RESUMEN
OBJECTIVE: The development of retinotectal pathways form precise topographical maps is usually completed by the third postnatal week. Cytokines participate in the development and plasticity of the nervous system. We have previously shown that in vivo treatment with interleukin 2 disrupts the retinocollicular topographical order in early stages of development. Therefore, we decided to study the effect of a single intravitreous injection of IL-6 upon retinotectal circuitry in neonates and juvenile rats. MATERIALS AND METHODS: Lister Hooded rats received an intravitreous injection of IL-6 (50 ng/ml) or vehicle (PBS) at either postnatal day (PND)10 or PND30 and the ipsilateral retinotectal pathway was evaluated 4 or 8 days later, respectively. RESULTS: Our data showed that, at different stages of development, a single IL-6 intravitreous treatment did not produce an inflammatory response and increased retinal axon innervation throughout the visual layers of the superior colliculus. CONCLUSIONS: Taken together, our data provide the first evidence that a single intravitreous injection with IL-6 leads to sprouting in the subcortical visual connections and suggest that small changes in IL-6 levels might be sufficient to impair the correct neuronal circuitry fine-tuning during brain development.
Asunto(s)
Interleucina-6/administración & dosificación , Retina/crecimiento & desarrollo , Colículos Superiores/crecimiento & desarrollo , Vías Visuales/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Inyecciones Intravítreas , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Ratas , Retina/citología , Retina/efectos de los fármacos , Colículos Superiores/citología , Colículos Superiores/efectos de los fármacos , Vías Visuales/citología , Vías Visuales/efectos de los fármacosRESUMEN
During early postnatal development retinocollicular projections undergo activity-dependent synaptic refinement that results in the formation of precise topographical maps in the visual layers of the superior colliculus (SC). Amyloid Precursor Protein (APP) is a widely expressed transmembrane glycoprotein involved in the regulation of several aspects of neural development, such as neurite outgrowth, synapse formation and plasticity. Stimulation of cholinergic system has been found to alter the expression and processing of APP in different cell lines. Herein, we investigated the effect of nicotine on the development of retinocollicular pathway and on APP metabolism in the SC of pigmented rats. Animals were submitted to intracranial Elvax implants loaded with nicotine or phosphate-buffered saline (vehicle) at postnatal day (PND) 7. The ipsilateral retinocollicular pathway of control and experimental groups was anterogradely labeled either 1 or 3 weeks after surgery (PND 14 or PND 28). Local nicotine exposure produces a transitory sprouting of uncrossed retinal axons outside their main terminal zones. Nicotine also increases APP content and its soluble neurotrophic fragment sAPPα. Furthermore, nicotine treatment upregulates nicotinic acetylcholine receptor α7 and ß2 subunits. Taken together, these data indicate that nicotine disrupts the ordering and topographic mapping of axons in the retinocollicular pathway and facilitates APP processing through the nonamyloidogenic pathway, suggesting that sAPPα may act as a trophic agent that mediates nicotine-induced morphological plasticity.
Asunto(s)
Precursor de Proteína beta-Amiloide/metabolismo , Plasticidad Neuronal/efectos de los fármacos , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Retina/efectos de los fármacos , Colículos Superiores/efectos de los fármacos , Animales , Western Blotting , Implantes de Medicamentos , Técnicas de Trazados de Vías Neuroanatómicas , Plasticidad Neuronal/fisiología , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Fotomicrografía , Polivinilos , Ratas , Receptores Nicotínicos/metabolismo , Retina/citología , Retina/crecimiento & desarrollo , Retina/fisiología , Colículos Superiores/citología , Colículos Superiores/crecimiento & desarrollo , Colículos Superiores/fisiología , Vías Visuales/citología , Vías Visuales/efectos de los fármacos , Vías Visuales/crecimiento & desarrollo , Vías Visuales/fisiología , Receptor Nicotínico de Acetilcolina alfa 7/metabolismoRESUMEN
INTRODUCTION: Glycine and the gamma-aminobutyric acid are the principal inhibitory neurotransmitters in the vertebrate retina. The inhibitory action of glycine is mediated by the post-synaptic glycine receptor, a chloride-selective channel, constituted by three beta and two alpha subunits (alpha(1)-alpha(4)), which is antagonized by the alkaloid strychnine. In the retina, it is known that all alpha isoforms are expressed at the level of the inner synaptic layer with a very low colocalization. The glycine receptor formed by either alpha1 or alpha(3) shows rapid kinetics, whereas alpha(2) or alpha(4) receptors respond tonically. The use of transgenic mice has allowed the study of the different glycine receptor alpha subunits in the glycinegic neurotransmission of the mammalian retina. AIM: To describe the participation of the glycine receptor in the inhibitory neurotransmission particularly in the retina. DEVELOPMENT: In this review we describe the experiments that have allowed the localization and the involvement of the alpha subunit isoforms in specific transmission circuits of the vertebrate retina. CONCLUSIONS: The localization of the glycine receptor conformed by different isoforms of the alpha subunit in specific neuronal types, indicate the presence of glycinergic circuits that encode information differently in the retina.
Asunto(s)
Proteínas del Ojo/fisiología , Glicina/fisiología , Potenciales Postsinápticos Inhibidores , Receptores de Glicina/fisiología , Retina/fisiología , Células Amacrinas/efectos de los fármacos , Células Amacrinas/fisiología , Animales , Cloruros/metabolismo , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Potenciales Postsinápticos Inhibidores/fisiología , Ratones , Ratones Noqueados , Ratones Transgénicos , Isoformas de Proteínas/fisiología , Subunidades de Proteína , Receptores de Glicina/efectos de los fármacos , Células Bipolares de la Retina/efectos de los fármacos , Células Bipolares de la Retina/fisiología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/fisiología , Estricnina/farmacología , Transmisión Sináptica , Vertebrados/metabolismo , Vías Visuales/efectos de los fármacos , Vías Visuales/fisiologíaRESUMEN
To investigate the contribution of feedback circuits from area V4 to the receptive-field properties of V2 neurons, we used tungsten microelectrodes to record extracellular single units in these visual areas, before and after pressure injections of a solution of 0.25 mol/L of GABA in two anesthetized and paralyzed Cebus apella monkeys. The visual stimulus consisted of a single bar moving in one of eight directions. Using a device made of four stainless steel pipettes and one central tungsten electrode, we inactivated, with different amounts of GABA, topographically corresponding areas of V4, while studying V2 neurons. We studied a total of 36 V2 neurons during six sessions of GABA injections into area V4. GABA inactivation of visual area V4 produced a general decrease in the excitability of the neurons, which included a decrease in spontaneous and driven activities, followed by changes in direction selectivity. The changes in selectivity were toward an increase in directional selectivity and decrease in orientation selectivity. Thus, feedback connections arising from V4, an area of the ventral steams of visual information processing, are capable of not only modulating the spontaneous and driven activity of V2 neurons, but also of modifying V2 receptive field properties, such as its direction and/or orientation selectivity.
Asunto(s)
Inhibición Neural/fisiología , Neuronas/fisiología , Corteza Visual/fisiología , Campos Visuales/fisiología , Vías Visuales/fisiología , Ácido gamma-Aminobutírico/farmacología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Cebus , Masculino , Inhibición Neural/efectos de los fármacos , Neuronas/efectos de los fármacos , Estimulación Luminosa/métodos , Corteza Visual/efectos de los fármacos , Campos Visuales/efectos de los fármacos , Vías Visuales/efectos de los fármacos , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
Interleukin-2 (IL-2) plays regulatory functions both in immune and nervous system. However, in the visual system, little is known about the cellular types which respond to IL-2 and its effects. Herein, we investigated the influence of IL-2 in the development of central visual pathways. Lister Hooded rats were submitted to multiple (at postnatal days [PND]7/10/13) or single (at PND10) intravitreous injections of phosphate-buffered saline (PBS) (vehicle), zymosan, or IL-2. IL-2 receptor α subunit was detected in the whole postnatal retina. Chronic treatment with either PBS or IL-2 increases retinal glial fibrillary acidic protein (GFAP) expression, induces intravitreous inflammation revealed by the presence of macrophages, and results in a slight rearrangement of retinotectal axons. Acute zymosan treatment disrupts retinotectal axons distribution, confirming the influence of inflammation on retinotectal pathway reordering. Furthermore, acute IL-2 treatment increases GFAP expression in the retina without inflammation and produces a robust sprouting of the intact uncrossed retinotectal pathway. No difference was observed in glial cells activity in superior colliculus. Taken together, these data suggest that inflammation and interleukin-2 modulate retinal ganglion cells development and the distribution of their axons within central targets.
Asunto(s)
Analgésicos no Narcóticos/efectos adversos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Interleucina-2/efectos adversos , Neuroglía/efectos de los fármacos , Retina/crecimiento & desarrollo , Vías Visuales/crecimiento & desarrollo , Análisis de Varianza , Animales , Animales Recién Nacidos , Proteína Ácida Fibrilar de la Glía , Peroxidasa de Rábano Silvestre/metabolismo , Inflamación/inducido químicamente , Inflamación/patología , Inyecciones Intravítreas , Neuroglía/metabolismo , Ratas , Receptores de Interleucina-2/metabolismo , Retina/anatomía & histología , Retina/efectos de los fármacos , Retina/metabolismo , Vías Visuales/anatomía & histología , Vías Visuales/efectos de los fármacosRESUMEN
Adenosine is a neuromodulator implicated in nervous system development and plasticity and its effects are mediated by inhibitory (A(1), A(3)) and excitatory (A(2a), A(2b)) receptors. The role of adenosine in the synaptic activity depends mainly on a balanced activation of A(1) and A(2a) receptors which are activated by various ranges of adenosine concentrations. Herein, we investigated the expression of A(1) and A(2a) receptors and also the accumulation of cAMP in the superior colliculus at different stages of development. Furthermore, we examined the effects of an acute in vivo blockade of adenosine deaminase during the critical period when the elimination of misplaced axons/terminals takes place with a simultaneous fine tuning of terminal arbors into appropriate terminal zones. Lister Hooded rats ranging from postnatal days (PND) 0-70 were used for ontogeny studies. Our results indicate that A(1) expression in the visual layers of the superior colliculus is higher until PND 28, while A(2a) expression increases after PND 28 in a complementary developmental pattern. Accordingly, the incubation of collicular slices with 5'-N-ethylcarboxamido-adenosine, a non-specific adenosine receptor agonist, showed a significant reduction in cAMP accumulation at PND 14 and an increase in adults. For the anatomical studies, the uncrossed retinotectal projections were traced after the intraocular injection of horseradish peroxidase. One group received daily injections of an adenosine deaminase inhibitor (erythro-9(2-hydroxy-3-nonyl adenine), 10 mg/kg i.p.) between PND 10 and 13, while control groups were treated with vehicle injections (NaCl 0.9%, i.p.). We found that a short-term blockade of adenosine deaminase during the second postnatal week induced an expansion of retinotectal terminal fields in the rostrocaudal axis of the tectum. Taken together, the results suggest that a balance of purinergic A(1) and A(2a) receptors through cAMP signaling plays a pivotal role during the development of topographic order in the retinotectal pathway.
Asunto(s)
AMP Cíclico/metabolismo , Receptor de Adenosina A1/metabolismo , Receptor de Adenosina A2A/metabolismo , Retina/crecimiento & desarrollo , Colículos Superiores/crecimiento & desarrollo , Adenina/análogos & derivados , Adenina/farmacología , Agonistas del Receptor de Adenosina A1 , Agonistas del Receptor de Adenosina A2 , Inhibidores de la Adenosina Desaminasa , Adenosina-5'-(N-etilcarboxamida)/farmacología , Animales , Animales Recién Nacidos , Fármacos del Sistema Nervioso Central/farmacología , Inhibidores Enzimáticos/farmacología , Peroxidasa de Rábano Silvestre , Trazadores del Tracto Neuronal , Ratas , Ratas Endogámicas , Retina/anatomía & histología , Retina/efectos de los fármacos , Colículos Superiores/anatomía & histología , Colículos Superiores/efectos de los fármacos , Vías Visuales/anatomía & histología , Vías Visuales/efectos de los fármacos , Vías Visuales/crecimiento & desarrolloRESUMEN
The use-dependent specification of neural circuits occurs during post-natal development with a conspicuous influence of environmental factors, such as malnutrition that interferes with the major steps of brain maturation. Serotonin (5-HT), derived exclusively from the essential aminoacid tryptophan, is involved in mechanisms of development and use-dependent plasticity of the central nervous system. We studied the effects of the nutritional restriction of tryptophan in the plasticity of uncrossed retinotectal axons following a retinal lesion to the contralateral retina during the critical period in pigmented rats. Litters were fed through their mothers with a low tryptophan content diet, based on corn and gelatin, a complemented diet with standard tryptophan requirements for rodents or standard laboratory diet. The results suggest a marked reduction in the plasticity of intact axons into denervated territories in the tryptophan restricted group in comparison to control groups. Tryptophan complementation between PND10-21 completely restored retinotectal plasticity. However, the re-introduction of tryptophan after the end of the critical period (between PND28-P41) did not restore the sprouting ability of uncrossed axons suggesting a time-dependent effect to the reversion of plasticity deficits. Tryptophan-restricted animals showed a reduced activity of matrix metalloproteinase-9 and altered expressions of phosphorylated forms of ERK1/2 and AKT. Our results demonstrate the influence of this essential aminoacid as a modulator of neural plasticity during the critical period through the reduction of serotonin content which alters plasticity-related signaling pathways and matrix degradation.
Asunto(s)
Plasticidad Neuronal/fisiología , Retina/crecimiento & desarrollo , Triptófano/deficiencia , Vías Visuales/crecimiento & desarrollo , Factores de Edad , Animales , Animales Recién Nacidos , Axones/efectos de los fármacos , Axones/metabolismo , Axones/patología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/fisiología , Peroxidasa de Rábano Silvestre/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Red Nerviosa/crecimiento & desarrollo , Red Nerviosa/metabolismo , Plasticidad Neuronal/efectos de los fármacos , Proteína Oncogénica v-akt/metabolismo , Embarazo , Ratas , Retina/efectos de los fármacos , Retina/lesiones , Retina/metabolismo , Triptófano/administración & dosificación , Vías Visuales/efectos de los fármacos , Vías Visuales/metabolismoRESUMEN
Visual callosal fibers link cortical loci in opposite hemispheres that represent the same visual field but whose locations are not mirror-symmetric with respect to the brain midline. Presence of the eyes from postnatal day 4 (P4) to P6 is required for this map to be specified. We tested the hypothesis that specification of the callosal map requires the activation of A'-methyl-D-aspartate receptors (NMDARs). Our results show that blockade of NMDARs with MK-801 during this critical period did not induce obvious abnormalities in callosal connectivity patterns, suggesting that retinal influences do not operate through NMDAR-mediated processes to specify normal callosal topography. In contrast, we found that interfering with NMDAR function either through MK801-induced blockade of NMDARs starting at P6 or neonatal enucleation significantly increases the length of axon branches and total length of arbors, without major effects on the number of branch tips. Our results further suggest that NMDARs act by altering the initial elaboration of arbors rather than by inhibiting a later-occurring remodeling process. Since the callosal map is present by P6, just as axonal branches of simple architecture grow into gray matter, we suggest that regulation of arbor development by NMDAR-mediated processes is important for maintaining the precision of this map.
Asunto(s)
Animales , Ratas , Axones/fisiología , Cuerpo Calloso/crecimiento & desarrollo , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Vías Visuales/crecimiento & desarrollo , Animales Recién Nacidos , Axones/efectos de los fármacos , Mapeo Encefálico , Cuerpo Calloso/citología , Cuerpo Calloso/efectos de los fármacos , Enucleación del Ojo , Ratas Long-Evans , Receptores de N-Metil-D-Aspartato/metabolismo , Vías Visuales/citología , Vías Visuales/efectos de los fármacosRESUMEN
Visual callosal fibers link cortical loci in opposite hemispheres that represent the same visual field but whose locations are not mirror-symmetric with respect to the brain midline. Presence of the eyes from postnatal day 4 (P4) to P6 is required for this map to be specified. We tested the hypothesis that specification of the callosal map requires the activation of N-methyl-D-aspartate receptors (NMDARs). Our results show that blockade of NMDARs with MK-801 during this critical period did not induce obvious abnormalities in callosal connectivity patterns, suggesting that retinal influences do not operate through NMDAR-mediated processes to specify normal callosal topography. In contrast, we found that interfering with NMDAR function either through MK801-induced blockade of NMDARs starting at P6 or neonatal enucleation significantly increases the length of axon branches and total length of arbors, without major effects on the number of branch tips. Our results further suggest that NMDARs act by altering the initial elaboration of arbors rather than by inhibiting a later-occurring remodeling process. Since the callosal map is present by P6, just as axonal branches of simple architecture grow into gray matter, we suggest that regulation of arbor development by NMDAR-mediated processes is important for maintaining the precision of this map.
Asunto(s)
Axones/fisiología , Cuerpo Calloso/crecimiento & desarrollo , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Vías Visuales/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Axones/efectos de los fármacos , Mapeo Encefálico , Cuerpo Calloso/citología , Cuerpo Calloso/efectos de los fármacos , Enucleación del Ojo , Ratas , Ratas Long-Evans , Receptores de N-Metil-D-Aspartato/metabolismo , Vías Visuales/citología , Vías Visuales/efectos de los fármacosRESUMEN
There is a growing body of evidence on the role of nitric oxide (NO) in retinal physiology. Recently, interest has developed in the functional role of an alternative redox form of NO, namely nitroxyl (HNO/NO(-)), because it is formed by a number of diverse biochemical reactions. The aim of the present report was to comparatively analyze the effect of HNO and NO on the retinal nitridergic pathway in the golden hamster. For this purpose, sodium trioxodinitrate (Angeli's salt) and diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) were used as HNO and NO releasers, respectively. Angeli's salt and DEA/NO significantly decreased nitric oxide synthase activity. In addition, Angeli's salt (but not DEA/NO) significantly decreased l-arginine uptake. DEA/NO significantly increased cGMP accumulation at low micromolar concentrations, while Angeli's salt affected this parameter with a threshold concentration of 200muM. Although Angeli's salt and DEA/NO significantly diminished reduced glutathione and protein thiol levels in a similar way, DEA/NO was significantly more effective than AS in increasing S-nitrosothiol levels. None of these compounds increased retinal lipid peroxidation. These results suggest that HNO could regulate the hamster retinal nitridergic pathway by acting through a mechanism that only partly overlaps with that involved in NO response.
Asunto(s)
Neuronas Nitrérgicas/metabolismo , Óxido Nítrico/metabolismo , Óxidos de Nitrógeno/metabolismo , Retina/metabolismo , Vías Visuales/metabolismo , Animales , Antioxidantes/farmacología , Arginina/metabolismo , Cricetinae , GMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Mesocricetus , Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/efectos de los fármacos , Óxido Nítrico Sintasa/metabolismo , Nitritos/farmacología , Óxidos de Nitrógeno/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Compuestos de Amonio Cuaternario/farmacología , Retina/efectos de los fármacos , S-Nitrosotioles/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Vías Visuales/efectos de los fármacosRESUMEN
The uncrossed retinotectal projection of rats undergoes extensive axonal elimination and subsequent growth of axonal arbors in topographically appropriate territories within the first two/three postnatal weeks. Nitric oxide has been implicated in development and stabilization of synapses in the retinotectal pathway since blockade of nitric oxide synthesis disrupts the normal pattern of retinal innervation in subcortical nuclei. The present work investigated the role of arachidonic acid pathway in the development and maintenance of ipsilateral retinotectal axons. We also investigated the role of this retrograde messenger in the modulation of plasticity that follows retinal lesions in the opposite eye. Pigmented rats received systemic treatment with quinacrine, a phospholipase A2 inhibitor, indomethacin, a cyclooxygenase inhibitor, nordihydroguaiaretic acid, a 5-lipoxygenase inhibitor or vehicle during 4-8 days at various postnatal ages. Rats given a unilateral temporal retinal lesion were treated with either quinacrine or vehicle during the same period. For anterograde tracing of ipsilateral retinal projections, animals received intraocular injections of horseradish peroxidase. Before the third postnatal week no difference was observed in the laminar or topographic organization of the ipsilateral retinotectal projection between vehicle and treated rats in either normal or lesion conditions. After the third postnatal week, however, systemic blockade of phospholipase A2 or 5-lipoxygenase, but not cyclooxygenase induced sprouting of uncrossed axons throughout the collicular visual layers in unoperated rats. In retinal lesion groups, phospholipase A2 blockade increased the sprouting of uncrossed intact axons to the collicular surface in the same period. The results suggest that arachidonic acid or lipoxygenase metabolites play a role in the maintenance of the retinotectal synapses after the critical period and that the blockade of the arachidonic acid pathway induces reactive sprouting of retinal axons late in development.
Asunto(s)
Ácido Araquidónico/metabolismo , Transducción de Señal/fisiología , Vías Visuales/crecimiento & desarrollo , Vías Visuales/metabolismo , Animales , Animales Recién Nacidos , Inhibidores Enzimáticos/farmacología , Inmunohistoquímica , Indometacina/farmacología , Inhibidores de la Lipooxigenasa , Masoprocol/farmacología , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Fosfolipasas A/antagonistas & inhibidores , Fosfolipasas A2 , Prostaglandina-Endoperóxido Sintasas/farmacología , Quinacrina/farmacología , Ratas , Retina/lesiones , Transducción de Señal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Vías Visuales/efectos de los fármacosAsunto(s)
Anemia Ferropénica/complicaciones , Cognición , Hierro de la Dieta/administración & dosificación , Anemia Ferropénica/epidemiología , Animales , Vías Auditivas/efectos de los fármacos , Vías Auditivas/fisiología , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiología , Disponibilidad Biológica , Ritmo Circadiano , Países Desarrollados , Países en Desarrollo , Humanos , Absorción Intestinal , Hierro de la Dieta/farmacocinética , Destreza Motora/efectos de los fármacos , Destreza Motora/fisiología , Prevalencia , Vías Visuales/efectos de los fármacos , Vías Visuales/fisiologíaRESUMEN
In the rat visual system, the uncrossed retinotectal projection undergoes a topographical refinement within the first two postnatal weeks. We have studied the role of nitric oxide (NO), a retrograde messenger which couples pre- and postsynaptic activation, in the development of the uncrossed retinotectal projection and in the plasticity of this pathway as a result of a restricted retinal lesion in the opposite eye. During development, maximal nitric oxide synthase (NOS) activity was observed in homogenates of tectal tissue at postnatal day 5 (PND 5), followed by a two-step decrease at the end of the topographical fine tuning period (PND 21) and the adult stage (PND 42). We also tested the effects of an acute in vivo blockade of NOS during the development of both animals that had not been operated on, and lesioned animals. Animals ranging from PND 4 to PND 42 were treated either with the NOS inhibitor, L-nitro-arginine (Narg 50 mg/kg ip.) or vehicle (NaCl 0.9%) during 4 days (from PND 4-7 or PND 9-12) or 8 days (from PND 20-27 or PND 34-41). Reduction of NOS activity induced sprouting of the ipsilateral pathway up to the second postnatal week in the animals that had not been operated on. Rats that had been operated on, however, showed an amplification of the lesion-induced plasticity up to the fourth postnatal week under NOS blockade. The data suggest that NO plays a role in the stabilization of retinotectal synapses during the critical period of topographic refinement, and indicate that an acute blockade of retrograde signals enables plastic rearrangements in the visual system within this time window.
Asunto(s)
Plasticidad Neuronal/fisiología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Retina/fisiología , Colículos Superiores/fisiología , Animales , Arginina/metabolismo , Axones/efectos de los fármacos , Citrulina/biosíntesis , Inhibidores Enzimáticos/farmacología , NADPH Deshidrogenasa/antagonistas & inhibidores , NADPH Deshidrogenasa/metabolismo , Plasticidad Neuronal/efectos de los fármacos , Óxido Nítrico Sintasa/metabolismo , Nitroarginina/farmacología , Ratas , Ratas Endogámicas , Retina/crecimiento & desarrollo , Retina/cirugía , Colículos Superiores/efectos de los fármacos , Colículos Superiores/enzimología , Colículos Superiores/crecimiento & desarrollo , Vías Visuales/efectos de los fármacos , Vías Visuales/crecimiento & desarrollo , Vías Visuales/metabolismoRESUMEN
We studied the effect of fluoxetine, a selective serotonin reuptake inhibitor, in the development and lesion-induced plasticity of retinotectal axons in pigmented rats. Neonatal rats received a daily injection of either fluoxetine or vehicle from postnatal day 1 (PND 1) to PND 10 or from PND 14 to PND 28 (fluoxetine, 7.5 and 10.0 mg/kg, respectively). In the latter group, some animals received a single lesion at the temporal periphery of the left retina at PND 21. Unoperated animals were use as the control. At the end of the treatment, the animals received an intraocular injection of horseradish peroxidase (HRP) in the right (intact) eye to trace the uncrossed retinotectal pathway. Chronic fluoxetine treatment, induced, in unoperated rats, an expansion of the retinal terminal fields along the rostro-caudal axis of the tectum both in the PND 10 and PND 28 groups. Following a retinal lesion in the left eye at PND 21, the vehicle-treated group showed a small reorganization of the intact uncrossed projection. In this group only a few terminals were labeled invading the denervated tectal surface one-week after the lesion. Fluoxetine-treated animals on the other hand, showed a great amplification of plasticity with a conspicuous sprouting of the uncrossed retinal axons into denervated areas. The data suggest that fluoxetine induces extensive axonal rearrangements in neonatal and juvenile central nervous system and amplifies neuroplasticity following retinal lesions late in development.
Asunto(s)
Fluoxetina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Vías Visuales/efectos de los fármacos , Vías Visuales/fisiología , Envejecimiento/fisiología , Animales , Axones/efectos de los fármacos , Axones/fisiología , Plasticidad Neuronal/fisiología , Ratas , Ratas Endogámicas , Retina/efectos de los fármacos , Retina/fisiología , Colículos Superiores/fisiología , Transmisión Sináptica/efectos de los fármacosRESUMEN
Behavioral and electrophysiological measures were used to elucidate the retinal modulation of oculomotor control in the turtle. Eye movements were recorded following intravitreal applications of 2-amino-4-phosphonobutyrate (APB) and the GABA antagonists picrotoxin and bicuculline. Visual responses of single basal optic nucleus (BON) neurons of the accessory optic system were studied in parallel experiments. The effectiveness of APB, a glutamate analog thought to act selectively on the retinal ON pathway, was assessed independently by recording electroretinograms or ganglion cell activity. Injections of APB into the turtle's eye reduced or blocked the injected eye's ability to drive horizontal optokinetic nystagmus, as also observed in rabbit and cat (Knapp et al., 1988; Yucel et al., 1989). Single-unit recordings from the BON during APB superfusion (50-200 microM APB) of the contralateral retina demonstrated that these cells, which are direction-sensitive and respond to the offset of light flashes, have their responses to moving stimuli blocked by APB. During the APB effect, GABA antagonists were applied to the same eye. Although moderate doses of APB were sufficient to block optokinetic or BON light responses, the addition of GABA blockers still elicited a spontaneous temporal-to-nasal nystagmus (Ariel, 1989) or visually responsive yet direction-insensitive responses from BON cells (Schuerger et al., 1990). These results are discussed in terms of the retinal output to pathways involved in oculomotor control of optokinetic nystagmus.
Asunto(s)
Aminobutiratos/farmacología , Bicuculina/farmacología , Nistagmo Fisiológico/efectos de los fármacos , Nervio Oculomotor/fisiología , Picrotoxina/farmacología , Retina/fisiología , Animales , Electronistagmografía , Electrofisiología , Nervio Oculomotor/efectos de los fármacos , Estimulación Luminosa , Retina/efectos de los fármacos , Tortugas , Vías Visuales/efectos de los fármacos , Vías Visuales/fisiologíaRESUMEN
A subpopulation of retinal ganglion cells projecting to the pigeon ventral lateral geniculate nucleus was shown to contain cholecystokinin-like immunoreactivity. These ganglion cells were mainly distributed in the peripheral retina, and their somata sizes were medium to large (14-23 microns). Taken together with previous findings, these results indicate that the retinal input to the ventral geniculate is chemically heterogeneous.