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1.
Adv Exp Med Biol ; 1131: 73-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646507

RESUMO

Imaging techniques may overcome the limitations of electrode techniques to measure locally not only membrane potential changes, but also ionic currents. Here, we review a recently developed approach to image native neuronal Ca2+ currents from brain slices. The technique is based on combined fluorescence recordings using low-affinity Ca2+ indicators possibly in combination with voltage sensitive dyes. We illustrate how the kinetics of a Ca2+ current can be estimated from the Ca2+ fluorescence change and locally correlated with the change of membrane potential, calibrated on an absolute scale, from the voltage fluorescence change. We show some representative measurements from the dendrites of CA1 hippocampal pyramidal neurons, from olfactory bulb mitral cells and from cerebellar Purkinje neurons. We discuss the striking difference in data analysis and interpretation between Ca2+ current measurements obtained using classical electrode techniques and the physiological currents obtained using this novel approach. Finally, we show how important is the kinetic information on the native Ca2+ current to explore the potential molecular targets of the Ca2+ flux from each individual Ca2+ channel.


Assuntos
Canais de Cálcio , Neuroimagem , Animais , Cálcio/metabolismo , Canais de Cálcio/fisiologia , Dendritos/fisiologia , Humanos , Potenciais da Membrana/fisiologia , Imagem Óptica , Células Piramidais/fisiologia
2.
Eur J Neurosci ; 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30387216

RESUMO

Optogenetics is based on the selective expression of exogenous opsins by neurons allowing experimental control of their electrical activity using visible light. The interpretation of the results of optogenetic experiments is based on the assumption that light stimulation selectively acts on those neurons expressing the exogenous opsins without perturbing the activity of naive ones. Here, we report that light stimulation, of wavelengths and power in the range of those normally used in optogenetic experiments, consistently reduces the firing activity of naive Mitral Cells (MCs) and Tufted Neurons in the olfactory bulb as well as in Medium Spiny Neurons (MSNs) in the striatum. No such effect was observed for cerebellar Purkinje and hippocampal CA1 neurons. The effects on MC firing appear to be mainly due to a light-induced increase in tissue temperature, between 0.1 and 0.4°C, associated with the generation of a hyperpolarizing current and a modification of action potential (AP) shape. Therefore, light in the visible range can affect neuronal physiology in a cell-specific manner. Beside the implications for optogenetic studies, our results pave the way to investigating the use of visible light for therapeutic purposes in pathologies associated with neuronal hyperexcitability.

3.
Elife ; 72018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29489453

RESUMO

Both passive exposure and active learning through reinforcement enhance fine sensory discrimination abilities. In the olfactory system, this enhancement is thought to occur partially through the integration of adult-born inhibitory interneurons resulting in a refinement of the representation of overlapping odorants. Here, we identify in mice a novel and unexpected dissociation between passive and active learning at the level of adult-born granule cells. Specifically, while both passive and active learning processes augment neurogenesis, adult-born cells differ in their morphology, functional coupling and thus their impact on olfactory bulb output. Morphological analysis, optogenetic stimulation of adult-born neurons and mitral cell recordings revealed that passive learning induces increased inhibitory action by adult-born neurons, probably resulting in more sparse and thus less overlapping odor representations. Conversely, after active learning inhibitory action is found to be diminished due to reduced connectivity. In this case, strengthened odor response might underlie enhanced discriminability.

4.
Nat Neurosci ; 19(7): 876-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27273767

RESUMO

Hedonic value is a dominant aspect of olfactory perception. Using optogenetic manipulation in freely behaving mice paired with immediate early gene mapping, we demonstrate that hedonic information is represented along the antero-posterior axis of the ventral olfactory bulb. Using this representation, we show that the degree of attractiveness of odors can be bidirectionally modulated by local manipulation of the olfactory bulb's neural networks in freely behaving mice.


Assuntos
Comportamento Animal/fisiologia , Rede Nervosa/fisiologia , Bulbo Olfatório/fisiologia , Percepção Olfatória/fisiologia , Olfato/fisiologia , Animais , Masculino , Camundongos Endogâmicos C57BL , Odorantes/análise
5.
Physiol Rep ; 3(5)2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26019289

RESUMO

Afterhyperpolarization (AHP) is a principal feedback mechanism in the control of the frequency and patterning of neuronal firing. In principal projection neurons of the olfactory bulb, the mitral cells (MCs), the AHP is produced by three separate components: classical potassium-mediated hyperpolarization, and the excitatory and inhibitory components, which are generated by the recurrent dendrodendritic synaptic transmission. Precise spike timing is involved in olfactory coding and learning, as well as in the appearance of population oscillatory activity. However, the contribution of the AHP and its components to these processes remains unknown. In this study, we demonstrate that the AHP is developed with the MC firing frequency and is dominated by the potassium component. We also show that recurrent synaptic transmission significantly modifies MC AHP and that the strength of the hyperpolarization produced by the AHP in the few milliseconds preceding the action potential (AP) emission determines MC firing frequency and AP timing. Moreover, we show that the AHP area is larger in younger animals, possibly owing to increased Ca(2+) influx during MC firing. Finally, we show that olfactory experience selectively reduces the early component of the MC AHP (under 25 msec), thus producing a modification of the AP timing limited to the higher firing frequency. On the basis of these results, we propose that the AHP, and its susceptibility to be selectively modulated by the recurrent synaptic transmission and olfactory experience, participate in odor coding and learning by modifying the frequency and pattern of MC firing.

6.
J Physiol ; 592(13): 2751-69, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24710056

RESUMO

Odour perception depends closely on nutritional status, in animals as in humans. Insulin, the principal anorectic hormone, appears to be one of the major candidates for ensuring the link between olfactory abilities and nutritional status, by modifying processing in the olfactory bulb (OB), one of its main central targets. The present study investigates whether and how insulin can act in OB, by evaluating its action on the main output neurons activities, mitral cells (MCs), in acute rat OB slices. Insulin was found to act at two OB network levels: (1) on MCs, by increasing their excitability, probably by inhibiting two voltage-gated potassium (K(+)) channels; (2) on interneurons by modifying the GABAergic and on glutamatergic synaptic activity impinging on MCs, mainly reducing them. Insulin also altered the olfactory nerve (ON)-evoked excitatory postsynaptic currents in 60% of MCs. Insulin decreased or increased the ON-evoked responses in equal proportion and the direction of its effect depended on the initial neuron ON-evoked firing rate. Indeed, insulin tended to decrease the high and to increase the low ON-evoked firing rates, thereby reducing inter-MC response firing variability. Therefore, the effects of insulin on the evoked firing rates were not carried out indiscriminately in the MC population. By constructing a mathematical model, the impact of insulin complex effects on OB was assessed at the population activity level. The model shows that the reduction of variability across cells could affect MC detection and discrimination abilities, mainly by decreasing and, less frequently, increasing them, depending on odour quality. Thus, as previously proposed, this differential action of insulin on MCs across odours would allow this hormone to put the olfactory function under feeding signal control, given the discerning valence of an odour as a function of nutritional status.


Assuntos
Insulina/farmacologia , Bulbo Olfatório/efeitos dos fármacos , Percepção Olfatória , Potenciais de Ação/efeitos dos fármacos , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/fisiologia , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Interneurônios/fisiologia , Masculino , Modelos Neurológicos , Bulbo Olfatório/citologia , Bulbo Olfatório/fisiologia , Nervo Olfatório/efeitos dos fármacos , Nervo Olfatório/fisiologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Ratos , Ratos Wistar
7.
J Neurosci ; 32(11): 3748-58, 2012 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-22423095

RESUMO

We have previously shown that an experience-driven improvement in olfactory discrimination (perceptual learning) requires the addition of newborn neurons in the olfactory bulb (OB). Despite this advance, the mechanisms which govern the selective survival of newborn OB neurons following learning remain largely unknown. We propose that activity of the noradrenergic system is a critical mediator providing a top-down signal to control the selective survival of newly born cells and support perceptual learning. In adult mice, we used pharmacological means to manipulate the noradrenergic system and neurogenesis and to assess their individual and additive effects on behavioral performance on a perceptual learning task. We then looked at the effects of these manipulations on regional survival of adult-born cells in the OB. Finally, using confocal imaging and electrophysiology, we investigated potential mechanisms by which noradrenaline could directly influence the survival of adult-born cells. Consistent with our hypotheses, direct manipulation of noradrenergic transmission significantly effect on adult-born cell survival and perceptual learning. Specifically, learning required both the presence of adult-born cell and noradrenaline. Finally, we provide a mechanistic link between these effects by showing that adult-born neurons receive noradrenergic projections and are responsive to noradrenaline. Based upon these data we argue that noradrenergic transmission is a key mechanism selecting adult-born neurons during learning and demonstrate that top-down neuromodulation acts on adult-born neuron survival to modulate learning performance.


Assuntos
Neurônios Adrenérgicos/fisiologia , Aprendizagem/fisiologia , Neurogênese/fisiologia , Bulbo Olfatório/citologia , Bulbo Olfatório/crescimento & desenvolvimento , Percepção Olfatória/fisiologia , Fatores Etários , Animais , Sobrevivência Celular/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Odorantes , Distribuição Aleatória
8.
Pharmacol Ther ; 132(2): 170-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21718720

RESUMO

In the 1980s, Bowery and colleagues discovered the presence of a novel, bicuculline-resistant and baclofen-sensitive type of GABA receptor on peripheral nerve terminals, the GABA(B) receptor. Since this pioneering work, GABA(B) receptors have been identified in the Central Nervous System (CNS), where they provide an important inhibitory control of postsynaptic excitability and presynaptic transmitter release. GABA(B) receptors have been implicated in a number of important processes in the adult brain such as the regulation of synaptic plasticity and modulation of rhythmic activity. As a result of these studies, several potential therapeutic applications of GABA(B) receptor ligands have been identified. Recent advances have further shown that GABA(B) receptors play more than a classical inhibitory role in adult neurotransmission, and can in fact function as an important developmental signal early in life. Here we summarize current knowledge on the contribution of GABA(B) receptors to the construction and function of developing neuronal networks.


Assuntos
Sistema Nervoso Central/metabolismo , Rede Nervosa/metabolismo , Receptores de GABA-B/metabolismo , Animais , Humanos , Transmissão Sináptica
9.
J Neurochem ; 118(4): 533-45, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21255015

RESUMO

Recent studies have shown that GABA(B) receptors play more than a classical inhibitory role and can function as an important synaptic maturation signal early in life. In a previous study, we reported that GABA(B) receptor activation triggers secretion of brain-derived neurotrophic factor (BDNF) and promotes the functional maturation of GABAergic synapses in the developing rat hippocampus. To identify the signalling pathway linking GABA(B) receptor activation to BDNF secretion in these cells, we have now used the phosphorylated form of the cAMP response element-binding protein as a biological sensor for endogenous BDNF release. In the present study, we show that GABA(B) receptor-induced secretion of BDNF relies on the activation of phospholipase C, followed by the formation of diacylglycerol, activation of protein kinase C, and the opening of L-type voltage-dependent Ca(2+) channels. We further show that once released by GABA(B) receptor activation, BDNF increases the membrane expression of ß(2/3) -containing GABA(A) receptors in neuronal cultures. These results reveal a novel function of GABA(B) receptors in regulating the expression of GABA(A) receptor through BDNF-tropomyosin-related kinase B receptor dependent signalling pathway.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Receptores de GABA-A/biossíntese , Receptores de GABA-B/fisiologia , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Diglicerídeos/metabolismo , Ensaio de Imunoadsorção Enzimática , Agonistas GABAérgicos/farmacologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imuno-Histoquímica , Microscopia Confocal , Fosfolipase C beta/metabolismo , Fosforilação , Proteína Quinase C/metabolismo , Ratos , Membranas Sinápticas/metabolismo
10.
Eur J Neurosci ; 32(8): 1239-44, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20880359

RESUMO

During the last decade, a major role has emerged for brain-derived neurotrophic factor (BDNF) in the translation of intrinsic or sensory-driven synaptic activities into the neuronal network plasticity that sculpts neural circuits. BDNF is released from dendrites and axons in response to synaptic activity and modulates many aspects of synaptic function. Although the importance of BDNF in synaptic plasticity has been clearly established, direct evidence for a specific contribution of the activity-dependent dendritic secretion of BDNF has been difficult to obtain. This review summarizes recent advances that have established specific effects of postsynaptic BDNF secretion on synapse efficacy and development. We will also discuss these data in the light of their functional and pathological significance.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dendritos/metabolismo , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Animais , Encéfalo/metabolismo , Sinapses/metabolismo
11.
J Neurosci ; 29(37): 11650-61, 2009 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-19759312

RESUMO

GABA, the main inhibitory neurotransmitter in the adult brain, has recently emerged as an important signal in network development. Most of the trophic functions of GABA have been attributed to depolarization of the embryonic and neonatal neurons via the activation of ionotropic GABA(A) receptors. Here we demonstrate a novel mechanism by which endogenous GABA selectively regulates the development of GABAergic synapses in the developing brain. Using whole-cell patch-clamp recordings on newborn mouse hippocampi lacking functional GABA(B) receptors (GABA(B)-Rs) and time-lapse fluorescence imaging on cultured hippocampal neurons expressing GFP-tagged brain-derived neurotrophic factor (BDNF), we found that activation of metabotropic GABA(B) receptors (GABA(B)-Rs) triggers secretion of BDNF and promotes the development of perisomatic GABAergic synapses in the newborn mouse hippocampus. Because activation of GABA(B)-Rs occurs during the characteristic ongoing physiological network-driven synaptic activity present in the developing hippocampus, our results reveal a new mechanism by which synaptic activity can modulate the development of local GABAergic synaptic connections in the developing brain.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Receptores de GABA-B/fisiologia , Sinapses/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Animais Recém-Nascidos , Fator Neurotrófico Derivado do Encéfalo/deficiência , Proteína de Ligação a CREB/metabolismo , Células Cultivadas , Ensaio de Imunoadsorção Enzimática/métodos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Antagonistas GABAérgicos/farmacologia , Proteínas de Fluorescência Verde/genética , Hipocampo/citologia , Lisina/análogos & derivados , Lisina/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Camundongos , Camundongos Knockout , Neurônios/citologia , Técnicas de Patch-Clamp/métodos , Ácidos Fosfínicos/farmacologia , Propanolaminas/farmacologia , Quinoxalinas/farmacologia , Receptores de GABA-B/deficiência , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologia , Valina/análogos & derivados , Valina/farmacologia
12.
Mol Neurobiol ; 39(1): 37-49, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19156544

RESUMO

Network construction and reorganization is modulated by the level and pattern of synaptic activity generated in the nervous system. During the past decades, neurotrophins, and in particular brain-derived neurotrophic factor (BDNF), have emerged as attractive candidates for linking synaptic activity and brain plasticity. Thus, neurotrophin expression and secretion are under the control of activity-dependent mechanisms and, besides their classical role in supporting neuronal survival neurotrophins, modulate nearly all key steps of network construction from neuronal migration to experience-dependent refinement of local connections. In this paper, we provide an overview of recent findings showing that BDNF can serve as a target-derived messenger for activity-dependent synaptic plasticity and development at the single cell level.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dendritos/metabolismo , Potenciais de Ação/fisiologia , Animais , Comunicação Celular/fisiologia , Dendritos/ultraestrutura , Sinapses/metabolismo
13.
J Physiol ; 586(21): 5119-28, 2008 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-18772203

RESUMO

Spontaneous ongoing synaptic activity is thought to play an instructive role in the maturation of the neuronal circuits. However the type of synaptic activity involved and how this activity is translated into structural and functional changes is not fully understood. Here we show that ongoing glutamatergic synaptic activity triggers a long-lasting potentiation of gamma-aminobutyric acid (GABA) mediated synaptic activity (LLP(GABA-A)) in the developing rat hippocampus. LLP(GABA-A) induction requires (i) the activation of AMPA receptors and L-type voltage-dependent calcium channels, (ii) the release of endogenous brain-derived neurotrophic factor (BDNF), and (iii) the activation of postsynaptic tropomyosin-related kinase receptors B (TrkB). We found that spontaneous glutamatergic activity is required to maintain a high level of native BDNF in the newborn rat hippocampus and that application of exogenous BDNF induced LLP(GABA-A) in the absence of glutamatergic activity. These results suggest that ongoing glutamatergic synaptic activity plays a pivotal role in the functional maturation of hippocampal GABAergic synapses by means of a cascade involving BDNF release and downstream signalling through postsynaptic TrkB receptor activation.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/citologia , Sinapses/metabolismo , Ácido gama-Aminobutírico/metabolismo , Potenciais de Ação/fisiologia , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Canais de Cálcio Tipo L/fisiologia , Hipocampo/fisiologia , Ratos , Ratos Wistar , Receptor trkB/fisiologia , Receptores de AMPA/fisiologia , Receptores de GABA-A/fisiologia
14.
J Neurosci ; 28(27): 7013-23, 2008 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-18596175

RESUMO

Brain-derived neurotrophic factor (BDNF) is a major regulator of activity-dependent synapse development and plasticity. Because BDNF is a secreted protein, it has been proposed that BDNF is released from target neurons in an activity-dependent manner. However, direct evidence for postsynaptic release of BDNF triggered by ongoing network activity is still lacking. Here we transfected cultures of dissociated hippocampal neurons with green fluorescent protein (GFP)-tagged BDNF and combined whole-cell recording, time-lapse fluorescent imaging, and immunostaining to monitor activity-dependent dendritic release of BDNF. We found that spontaneous backpropagating action potentials, but not synaptic activity alone, led to a Ca2+-dependent dendritic release of BDNF-GFP. Moreover, we provide evidence that endogenous BDNF released from a single neuron can phosphorylate CREB (cAMP response element-binding protein) in neighboring neurons, an important step of immediate early gene activation. Therefore, together, our results support the hypothesis that BDNF might act as a target-derived messenger of activity-dependent synaptic plasticity and development.


Assuntos
Potenciais de Ação/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dendritos/metabolismo , Hipocampo/crescimento & desenvolvimento , Rede Nervosa/crescimento & desenvolvimento , Plasticidade Neuronal/fisiologia , Animais , Animais Recém-Nascidos , Sinalização do Cálcio/fisiologia , Diferenciação Celular/fisiologia , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dendritos/ultraestrutura , Regulação da Expressão Gênica/genética , Genes Precoces/genética , Proteínas de Fluorescência Verde/genética , Imuno-Histoquímica , Técnicas de Patch-Clamp , Fosforilação , Ratos , Proteínas Recombinantes de Fusão/genética , Coloração e Rotulagem , Transmissão Sináptica/fisiologia , Ativação Transcricional
15.
Commun Integr Biol ; 1(2): 153-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19704877

RESUMO

Brain derived neurotrophic factor (BDNF) is crucial for the formation of appropriate synaptic connections during development and for learning and memory in adults. Secretion of this neurotrophin is under activity-dependent control. Understanding which patterns of physiological activity regulate BDNF secretion is therefore an important step in the comprehension of its role. We have recently shown that back propagation of action potentials (bAPs) is the principal triggering mechanism of dendritic BDNF secretion occurring during ongoing neuronal activity in neuronal cultures. In the present addendum we discuss possible implications of bAPs-induced BDNF secretion on the construction and reorganization of neuronal networks.

16.
J Physiol ; 577(Pt 3): 829-40, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17023506

RESUMO

In the present report, we focused our attention on the role played by the muscarinic acetylcholine receptors (mAChRs) in different forms of long-term synaptic plasticity. Specifically, we investigated long-term potentiation (LTP) and long-term depression (LTD) expression elicited by theta-burst stimulation (TBS) and low-frequency stimulation (LFS), respectively, in visual cortical slices obtained from different mAChR knockout (KO) mice. A normal LTP was evoked in M(1)/M(3) double KO mice, while LTP was impaired in the M(2)/M(4) double KO animals. On the other hand, LFS induced LTD in M(2)/M(4) double KO mice, but failed to do so in M(1)/M(3) KO mice. Interestingly, LFS produced LTP instead of LTD in M(1)/M(3) KO mice. Analysis of mAChR single KO mice revealed that LTP was affected only by the simultaneous absence of both M(2) and M(4) receptors. A LFS-dependent shift from LTD to LTP was also observed in slices from M(1) KO mice, while LTD was simply abolished in slices from M(3) KO mice. Using pharmacological tools, we showed that LTP in control mice was blocked by pertussis toxin, an inhibitor of G(i/o) proteins, but not by raising intracellular cAMP levels. In addition, the inhibition of phospholipase C by U73122 induced the same shift from LTD to LTP after LFS observed in M(1) single KO and M(1)/M(3) double KO mice. Our results indicate that different mAChR subtypes regulate different forms of long-term synaptic plasticity in the mouse visual cortex, activating specific G proteins and downstream intracellular mechanisms.


Assuntos
Plasticidade Neuronal/fisiologia , Receptores Muscarínicos/fisiologia , Sinapses/fisiologia , Córtex Visual/fisiologia , Animais , Estimulação Elétrica/métodos , Eletrofisiologia , Estrenos/farmacologia , Proteínas de Ligação ao GTP/antagonistas & inibidores , Técnicas In Vitro , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/fisiologia , Camundongos , Camundongos Knockout , Toxina Pertussis/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Pirrolidinonas/farmacologia , Receptores Muscarínicos/deficiência , Ritmo Teta , Fosfolipases Tipo C/antagonistas & inibidores
17.
Brain Res ; 1095(1): 43-50, 2006 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-16730341

RESUMO

Despite the evidence that cortical synaptic organization and cognitive functions are influenced by the activity of the cholinergic system during postnatal development, so far no information is available on the effects produced by acetylcholine (ACh) on synaptic transmission. In the present article, we show that the ability of visual cortex slices to respond to ACh depends on postnatal age. In adulthood, ACh exerts mainly a facilitatory action on synaptic transmission, depressing field potential (FP) amplitude only if applied at high concentrations (millimolar range). During early postnatal development, at postnatal day 13 (P13), facilitation by ACh was lacking, with depression of FP observed with concentration of ACh in the micromolar range. The magnitude of ACh facilitatory effects increases with age. The time course of ACh-dependent facilitation overlaps the developmental maturation of acetylcholinesterase (AChE), suggesting a close relationship between ACh action and AChE activity. Thus, age-dependent modification of the cholinergic modulatory action may affect cortical maturation by regulating the magnitude of synaptic transmission.


Assuntos
Acetilcolina/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Córtex Visual/citologia , Córtex Visual/crescimento & desenvolvimento , Acetilcolinesterase/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Atropina/farmacologia , Relação Dose-Resposta a Droga , Interações de Medicamentos , Estimulação Elétrica/métodos , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/efeitos da radiação , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Imuno-Histoquímica/métodos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Antagonistas Muscarínicos/farmacologia , RNA Mensageiro/metabolismo , Receptores Muscarínicos/genética , Receptores Muscarínicos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transmissão Sináptica/fisiologia
18.
J Physiol ; 566(Pt 3): 907-19, 2005 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-15919709

RESUMO

The central cholinergic system plays a crucial role in synaptic plasticity and spatial attention; however, the roles of the individual cholinergic receptors involved in these activities are not well understood at present. In the present study, we show that acetylcholine (ACh) can facilitate or depress synaptic transmission in occipital slices of mouse visual cortex. The precise nature of the ACh effects depends on the ACh concentration, and is input specific, as shown by stimulating different synaptic pathways. Pharmacological blockade of muscarinic receptor (mAChR) subtypes and the use of M1-M5 mAChR-deficient mice showed that specific mAChR subtypes, together with the activity of the cholinesterases (ChEs), mediate facilitation or depression of synaptic transmission. The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli.


Assuntos
Acetilcolina/farmacologia , Potenciais de Ação/fisiologia , Receptores Muscarínicos/metabolismo , Transmissão Sináptica/fisiologia , Córtex Visual/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Muscarínicos/deficiência , Receptores Muscarínicos/genética , Transmissão Sináptica/efeitos dos fármacos , Córtex Visual/efeitos dos fármacos
19.
J Physiol ; 559(Pt 2): 497-506, 2004 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15243137

RESUMO

Nerve growth factor (NGF) has been shown to regulate plasticity in the visual cortex of monocularly deprived animals. However, to date, few attempts have been made to investigate the role of NGF in synaptic plasticity at the cellular level. In the study reported here we looked at the effects of exogenously applied NGF on synaptic plasticity of layer II-III regular spiking (RS) neurones in visual cortex of 16- to 18-day-old rats. We found that local application of NGF converted high frequency stimulation (HFS)-induced long-term potentiation (LTP) into long-term depression (LTD). We showed that this shift of synaptic plasticity was also obtained with bath application of NGF during HFS. Application of NGF subsequent to HFS left LTP unaffected, conferring temporal constraints on NGF efficacy. NGF effects on LTP were mediated by TrkA receptors. Indeed, blockade of TrkA by monoclonal antibody prevented NGF from inducing LTD following HFS. Low frequency stimulation (LFS) elicited LTD in RS cells. We found that NGF or blockade of NGF signalling by anti-TrkA antibody did not change the amplitude of the LTD induced by LFS. Thus, the NGF effect is selective for synaptic modifications induced by HFS in RS cells. The present results indicate that NGF may modulate the sign of long-term changes of synaptic efficacy in response to high frequency inputs.


Assuntos
Potenciação de Longa Duração/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Neurônios/efeitos dos fármacos , Córtex Visual/efeitos dos fármacos , Animais , Técnicas In Vitro , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Neurônios/fisiologia , Ratos , Ratos Wistar , Córtex Visual/fisiologia
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