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1.
J Neurosci ; 36(13): 3676-90, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-27030754

RESUMO

Precise information flow during mnemonic and executive tasks requires the coactivation of adult prefrontal and hippocampal networks in oscillatory rhythms. This interplay emerges early in life, most likely as an anticipatory template of later cognitive performance. At neonatal age, hippocampal theta bursts drive the generation of prefrontal theta-gamma oscillations. In the absence of direct reciprocal interactions, the question arises of which feedback mechanisms control the early entrainment of prefrontal-hippocampal networks. Here, we demonstrate that prefrontal-hippocampal activity couples with discontinuous theta oscillations and neuronal firing in both lateral entorhinal cortex and ventral midline thalamic nuclei of neonatal rats. However, these two brain areas have different contributions to the neonatal long-range communication. The entorhinal cortex mainly modulates the hippocampal activity via direct axonal projections. In contrast, thalamic theta bursts are controlled by the prefrontal cortex via mutual projections and contribute to hippocampal activity. Thus, the neonatal prefrontal cortex modulates the level of hippocampal activation by directed interactions with the ventral midline thalamus. Similar to the adult task-related communication, theta-band activity ensures the feedback control of long-range coupling in the developing brain. SIGNIFICANCE STATEMENT: Memories are encoded by finely tuned interactions within large-scale neuronal networks. This cognitive performance is not inherited, but progressively matures in relationship with the establishment of long-range coupling in the immature brain. The hippocampus initiates and unidirectionally drives the oscillatory entrainment of neonatal prefrontal cortex, yet feedback interactions that precisely control this early communication are still unresolved. Here, we identified distinct roles of entorhinal cortex and ventral midline thalamus for the functional development of prefrontal-hippocampal interactions. While entorhinal oscillations modulate the hippocampal activity by timing the neuronal firing via monosynaptic afferents, thalamic nuclei act as a relay station routing prefrontal activation back to hippocampus. Understanding the mechanisms of network maturation represents the prerequisite for assessing circuit dysfunction in neurodevelopmental disorders.


Assuntos
Mapeamento Encefálico , Córtex Entorrinal/fisiologia , Hipocampo/fisiologia , Vias Neurais/fisiologia , Córtex Pré-Frontal/fisiologia , Tálamo/fisiologia , Potenciais de Ação , Análise de Variância , Animais , Animais Recém-Nascidos , Masculino , Neurônios/fisiologia , Córtex Pré-Frontal/lesões , Ratos , Ratos Wistar , Estilbamidinas/metabolismo , Tálamo/lesões , Fatores de Tempo
2.
J Neurosci ; 33(30): 12510-8, 2013 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-23884954

RESUMO

Dendritic spines are a major substrate of brain plasticity. Although many studies have focused on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-mediated regulation of spine dynamics and synaptic function in adult brain, much less is know about protein kinase A (PKA)-dependent regulation of spine shape dynamics during postnatal brain development. Synaptopodin is a dendritic spine associated modulator of actin dynamics and a substrate of PKA. Here we show that NMDA and cAMP-induced dendritic spine expansion is impaired in hippocampal slices from 15- and 21-d-old synaptopodin-deficient mice. We further show that synaptopodin is required for full expression of PKA-dependent hippocampal long-term potentiation in 15- and 21-d-old, but not adult, mice. PKA-induced cAMP response element-binding phosphorylation is normal in the hippocampus of synaptopodin-deficient mice, suggesting that synaptopodin functions independently of cAMP response element-binding. Our results identify synaptopodin as a substrate of PKA in hippocampal neurons and point to an essential role for synaptopodin in activity-dependent regulation of dendritic spine dynamics and synaptic plasticity in postnatal brain development.


Assuntos
Espinhas Dendríticas/fisiologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Proteínas dos Microfilamentos/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , AMP Cíclico/metabolismo , AMP Cíclico/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Eletrofisiologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Isoquinolinas/farmacologia , Potenciação de Longa Duração/fisiologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/genética , N-Metilaspartato/farmacologia , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Especificidade por Substrato , Sulfonamidas/farmacologia
3.
J Neurosci ; 31(49): 17955-70, 2011 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-22159110

RESUMO

The cholinergic drive enhances input processing in attentional and mnemonic context by interacting with the activity of prefrontal-hippocampal networks. During development, acetylcholine modulates neuronal proliferation, differentiation, and synaptic plasticity, yet its contribution to the maturation of cognitive processing resulting from early entrainment of neuronal networks in oscillatory rhythms remains widely unknown. Here we show that cholinergic projections growing into the rat prefrontal cortex (PFC) toward the end of the first postnatal week boost the generation of nested gamma oscillations superimposed on discontinuous spindle bursts by acting on functional muscarinic but not nicotinic receptors. Although electrical stimulation of cholinergic nuclei increased the occurrence of nested gamma spindle bursts by 41%, diminishment of the cholinergic input by either blockade of the receptors or chronic immunotoxic lesion had the opposite effect. This activation of locally generated gamma episodes by direct cholinergic projections to the PFC was accompanied by indirect modulation of underlying spindle bursts via cholinergic control of hippocampal theta activity. With ongoing maturation and switch of network activity from discontinuous bursts to continuous theta-gamma rhythms, accumulating cholinergic projections acting on both muscarinic and nicotinic receptors mediated the transition from high-amplitude slow to low-amplitude fast rhythms in the PFC. By exerting multiple actions on the oscillatory entrainment of developing prefrontal-hippocampal networks, the cholinergic input may refine them for later gating processing in executive and mnemonic tasks.


Assuntos
Colinérgicos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hipocampo/crescimento & desenvolvimento , Vias Neurais/fisiologia , Córtex Pré-Frontal/crescimento & desenvolvimento , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Anticorpos Monoclonais/farmacologia , Colina O-Acetiltransferase/metabolismo , Estimulação Elétrica , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Masculino , Proteínas do Tecido Nervoso/metabolismo , Vias Neurais/efeitos dos fármacos , Neurônios/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/efeitos dos fármacos , Gravidez , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Proteínas Inativadoras de Ribossomos Tipo 1/farmacologia , Saporinas , Ácido gama-Aminobutírico/metabolismo
4.
Neuropharmacology ; 52(1): 46-54, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16899259

RESUMO

Hippocampal long-term depression (LTD) comprises a persistent reduction of synaptic strength that is typically induced by low frequency stimulation (LFS). Although LTD has been described for the dentate gyrus in vitro, this phenomenon in the dentate gyrus of the intact animal is less well understood. In the current study, we investigated the contribution of NMDA receptors, L-type voltage gated calcium channels and protein synthesis to LFS-induced LTD in the dentate gyrus of freely moving rats. Animals were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. LTD persisted for at least 24h, and was unaffected by prior treatment with the NMDA receptor antagonists AP5 or ifenprodil, which, in contrast, prevented LTP. Neither the L-type voltage-gated calcium channel antagonist, methoxyverapamil, nor the protein translation inhibitors, anisomycin or emetine had an effect on the profile of LTD. Our results suggest that NMDA receptors and L-type voltage-gated calcium channels are not involved in the induction of LTD in the dentate gyrus in vivo. Intriguingly, persistent LTD can be established without the synthesis of new proteins, suggesting that in the dentate gyrus, alternative mechanisms exist for the sustainment of enduring LTD.


Assuntos
Canais de Cálcio Tipo L/fisiologia , Giro Denteado/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Anisomicina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Estimulação Elétrica/métodos , Emetina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Galopamil/farmacologia , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/efeitos da radiação , Masculino , Piperidinas/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo , Vigília
5.
Prog Brain Res ; 163: 473-500, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17765734

RESUMO

This chapter compares the cellular mechanisms that have been implicated in the induction and expression of long-term depression (LTD) at Schaffer collateral-CA1 synapses to perforant path-dentate gyrus (DG) synapses. In general, Schaffer collateral LTD and long-term potentiation (LTP) both appear to be a complex combination of many alterations in synaptic transmission that occur at both presynaptic and postsynaptic sites, while at perforant path synapses, most evidence has focused on postsynaptic long-term alterations. Within the DG, the medial perforant path is far more studied than lateral perforant path synapses, where most evidence relates to the induction of heterosynaptic LTD at lateral perforant path synapses when LTP is induced in the medial perforant path. Of course, there remain many other classes of synapses in the DG where synaptic plasticity, including LTD, have been largely neglected. It is clear that a better understanding of the range of DG loci where long-lasting activity-dependent plasticity, both LTD and LTP, are expressed will be essential to improve our understanding of the cognitive roles of such DG plasticity.


Assuntos
Hipocampo/citologia , Depressão Sináptica de Longo Prazo/fisiologia , Via Perfurante/fisiologia , Sinapses/fisiologia , Animais , Hipocampo/fisiologia , Modelos Biológicos , Via Perfurante/citologia , Transmissão Sináptica
6.
Neuropharmacology ; 49 Suppl 1: 1-12, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16084931

RESUMO

Long term depression (LTD) can be induced by low frequency stimulation (LFS) as well as by agonist activation of neurotransmitter receptors. Group II metabotropic glutamate receptors (mGluRs) play an essential role in the regulation of electrically-induced LTD in the hippocampus in vivo: LTD is inhibited by antagonists, and enhanced by agonists of group II mGluRs. Here we investigated induction of LTD by activation of group II mGluRs as well as the cellular mechanisms which might mediate group II mGluR-induced LTD. Rats were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. Drug application was made through a cannula implanted into the ipsilateral cerebral ventricle. LTD could be induced by agonist activation of either group II mGluRs, or the group II mGluR subtype, mGluR3. Both, group II mGluR-induced LTD and mGluR3-induced LTD were not abolished by mRNA/protein synthesis inhibition. Furthermore, mGluR3-induced LTD was not inhibited by NMDA receptor antagonists or altered by L-type voltage-gated calcium channel blockers. Our data suggest that sole activation of group II mGluRs can mediate LTD in vivo. Intriguingly, this form of LTD is not dependent on protein synthesis or activation of NMDA receptors.


Assuntos
Giro Denteado/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Análise de Variância , Animais , Anisomicina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Giro Denteado/efeitos dos fármacos , Giro Denteado/efeitos da radiação , Dipeptídeos/farmacologia , Interações Medicamentosas , Estimulação Elétrica/métodos , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Lateralidade Funcional/efeitos dos fármacos , Lateralidade Funcional/fisiologia , Lateralidade Funcional/efeitos da radiação , Glicina/análogos & derivados , Glicina/farmacologia , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/efeitos da radiação , Masculino , Fármacos Neuroprotetores/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Wistar , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Fatores de Tempo , Verapamil/farmacologia
7.
Brain Res ; 938(1-2): 22-8, 2002 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-12031531

RESUMO

In this paper we show that gamma oscillations can be elicited by brief (< or = 200 ms) local applications of glutamate in the dentate gyrus of rat hippocampal slices. Dentate gamma oscillations show an initial peak frequency of approximately 70 Hz and last for up to 4 min. The network activity involves functional GABA(A) receptors as it is drastically reduced by GABA(A) receptor antagonists. The oscillations can be observed in the whole dentate gyrus-CA3-network and are coherent between the dentate gyrus and area CA3 for variable periods. Thus, long-lasting gamma oscillations can be experimentally induced in the dentate gyrus and are propagated into the hippocampus proper.


Assuntos
Giro Denteado/efeitos dos fármacos , Giro Denteado/fisiologia , Ácido Glutâmico/farmacologia , Animais , Feminino , Ácido Glutâmico/fisiologia , Hipocampo/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Ratos , Ratos Wistar
8.
Neuron ; 71(2): 332-47, 2011 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-21791291

RESUMO

The coactivation of prefrontal and hippocampal networks in oscillatory rhythms is critical for precise information flow in mnemonic and executive tasks, yet the mechanisms governing its development are still unknown. Here, we demonstrate that already in neonatal rats, patterns of discontinuous oscillatory activity precisely entrain the firing of prefrontal neurons and have distinct spatial and temporal organization over cingulate and prelimbic cortices. Moreover, we show that hippocampal theta bursts drive the generation of neonatal prefrontal oscillations by phase-locking the neuronal firing via axonal pathways. Consequently, functional impairment of the hippocampus reduces the prefrontal activity. With ongoing maturation continuous theta-gamma oscillations emerge and mutually entrain the prejuvenile prefrontal-hippocampal networks. Thus, theta-modulated communication within developing prefrontal-hippocampal networks may be relevant for circuitry refinement and maturation of functional units underlying information storage at adulthood.


Assuntos
Potenciais de Ação/fisiologia , Relógios Biológicos/fisiologia , Hipocampo/citologia , Neurônios/fisiologia , Córtex Pré-Frontal/citologia , Potenciais de Ação/efeitos dos fármacos , Fatores Etários , Aminoácidos , Análise de Variância , Anestésicos Locais/farmacologia , Animais , Animais Recém-Nascidos , Relógios Biológicos/efeitos dos fármacos , Estimulação Elétrica/métodos , Análise de Fourier , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Hipocampo/crescimento & desenvolvimento , Hipocampo/lesões , Lidocaína/farmacologia , N-Metilaspartato/toxicidade , Vias Neurais/efeitos dos fármacos , Vias Neurais/crescimento & desenvolvimento , Neurônios/efeitos dos fármacos , Parvalbuminas/metabolismo , Córtex Pré-Frontal/crescimento & desenvolvimento , Córtex Pré-Frontal/lesões , Ratos
9.
Cereb Cortex ; 15(9): 1414-23, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15635057

RESUMO

Group II metabotropic glutamate receptors (mGluRs) play an important role in the regulation of hippocampal synaptic plasticity in vivo: long-term potentiation (LTP) is inhibited and long-term depression (LTD) is enhanced by activation of these receptors. The contribution, in vivo, of the individual group II mGluR subtypes has not been characterized. We analysed the involvement of the subtype mGluR3 in LTD and LTP. Rats were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. Neither the selective mGluR3 agonist, N-acetylaspartylglutamate (NAAG), nor the antagonist beta-NAAG, given intracerebrally, affected basal synaptic transmission. beta-NAAG significantly inhibited LTD expression. NAAG exhibited transient inhibitory effects on the intermediate phase of LTD. Whereas NAAG altered paired-pulse responses, beta-NAAG had no effect, suggesting that antagonism of mGluR3 prevents LTD via a postsynaptic mechanism, whereas agonist activation of mGluR3 modulates LTD at a presynaptic locus. NAAG impaired the expression of LTP, whereas beta-NAAG had no effect. NAAG effects on LTP were blocked by EGLU, a selective group II mGluR antagonist. Our data suggest an essential role for mGluR3 in LTD, and a modulatory role for mGluR3 in LTP, with effects being mediated by distinct pre- and post-synaptic loci.


Assuntos
Hipocampo/fisiologia , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Animais , Giro Denteado/citologia , Giro Denteado/efeitos dos fármacos , Giro Denteado/fisiologia , Potenciais Evocados Visuais/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Memória/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/efeitos dos fármacos
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