeo/citologia , Vibrissas/fisiologia
16.
Prog Brain Res ; 108: 41-54, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8979793

RESUMO

One of the basic tasks of neurobiology is to understand how the precision and specificity of neuronal connections is achieved during development. In this paper we reviewed some recent in vitro studies on the developing mammalian cerebral cortex that have been made towards this end. The results of these experiments provided evidence that membrane-associated molecules are instrumental for the formation of specific afferent and efferent cortical projections. Substrate-bound molecules guide growing axons towards their target, regulate the timing of thalamocortical innervation and mediate target cell recognition. Moreover, a newly described glycoprotein, defined by a monoclonal antibody, revealed a molecular heterogeneity in the developing white matter. Since this molecule has opposite effects on thalamic and cortical axons, it might play a role in the segregation of axons running to and from the cortex. Substrate-bound cues are important during the formation of local cortical circuits. In vitro assays demonstrated that molecular components confined to individual cortical layers control the laminar specificity of cortical axon branching. This suggests that similar developmental strategies contribute to the laminar specification of extrinsic and intrinsic cortical circuits. Thus substrate-bound molecules might provide the framework for subsequent activity-dependent mechanisms that control the elaboration of precise connections between the cortical columns. A major challenge ahead is to identify the factors that mediate these processes and to determine their mode of action. Recently, two families of proteins, the netrins and the semaphorins/collapsins, have been identified as growth cone signals in the developing spinal cord (reviewed in Goodman, 1994; Colamarino and Tessier-Lavigne, 1995a; Dodd and Schuchardt, 1995; Kennedy and Tessier-Lavigne, 1995). Semaphorins/collapsins appear to regulate axonal guidance by repelling growth cones and by inhibiting axonal branching and synapse formation. Originally, netrins have been purified as diffusible chemoattractants for commissural axons of the dorsal spinal cord, but it is now well established that they can also function as chemorepellent factors for other classes of neurons. Since netrins are related to extracellular matrix components and since they can bind to the cell surface, they might also act as local guidance cues. A possible role of netrins and semaphorins/collapsins in the development of cortical connections is likely to be resolved in the near future. The identification of the factors that regulate specific branching patterns of cortical neurons might provide a better understanding of cortical development, but it might also be relevant to some aspects of plasticity and repair in the adult cortex.


Assuntos
Córtex Cerebral/crescimento & desenvolvimento , Vias Aferentes/crescimento & desenvolvimento , Vias Aferentes/ultraestrutura , Córtex Cerebral/ultraestrutura , Vias Eferentes/crescimento & desenvolvimento , Vias Eferentes/ultraestrutura , Neurônios/ultraestrutura , Tálamo/crescimento & desenvolvimento , Tálamo/ultraestrutura
17.
Neurosci Lett ; 180(2): 188-92, 1994 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-7535406

RESUMO

The distribution of the neuronal isoform of the enzyme nitric oxide synthase (type 1) has been investigated in the lumbar spinal cords of neonatal rats (2-20 days old). Large multipolar neurones were present from day 2 around the central canal, in a band across the neck of the dorsal horn and at the thoracic level in the intermediolateral cell column, whereas staining was absent from laminae II. By 20 days the laminae II staining was similar to that found in the adult. NOS expression in lamina II paralleled the development of c-fos expression in this lamina in response to peripheral application of mustard oil.


Assuntos
Aminoácido Oxirredutases/biossíntese , Toxidermias/fisiopatologia , Regulação da Expressão Gênica no Desenvolvimento , Irritantes/toxicidade , Proteínas do Tecido Nervoso/biossíntese , Neurônios/enzimologia , Extratos Vegetais/toxicidade , Proteínas Proto-Oncogênicas c-fos/biossíntese , Medula Espinal/enzimologia , Administração Tópica , Vias Aferentes/crescimento & desenvolvimento , Aminoácido Oxirredutases/genética , Animais , Animais Recém-Nascidos , Toxidermias/etiologia , Toxidermias/genética , Indução Enzimática , , Irritantes/administração & dosagem , Mostardeira , Proteínas do Tecido Nervoso/genética , Óxido Nítrico Sintase , Dor/fisiopatologia , Extratos Vegetais/administração & dosagem , Óleos de Plantas , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Medula Espinal/efeitos dos fármacos , Medula Espinal/crescimento & desenvolvimento
18.
J Neurocytol ; 21(2): 148-56, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1560251

RESUMO

A dense laminar network of varicose neuropeptide Y immunopositive fibres, but not cells, was found to cover the retinorecipient layers of the entire optic tectum of 10- to 21-day-old domestic chicks. Unilateral enucleation resulted in no apparent loss of neuropeptide Y immunopositive fibres in the contralateral tectum, suggesting that they are not of retinal origin. To identify possible sources of neuropeptide Y immunopositive tectal input, the distribution of neuropeptide Y immunopositive perikarya was investigated in the meso-diencephalic region of the chick. A virtually continuous network of neuropeptide Y immunopositive cells and fibres was observed stretching from rostro-lateral thalamus to the pretectum in close apposition to the perirotundal belt. These neuropeptide Y immunopositive structures did not seem to respect the borders of known anatomical regions but partially co-localized with the nucl. dorsolateralis anterior pars magnocellularis and pars medialis, nucl. pretectalis diffusus, nucl. lentiformis mesencephali pars parvocellularis and pars magnocellularis, nucl. principalis precommissuralis, nucl. lateralis precommissuralis, nucl. superficialis magnocellularis (SM), nucl. posteroventralis thalami Kühlenbeck and the nucl. subrotundus. In the nucleus of the basal optic root, neuropeptide Y immunopositive perikarya were observed only within or adjacent to its dorsal and lateral subdivisions although all subdivisions were enmeshed with neuropeptide Y immunopositive fibres. The neuropeptide Y immunopositive tectal input is likely to derive from tectothalamic--presumably perirotundal--neuronal groups. The extent of this tectal afferent projection, not reported earlier in the domestic chick, suggests a powerful neuropeptide-Yergic control of retinotectal relay function.


Assuntos
Neuropeptídeo Y/análise , Colículos Superiores/anatomia & histologia , Vias Aferentes/crescimento & desenvolvimento , Animais , Galinhas/crescimento & desenvolvimento , Enucleação Ocular , Feminino , Masculino , Células Ganglionares da Retina , Colículos Superiores/química , Tálamo/anatomia & histologia , Tálamo/química
19.
J Hirnforsch ; 33(4-5): 515-44, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1479192

RESUMO

The retinocerebral projections of Emys orbicularis were investigated by means of [3H]-proline or HRP, administered by intraocular injection. Two newly-hatched, two juvenile and seven adult specimens were examined. The results reveal contralateral retinal projections to fifteen sites: two in the hypothalamus (the nuclei suprachiasmaticus and periventricularis), five in the thalamus (the nuclei ovalis, geniculatus lateralis ventralis, geniculatus laleralis dorsalis, dorsolateralis anterior and ventrolateralis), five in the pretectal region (the nuclei geniculatus pretectalis, opticus pretectalis ventrolateralis, lentiformis mesencephali, posterodorsalis and griseus tectalis), two in the optic tectum (the stratum opticum and the stratum fibrosum et griseum superficiale), and one in the tegmentum (the nucleus opticus tegmenti). Ipsilateral projections to nine of these sites at thalamic, pretectal, tectal and tegmental levels, while weak, could be clearly demonstrated. These results differ considerably from those obtained in a previous investigation using a Nauta-paraffin technique; it is suggested that the differences are due to limitations of the latter technique. A review of the existing literature on the Chelonian primary visual system reveals considerable terminological diversity, and a standard nomenclature for the primary visual centres of turtles is proposed.


Assuntos
Vias Aferentes/anatomia & histologia , Encéfalo/anatomia & histologia , Tartarugas/anatomia & histologia , Vias Visuais/anatomia & histologia , Vias Aferentes/crescimento & desenvolvimento , Envelhecimento/fisiologia , Animais , Encéfalo/crescimento & desenvolvimento , Corpos Geniculados/anatomia & histologia , Peroxidase do Rábano Silvestre , Hipotálamo/anatomia & histologia , Mesencéfalo/anatomia & histologia , Fibras Nervosas/fisiologia , Fibras Nervosas/ultraestrutura , Prolina , Retina/anatomia & histologia , Retina/crescimento & desenvolvimento , Colículos Superiores/anatomia & histologia , Tálamo/anatomia & histologia , Trítio , Vias Visuais/crescimento & desenvolvimento
20.
J Neurosci Res ; 31(1): 156-65, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1613820

RESUMO

The mutant hypogonadal (hpg) mouse lacks a functioning gene for the neurohormone gonadotropin releasing hormone (GnRH). Previous studies from our laboratory had indicated that the initiation and maintenance of reproductive function in these mice could be brought about by the implantation of normal fetal grafts into adult hosts. Testicular or ovarian growth and other indicators of normal neurosecretory output were always accompanied by survival of GnRH neurons and growth of GnRH axons into the host median eminence where such axons terminate on the hypophysial portal capillaries. To determine if other connections exist between graft and the host hypothalamus, small crystals of the carbocyanine dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) were applied to either graft or host after fixation of the brain. Tissue sections were analyzed for retrograde and and anterograde movement of the dye. When crystals were placed on the graft, labeled axons were found in the host median eminence or in the host hypothalamus taking an arching trajectory toward the median eminence. Retrogradely labeled neurons in the host were few in number and largely confined to the host arcuate nucleus. With DiI crystals applied to the basal hypothalamus, labeled axons were distributed widely in the host but much sparser in the graft. Axons appeared to enter primarily at sites where the graft and host interface lacked an ependymal lining. Small numbers of retrogradely labeled neurons were also seen in the graft. Most were cells of very simple morphology and were distributed randomly in the graft. When double label experiments were carried out most DiI positive cells in the graft contained GnRH. These results indicate the connectivity between host hypothalamus and the third ventricular preoptic area grafts exists but is limited in nature.


Assuntos
Transplante de Tecido Encefálico , Carbocianinas , Ventrículos Cerebrais , Transplante de Tecido Fetal , Hipogonadismo/cirurgia , Hipotálamo/patologia , Camundongos Mutantes , Área Pré-Óptica , Septo Pelúcido/transplante , Vias Aferentes/crescimento & desenvolvimento , Animais , Axônios/ultraestrutura , Vias Eferentes/crescimento & desenvolvimento , Feminino , Hormônio Liberador de Gonadotropina/deficiência , Hormônio Liberador de Gonadotropina/genética , Hipogonadismo/genética , Hipogonadismo/patologia , Masculino , Camundongos , Neurônios/patologia , Tamanho do Órgão , Ovário/patologia , Área Pré-Óptica/embriologia , Septo Pelúcido/embriologia , Testículo/patologia , Transplante Heterotópico
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