Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
IBRO Rep ; 9: 195-206, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32944670

RESUMO

The experience of pain involves the activation of multiple brain areas. Pain-specific activity patterns within and between these local networks remain, however, largely unknown. We measured neuronal network oscillations in different relevant regions of the mouse brain during acute pain, induced by subcutaneous injection of capsaicin into the left hind paw. Field potentials were recorded from primary somatosensory cortex, anterior cingulate cortex (ACC), posterior insula, ventral posterolateral thalamic nucleus, parietal cortex, central nucleus of the amygdala and olfactory bulb. Analysis included power spectra of local signals as well as interregional coherences and cross-frequency coupling (CFC). Capsaicin injection caused hypersensitivity to mechanical stimuli for at least one hour. At the same time, CFC between low (1-12 Hz) and fast frequencies (80-120 Hz) was increased in the ACC, as well as interregional coherence of low frequency oscillations (< 30 Hz) between several networks. However, these changes were not significant anymore after multiple comparison corrections. Using a variable selection method (elastic net) and a logistic regression classifier, however, the pain state was reliably predicted by combining parameters of power and coherence from various regions. Distinction between capsaicin and saline injection was also possible when data were restricted to frequencies <30 Hz, as used in clinical electroencephalography (EEG). Our findings indicate that changes of distributed brain oscillations may provide a functional signature of acute pain or pain-related alterations in activity.

2.
Sci Rep ; 8(1): 6432, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29691421

RESUMO

Slow brain oscillations are usually coherent over long distances and thought to link distributed cell assemblies. In mice, theta (5-10 Hz) stands as one of the most studied slow rhythms. However, mice often breathe at theta frequency, and we recently reported that nasal respiration leads to local field potential (LFP) oscillations that are independent of theta. Namely, we showed respiration-coupled oscillations in the hippocampus, prelimbic cortex, and parietal cortex, suggesting that respiration could impose a global brain rhythm. Here we extend these findings by analyzing LFPs from 15 brain regions recorded simultaneously with respiration during exploration and REM sleep. We find that respiration-coupled oscillations can be detected in parallel with theta in several neocortical regions, from prefrontal to visual areas, and also in subcortical structures such as the thalamus, amygdala and ventral hippocampus. They might have escaped attention in previous studies due to the absence of respiration monitoring, the similarity with theta oscillations, and the highly variable peak frequency. We hypothesize that respiration-coupled oscillations constitute a global brain rhythm suited to entrain distributed networks into a common regime. However, whether their widespread presence reflects local network activity or is due to volume conduction remains to be determined.


Assuntos
Encéfalo/fisiologia , Sono REM/fisiologia , Ritmo Teta/fisiologia , Animais , Encéfalo/metabolismo , Eletroencefalografia/métodos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Respiração , Sono/fisiologia
3.
Proc Natl Acad Sci U S A ; 114(17): 4519-4524, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28396398

RESUMO

Theta oscillations (4-12 Hz) are thought to provide a common temporal reference for the exchange of information among distant brain networks. On the other hand, faster gamma-frequency oscillations (30-160 Hz) nested within theta cycles are believed to underlie local information processing. Whether oscillatory coupling between global and local oscillations, as showcased by theta-gamma coupling, is a general coding mechanism remains unknown. Here, we investigated two different patterns of oscillatory network activity, theta and respiration-induced network rhythms, in four brain regions of freely moving mice: olfactory bulb (OB), prelimbic cortex (PLC), parietal cortex (PAC), and dorsal hippocampus [cornu ammonis 1 (CA1)]. We report differential state- and region-specific coupling between the slow large-scale rhythms and superimposed fast oscillations. During awake immobility, all four regions displayed a respiration-entrained rhythm (RR) with decreasing power from OB to CA1, which coupled exclusively to the 80- to 120-Hz gamma subband (γ2). During exploration, when theta activity was prevailing, OB and PLC still showed exclusive coupling of RR with γ2 and no theta-gamma coupling, whereas PAC and CA1 switched to selective coupling of theta with 40- to 80-Hz (γ1) and 120- to 160-Hz (γ3) gamma subbands. Our data illustrate a strong, specific interaction between neuronal activity patterns and respiration. Moreover, our results suggest that the coupling between slow and fast oscillations is a general brain mechanism not limited to the theta rhythm.

4.
J Neurosci ; 36(1): 162-77, 2016 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-26740658

RESUMO

UNLABELLED: We have recently described a slow oscillation in the hippocampus of urethane-anesthetized mice, which couples to nasal respiration and is clearly distinct from co-occurring theta oscillations. Here we set out to investigate whether such type of patterned network activity, which we named "hippocampal respiration rhythm" (HRR), also occurs in awake mice. In freely moving mice, instantaneous respiration rate is extremely variable, and respiration is superimposed by bouts of sniffing. To reduce this variability, we clamped the behavior of the animal to either awake immobility or treadmill running by using a head-fixed setup while simultaneously recording respiration and field potentials from the olfactory bulb (OB) and hippocampus. Head-fixed animals often exhibited long periods of steady respiration rate during either immobility or running, which allowed for spectral and coherence analyses with a sufficient frequency resolution to sort apart respiration and theta activities. We could thus demonstrate the existence of HRR in awake animals, namely, a respiration-entrained slow rhythm with highest amplitude at the dentate gyrus. HRR was most prominent during immobility and running with respiration rates slower than theta oscillations. Nevertheless, HRR could also be faster than theta. Discharges of juxtacellularly recorded cells in CA1 and dentate gyrus were modulated by HRR and theta oscillations. Granger directionality analysis revealed that HRR is caused by the OB and that theta oscillations in OB are caused by the hippocampus. Our results suggest that respiration-coupled oscillations aid the exchange of information between olfactory and memory networks. SIGNIFICANCE STATEMENT: Olfaction is a major sense in rodents. In consequence, the olfactory bulb (OB) should be able to transmit information to downstream regions. Here we report potential mechanisms underlying such information transfer. We demonstrate the existence of a respiration-entrained rhythm in the hippocampus of awake mice. Frequencies of the hippocampal respiration rhythm (HRR) overlap with classical theta oscillations, but both rhythms are clearly distinct. HRR is most prominent in the dentate gyrus, especially when respiration is slower than theta frequency. Discharges of neurons in CA1 and dentate gyrus are modulated by both HRR and theta. Directionality analysis shows that HRR is caused by the OB. Our results suggest that respiration-coupled oscillations aid the exchange of information between olfactory and memory networks.


Assuntos
Relógios Biológicos/fisiologia , Hipocampo/fisiologia , Centro Respiratório/fisiopatologia , Taxa Respiratória/fisiologia , Ritmo Teta/fisiologia , Vigília/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Cell Mol Neurobiol ; 34(6): 777-89, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24798513

RESUMO

Breathing and vigilance are regulated by pH and CO2 levels in the central nervous system. The hypocretin/orexin (Hcrt/Orx)- and histamine (HA)-containing hypothalamic neurons synergistically control different aspects of the waking state. Acidification inhibits firing of most neurons but these two groups in the caudal hypothalamus are excited by hypercapnia and protons, similar to the chemosensory neurons in the brain stem. Activation of hypothalamic wake-on neurons in response to hypercapnia, seen with the c-Fos assay, is supported by patch-clamp recordings in rodent brain slices: Hcrt/Orx and HA neurons are excited by acidification in the physiological range (pH from 7.4 to 7.0). Multiple molecular mechanisms mediate wake-promoting effects of protons in HA neurons in the tuberomamillary nucleus (TMN): among them are acid-sensing ion channels, Na(+),K(+)-ATPase, group I metabotropic glutamate receptors (mGluRI). HA neurons are remarkably sensitive to the mGluRI agonist DHPG (threshold concentration 0.5 µM) and mGluRI antagonists abolish proton-induced excitation of HA neurons. Hcrt/Orx neurons are excited through block of a potassium conductance and release glutamate with their peptides in TMN. The two hypothalamic nuclei and the serotonergic dorsal raphe cooperate toward CO2/acid-induced arousal. Their interactions and molecular mechanisms of H(+)/CO2-induced activation are relevant for the understanding and treatment of respiratory and metabolic disorders related to sleep-waking such as obstructive sleep apnea and sudden infant death syndrome.


Assuntos
Canais Iônicos Sensíveis a Ácido/metabolismo , Potenciais de Ação/fisiologia , Hipotálamo/metabolismo , Neurônios/metabolismo , Animais , Ácido Glutâmico/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neuropeptídeos/metabolismo , Orexinas
6.
J Neurosci ; 34(17): 5949-64, 2014 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-24760854

RESUMO

Different types of network oscillations occur in different behavioral, cognitive, or vigilance states. The rodent hippocampus expresses prominent θ oscillations at frequencies between 4 and 12 Hz, which are superimposed by phase-coupled γ oscillations (30-100 Hz). These patterns entrain multineuronal activity over large distances and have been implicated in sensory information processing and memory formation. Here we report a new type of oscillation at near-θ frequencies (2-4 Hz) in the hippocampus of urethane-anesthetized mice. The rhythm is highly coherent with nasal respiration and with rhythmic field potentials in the olfactory bulb: hence, we called it hippocampal respiration-induced oscillations. Despite the similarity in frequency range, several features distinguish this pattern from locally generated θ oscillations: hippocampal respiration-induced oscillations have a unique laminar amplitude profile, are resistant to atropine, couple differently to γ oscillations, and are abolished when nasal airflow is bypassed by tracheotomy. Hippocampal neurons are entrained by both the respiration-induced rhythm and concurrent θ oscillations, suggesting a direct interaction between endogenous activity in the hippocampus and nasal respiratory inputs. Our results demonstrate that nasal respiration strongly modulates hippocampal network activity in mice, providing a long-range synchronizing signal between olfactory and hippocampal networks.


Assuntos
Ondas Encefálicas/fisiologia , Hipocampo/fisiologia , Neurônios/fisiologia , Respiração , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL
7.
PLoS One ; 7(8): e42512, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22880010

RESUMO

Since ancient times ursodeoxycholic acid (UDCA), a constituent of bile, is used against gallstone formation and cholestasis. A neuroprotective action of UDCA was demonstrated recently in models of Alzheimer's disease and retinal degeneration. The mechanisms of UDCA action in the nervous system are poorly understood. We show now that UDCA promotes wakefulness during the active period of the day, lacking this activity in histamine-deficient mice. In cultured hypothalamic neurons UDCA did not affect firing rate but synchronized the firing, an effect abolished by the GABA(A)R antagonist gabazine. In histaminergic neurons recorded in slices UDCA reduced amplitude and duration of spontaneous and evoked IPSCs. In acutely isolated histaminergic neurons UDCA inhibited GABA-evoked currents and sIPSCs starting at 10 µM (IC(50) = 70 µM) and did not affect NMDA- and AMPA-receptor mediated currents at 100 µM. Recombinant GABA(A) receptors composed of α1, ß1-3 and γ2L subunits expressed in HEK293 cells displayed a sensitivity to UDCA similar to that of native GABA(A) receptors. The mutation α1V256S, known to reduce the inhibitory action of pregnenolone sulphate, reduced the potency of UDCA. The mutation α1Q241L, which abolishes GABA(A)R potentiation by several neurosteroids, had no effect on GABA(A)R inhibition by UDCA. In conclusion, UDCA enhances alertness through disinhibition, at least partially of the histaminergic system via GABA(A) receptors.


Assuntos
Antagonistas de Receptores de GABA-A/farmacologia , Histamina/metabolismo , Receptores de GABA-A/metabolismo , Ácido Ursodesoxicólico/farmacologia , Vigília/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Administração Oral , Animais , Histamina/deficiência , Região Hipotalâmica Lateral/citologia , Região Hipotalâmica Lateral/efeitos dos fármacos , Região Hipotalâmica Lateral/fisiologia , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Cinética , Camundongos , Proteínas Mutantes/metabolismo , Mutação/genética , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Picrotoxina/farmacologia , Receptores de GABA-A/genética , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/metabolismo , Esteroides/farmacologia , Fatores de Tempo , Ácido Ursodesoxicólico/administração & dosagem
8.
Front Syst Neurosci ; 6: 23, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22509157

RESUMO

The histaminergic neurons in the tuberomamillary nucleus (TMN) of the posterior hypothalamus are involved in the control of arousal. These neurons are sensitive to hypercapnia as has been shown in experiments examining c-Fos expression, a marker for increased neuronal activity. We investigated the mechanisms through which TMN neurons respond to changes in extracellular levels of acid/CO(2). Recordings in rat brain slices revealed that acidification within the physiological range (pH from 7.4 to 7.0), as well as ammonium chloride (5 mM), excite histaminergic neurons. This excitation is significantly reduced by antagonists of type I metabotropic glutamate receptors and abolished by benzamil, an antagonist of acid-sensing ion channels (ASICs) and Na(+)/Ca(2+) exchanger, or by ouabain which blocks Na(+)/K(+) ATPase. We detected variable combinations of 4 known types of ASICs in single TMN neurons, and observed activation of ASICs in single dissociated TMN neurons only at pH lower than 7.0. Thus, glutamate, which is known to be released by glial cells and orexinergic neurons, amplifies the acid/CO(2)-induced activation of TMN neurons. This amplification demands the coordinated function of metabotropic glutamate receptors, Na(+)/Ca(2+) exchanger and Na(+)/K(+) ATPase. We also developed a novel HDC-Cre transgenic reporter mouse line in which histaminergic TMN neurons can be visualized. In contrast to the rat, the mouse histaminergic neurons lacked the pH 7.0-induced excitation and displayed only a minimal response to the mGluR I agonist DHPG (0.5 µM). On the other hand, ammonium-induced excitation was similar in mouse and rat. These results are relevant for the understanding of the neuronal mechanisms controlling acid/CO(2)-induced arousal in hepatic encephalopathy and obstructive sleep apnoea. Moreover, the new HDC-Cre mouse model will be a useful tool for studying the physiological and pathophysiological roles of the histaminergic system.

9.
Pflugers Arch ; 463(1): 187-99, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21735059

RESUMO

The histaminergic neurons of the posterior hypothalamus (tuberomamillary nucleus-TMN) control wakefulness, and their silencing through activation of GABA(A) receptors (GABA(A)R) induces sleep and is thought to mediate sedation under propofol anaesthesia. We have previously shown that the ß1 subunit preferring fragrant dioxane derivatives (FDD) are highly potent modulators of GABA(A)R in TMN neurons. In recombinant receptors containing the ß3N265M subunit, FDD action is abolished and GABA potency is reduced. Using rat, wild-type and ß3N265M mice, FDD and propofol, we explored the relative contributions of ß1- and ß3-containing GABA(A)R to synaptic transmission from the GABAergic sleep-on ventrolateral preoptic area neurons to TMN. In ß3N265M mice, GABA potency remained unchanged in TMN neurons, but it was decreased in cultured posterior hypothalamic neurons with impaired modulation of GABA(A)R by propofol. Spontaneous and evoked GABAergic synaptic currents (IPSC) showed ß1-type pharmacology, with the same effects achieved by 3 µM propofol and 10 µM PI24513. Propofol and the FDD PI24513 suppressed neuronal firing in the majority of neurons at 5 and 100 µM, and in all cells at 10 and 250 µM, respectively. FDD given systemically in mice induced sedation but not anaesthesia. Propofol-induced currents were abolished (1-6 µM) or significantly reduced (12 µM) in ß3N265M mice, whereas gating and modulation of GABA(A)R by PI24513 as well as modulation by propofol were unchanged. In conclusion, ß1-containing (FDD-sensitive) GABA(A)R represent the major receptor pool in TMN neurons responding to GABA, while ß3-containing (FDD-insensitive) receptors are gated by low micromolar doses of propofol. Thus, sleep and anaesthesia depend on different GABA(A)R types.


Assuntos
Anestesia , Subunidades Proteicas/fisiologia , Receptores de GABA-A/fisiologia , Sono/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Fenômenos Eletrofisiológicos/fisiologia , Agonistas de Receptores de GABA-A/farmacologia , Expressão Gênica/genética , Histamina/metabolismo , Região Hipotalâmica Lateral/citologia , Região Hipotalâmica Lateral/metabolismo , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/fisiologia , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/fisiologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Mutação Puntual/fisiologia , Propofol/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/genética , Ácido gama-Aminobutírico/farmacologia
10.
J Physiol ; 589(Pt 6): 1349-66, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21242252

RESUMO

L-Dopa is the most effective treatment of early and advanced stages of Parkinson's disease (PD), but its chronic use leads to loss of efficiency and dyskinesia. This is delayed by lower dosage at early stages, made possible by additional treatment with histamine antagonists. We present here evidence that histaminergic tuberomamillary nucleus (TMN) neurons, involved in the control of wakefulness, are excited under L-Dopa (EC50 15 µM), express Dopa decarboxylase and show dopamine immunoreactivity. Dopaergic excitation was investigated with patch-clamp recordings from brain slices combined with single-cell RT-PCR analysis of dopamine receptor expression. In addition to the excitatory dopamine 1 (D1)-like receptors, TMN neurons express D2-like receptors, which are coupled through phospholipase C (PLC) to transient receptor potential canonical (TRPC) channels and the Na+/Ca2+ exchanger. D2 receptor activation enhances firing frequency, histamine release in freely moving rats (microdialysis) and wakefulness (EEG recordings). In histamine deficient mice the wake-promoting action of the D2 receptor agonist quinpirole (1 mg kg⁻¹, I.P.) is missing. Thus the histamine neurons can, subsequent to L-Dopa uptake, co-release dopamine and histamine from their widely projecting axons. Taking into consideration the high density of histaminergic fibres and the histamine H3 receptor heteromerization either with D1 or with D2 receptors in the striatum, this study predicts new avenues for PD therapy.


Assuntos
Histamina/metabolismo , Região Hipotalâmica Lateral/efeitos dos fármacos , Região Hipotalâmica Lateral/metabolismo , Levodopa/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Animais , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Camundongos , Camundongos Knockout , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo
11.
Prog Brain Res ; 160: 245-59, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17499118

RESUMO

Presynaptic receptors provide plasticity to GABAergic synapses in the basal ganglia network, in which GABA neurons outnumber all other neurons. Presynaptic receptors, mostly of the metabotropic type, enhance or reduce the strength of synaptic inhibition and are activated by ligands being released from the GABA terminals themselves (autoreceptors) or by ligands coming from other sources (heteroreceptors), including the target neurons innervated by the GABA terminals. The latter mechanism, termed retrograde signaling, is given particular emphasis as far as it occurs in substantia nigra.


Assuntos
Gânglios da Base/fisiologia , Vias Neurais/fisiologia , Terminações Pré-Sinápticas/fisiologia , Receptores de GABA-B/fisiologia , Ácido gama-Aminobutírico/fisiologia , Animais , Autorreceptores/fisiologia , Gânglios da Base/anatomia & histologia , Retroalimentação/fisiologia , Humanos , Inibição Neural/fisiologia , Vias Neurais/anatomia & histologia , Transmissão Sináptica/fisiologia
12.
J Physiol ; 577(Pt 3): 879-90, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17053035

RESUMO

A phasic activation of small-conductance Ca(2+)-dependent K(+) channels (SK channels) underlies spike-afterhyperpolarizations and spike-independent, transient hyperpolarizations in juvenile substantia nigra neurons. Outward current pulses that cause the spike-independent hyperpolarizations result from ryanodine receptor-mediated Ca(2+) release from intracellular stores. To study the modulation of excitability by the outward current pulses, we recorded from GABAergic pars reticulata neurons of mice at postnatal days 12-16. We induced a prolongation of SK channel open states by 1-ethyl-2-benzimidazolinone (1-EBIO). In addition to a prolongation of spike-afterhyperpolarizations, 1-EBIO (200 microm) potentiated outward current pulses by increasing their duration. Neurons were manipulated by current injection to display continuous or discontinuous discharge. Despite the prolongation of the outward current pulses by 1-EBIO, continuous action potential discharge became more regular, although its frequency declined. Durations of silent periods (periods of >2x average interspike interval) increased. Caffeine (1 mm) further increased the duration of such silent periods. Caffeine, however, had no effect at short interspike intervals (<600 ms). Cyclopiazonic acid (10 microm) silenced discharge in 1-EBIO, but discharge reappeared with the depletion of Ca(2+) stores. We conclude that the modulation of excitability by an activation of SK channels through ryanodine receptor-mediated release of Ca(2+) critically depends on the frequency of discharge. Outward current pulses occur only if interspike intervals exceed the duration of spike-afterhyperpolarizations. In this instance, the phasic, spike-independent activation of SK channels supports pauses to interrupt autonomous discharge in juvenile GABAergic pars reticulata neurons.


Assuntos
Cálcio/metabolismo , Neurônios/fisiologia , Substância Negra/fisiologia , Ácido gama-Aminobutírico/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Benzimidazóis/farmacologia , Cafeína/farmacologia , Agonistas dos Canais de Cálcio/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulação Elétrica , Eletrofisiologia , Indóis/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Baixa/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Substância Negra/citologia , Substância Negra/metabolismo , Fatores de Tempo
13.
Epilepsy Res ; 52(3): 263-73, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12536059

RESUMO

Inhibition by GABA(B) receptors comprises activation of K(+) conductance and inhibition of Ca(2+) conductance, thereby reducing action potential dependent transmitter release and silencing neuronal activity. We compared epileptiform activity and its inhibition by the activation of GABA(B) receptors in homozygous weaver (wv/wv) and wild type (+/+) CA3 neurons disinhibited by GABA(A) receptor blockade. In wv/wv mice GABA(B) receptors have lost their ability to activate K(+) conductance (J. Neurosci. 18 (1998) 4001). Spontaneous synchronous burst discharges in elevated [K(+)](o) displayed only subtle differences in +/+ and wv/wv slices, except that the GABA(B) receptor agonist R-baclofen in low concentration (0.1 microM) strongly reduced the frequency of synchronous bursts in +/+ CA3 neurons, but not in wv/wv CA3 neurons. A high affinity GABA(B) antagonist, CGP55845A (0.5 microM) promoted the incidence of bursts in low [K(+)](o). Concentration dependence of the reduction of evoked EPSCs was identical in wv/wv and +/+ neurons (IC(50)=0.3 microM). Amplitudes of evoked IPSCs were reduced by 0.01 microM R-baclofen in +/+, but not in wv/wv CA3 neurons. The effect of the low concentration was abolished by Ba(2+), which is known to block Kir conductance. The data suggest that activation of Kir conductance is important for the control of GABA release by GABA(B) autoreceptors in the CA3 network. We conclude that the loss of a contribution of Kir conductance to GABA(B) receptor-mediated autoinhibition reduces the inclination towards spontaneous bursts of wv/wv CA3 pyramidal neurons.


Assuntos
Baclofeno/farmacologia , Epilepsia/prevenção & controle , Agonistas GABAérgicos/farmacologia , Hipocampo/fisiopatologia , Células Piramidais/fisiologia , Receptores de GABA-B/fisiologia , Animais , Bicuculina/farmacologia , Cruzamentos Genéticos , Modelos Animais de Doenças , Feminino , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos , Camundongos Mutantes Neurológicos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Células Piramidais/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...