RESUMO
Much evidence implicates the serotonergic regulation of the amygdala in anxiety. Thus the present study was undertaken to characterize the influence of serotonin (5-HT) on principal neurons (PNs) of the rat lateral amygdala (LA), using whole cell recordings in vitro. Because inhibition is a major determinant of PN activity, we focused on the control of GABAergic transmission by 5-HT. IPSCs were elicited by local electrical stimulation of LA in the presence of glutamate receptor antagonists. We found that 5-HT reduces GABAA inhibitory postsynaptic currents (IPSCs) via presynaptic 5-HT1B receptors. While the presynaptic inhibition of GABA release also attenuated GABAB currents, this effect was less pronounced than for GABAA currents because 5-HT also induced a competing postsynaptic enhancement of GABAB currents. That is, GABAB currents elicited by pressure application of GABA or baclofen were enhanced by 5-HT. In addition, we obtained evidence suggesting that 5-HT differentially regulates distinct subsets of GABAergic synapses. Indeed, GABAA IPSCs were comprised of two components: a relatively 5-HT-insensitive IPSC that had a fast time course and a 5-HT-sensitive component that had a slower time course. Because the relative contribution of these two components varied depending on whether neurons were recorded at proximity versus at a distance from the stimulating electrodes, we speculate that distinct subtypes of local-circuit cells contribute the two contingents of GABAergic synapses. Overall, our results indicate that 5-HT is a potent regulator of synaptic inhibition in LA.NEW & NOTEWORTHY We report that 5-HT, acting via presynaptic 5-HT1B receptors, attenuates GABAA IPSCs by reducing GABA release in the lateral amygdala (LA). In parallel, 5-HT enhances GABAB currents postsynaptically, such that GABAB inhibitory postsynaptic currents (IPSCs) are relatively preserved from the presynaptic inhibition of GABA release. We also found that the time course of 5-HT-sensitive and -insensitive GABAA IPSCs differ. Together, these results indicate that 5-HT is a potent regulator of synaptic inhibition in LA.
Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Receptor 5-HT1B de Serotonina/metabolismo , Receptores de GABA-A/metabolismo , Receptores de GABA-B/metabolismo , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Estimulação Elétrica , Feminino , Masculino , Técnicas de Patch-Clamp , Ratos , Ratos WistarRESUMO
Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism.
Assuntos
Córtex Cerebral/patologia , Depressão/patologia , Depressão/terapia , Células Piramidais/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Análise de Variância , Animais , Antidepressivos Tricíclicos/farmacologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Estimulação Elétrica , Eletrofisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Proteínas de Arcabouço Homer , Imipramina/farmacologia , Resposta de Imobilidade Tônica/efeitos dos fármacos , Resposta de Imobilidade Tônica/fisiologia , Técnicas In Vitro , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Recuperação de Função Fisiológica/efeitos dos fármacos , Natação/psicologia , Fatores de TempoRESUMO
Feelings of deliciousness during having foods are mainly produced by perceptions of sensory information extracted from foods themselves, such as taste and olfaction. However, environmental factors might modify the feeling of deliciousness. In the present study, we investigated how the condition of audio-visual environments affects the feeling of deliciousness during having sweet foods. Electroencephalograms (EEGs) were recorded from the frontal region of the scalp of healthy participants under virtual scenes of tearoom and construction work, respectively. The participants were asked to rate deliciousness after the recordings. Frequency analyses were performed from the EEGs. During having the foods, occupancy rates of beta frequency band between tearoom scenes and construction work scenes were markedly different, but not in other frequency bands. During having no food, in contrast, there was no difference of occupancy rates in respective frequency bands between the two different scenes. With regard to deliciousness during having sweet foods, all participants rated high scores under the scenes of tearoom than those under the scenes of construction work. Interestingly, there is a positive correlation between occupancy rates of beta frequency band and scores of deliciousness. These findings suggest that comfortable audio-visual environments play an important role in increasing the feeling of deliciousness during having sweet foods, in which beta frequency rhythms may be concerned with producing comprehensive feelings of deliciousness.
Assuntos
Ritmo beta , Emoções/fisiologia , Meio Ambiente , Lobo Frontal/fisiologia , Percepção Gustatória/fisiologia , Estimulação Acústica , Adulto , Percepção Auditiva/fisiologia , Sacarose Alimentar , Alimentos , Humanos , Estimulação Luminosa , Percepção Visual/fisiologiaRESUMO
Tooth and tooth-related organs play important roles in not only mastication, but also sensory perception in the oral region. In general, sensory neural inputs during the developmental period are required for the maturation of functions in the sensory cortex. However, whether maturations of oral somatosensory cortex (OSC) require certain levels of sensory input from oral regions has been unclear. The present study investigated the influence of multiple tooth-losses during the developmental period on age-dependent emergence of rhythmic activities of population neurons in the OSC. Low-frequency electrical stimulation was delivered to layer IV and field potentials were recorded from layer II/III in the OSC of rat brain slices. In control rats, N-methyl-d-aspartate (NMDA) receptor-dependent oscillation at 8-10 Hz appeared during postnatal weeks 2-3. In rats with extraction of multiple teeth at 17-18 days old, oscillation did not appear even at maturity, whereas in rats with multiple teeth extracted at 37-38 days old, oscillation appearances were maintained in maturity. Thus, emergence of oscillation in the OSC was suppressed by multiple tooth-losses during postnatal 2-3 weeks. These results suggest that sufficient neural inputs from the teeth and tooth-related organs during developmental periods are essential for maturation of neural functions in the OSC.
Assuntos
Relógios Biológicos/fisiologia , Neurônios/fisiologia , Córtex Somatossensorial/crescimento & desenvolvimento , Distúrbios Somatossensoriais/etiologia , Perda de Dente/complicações , Dente/crescimento & desenvolvimento , Potenciais de Ação/fisiologia , Vias Aferentes/crescimento & desenvolvimento , Vias Aferentes/fisiopatologia , Envelhecimento/fisiologia , Animais , Denervação , Estimulação Elétrica , Plasticidade Neuronal/fisiologia , Técnicas de Cultura de Órgãos , Ratos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Córtex Somatossensorial/fisiopatologia , Distúrbios Somatossensoriais/fisiopatologia , Dente/inervação , Nervo Trigêmeo/crescimento & desenvolvimento , Nervo Trigêmeo/fisiopatologiaRESUMO
To investigate how pheromonal information is processed in the rat accessory olfactory bulb, we optically imaged intrinsic signals to obtain high-resolution maps of activation induced by urinary stimulation. Application of volatile components in male urine mainly induced activation in the anterior accessory olfactory bulb, irrespective of the sex, whereas volatile female urine elicited activation not only in the anterior but also to some extent in the caudal part of the posterior accessory olfactory bulb of male, but not female, rats. Nonvolatile components of both male and female urine induced activation mainly in the rostral part of the posterior and to a lesser extent in the anterior accessory olfactory bulb, irrespective of the sex. These results indicate that volatile and nonvolatile urinary components activate the anterior and posterior subdivisions of the accessory olfactory bulb, respectively.
Assuntos
Bulbo Olfatório/fisiologia , Feromônios/fisiologia , Urina/fisiologia , Animais , Feminino , Masculino , Bulbo Olfatório/anatomia & histologia , Óptica e Fotônica , Ratos , Ratos Wistar , Fatores Sexuais , Urina/químicaRESUMO
Cyclic AMP (cAMP) is a key intracellular second messenger, and the intracellular cAMP signaling pathway acts to modulate various brain functions. We have previously reported that low-frequency insular cortex stimulation in rat brain slices switches on a voltage oscillator in the parietal cortex that delivers signals horizontally back and forth under caffeine application. The oscillatory activities are N-methyl-D-aspartate (NMDA) receptor-dependent, and the role of oscillation is to strengthen functional intercortical connections. The present study investigated actions of the cAMP signaling pathway on caffeine-induced strengthening of intercortical connections and tried to confirm the role of oscillation on intercortical strengthening by focusing on the cAMP pathway. After induction of parietal oscillation by insular cortex stimulation in caffeine-containing medium, application of membrane-permeable cAMP analog, bromo-cAMP, diminished oscillatory signal delivery from the parietal cortex, but initial insulo-parietal signal propagation remained strong. When oscillatory activities were reduced with co-application of caffeine and bromo-cAMP from the beginning, initial insulo-parietal propagation was established, but amplitudes of propagating wavelets and propagating velocity were reduced. Thus, cAMP-dependent diminution of caffeine-induced NMDA-receptor-dependent oscillatory signal delivery causes attenuation of intercortical strengthening of horizontal pathways between insular and parietal cortices. This finding suggests that the intracellular cAMP signaling pathway has the ability to regulate extracellular communications at the network level, and also that full expression of strengthened intercortical signal communication requires sufficient NMDA-receptor-dependent oscillatory neural activities.
Assuntos
Potenciais de Ação/fisiologia , Relógios Biológicos/fisiologia , Córtex Cerebral/fisiologia , AMP Cíclico/fisiologia , Vias Neurais/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/efeitos da radiação , Animais , Animais Recém-Nascidos , Relógios Biológicos/efeitos dos fármacos , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/efeitos da radiação , Interações Medicamentosas , Estimulação Elétrica/métodos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Técnicas In Vitro , Vias Neurais/efeitos dos fármacos , Vias Neurais/efeitos da radiação , Ratos , Ratos Wistar , Rodanina/análogos & derivados , Tiazolidinas , Fatores de TempoRESUMO
Generation and propagation of oscillatory activities in cortical networks are important features of the brain. However, many issues related to oscillatory phenomena are unclear. We previously reported neocortical oscillation following caffeine treatment of rat brain slices. Input to the primary visual cortex (Oc1) generates N-methyl-d-aspartate (NMDA) receptor-dependent oscillations, and we proposed that the oscillatory signals originate in the secondary visual cortex (Oc2). Because non-NMDA and NMDA receptors cooperate in synaptic transmission, non-NMDA receptors may also play an important role in oscillatory activities. Here we investigated how non-NMDA receptor activities contribute to NMDA receptor-dependent oscillations by using optical recording methods. After induction of stable oscillations with caffeine application, blockade of NMDA receptors abolished the late stable oscillatory phase, but elicited 'hidden' non-NMDA receptor-dependent oscillation during the early depolarizing phase. An interesting finding is that the origin of the non-NMDA receptor-dependent oscillation moved from the Oc1, during the early phase, toward the origin of the NMDA receptor-dependent oscillation that is fixed in the Oc2. In addition, the frequency of the non-NMDA receptor-dependent oscillation was higher than that of the NMDA receptor-dependent oscillation. Thus, in one course of spatiotemporal oscillatory activities, the relative balance in receptor activities between non-NMDA and NMDA receptors gradually changes, and this may be due to the different kinetics of the two receptor types. These results suggest that interplay between the two receptor types in the areas of Oc1 and Oc2 may play an important role in oscillatory signal communication.
Assuntos
Relógios Biológicos/efeitos dos fármacos , Relógios Biológicos/fisiologia , Cafeína/farmacologia , Receptores de N-Metil-D-Aspartato/fisiologia , Córtex Visual/efeitos dos fármacos , Córtex Visual/fisiologia , Animais , Masculino , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/agonistas , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologiaRESUMO
Emergence of oscillatory signal flows between the primary visual cortex (Oc1) and medial secondary visual cortex (Oc2M) was previously dynamically demonstrated in rat brain slices by us. Applying caffeine, a neural modulator, to the slices and using optical recording methods revealed this facilitation along horizontal intrinsic pathways in which initial forward propagation from Oc1 to Oc2M was dependent on both N-methyl-D-aspartate receptors (NMDARs) and non-NMDARs. Conversely, oscillatory backward propagation from Oc2M to Oc1 was entirely dependent on NMDARs. The present study examined: (1) whether the signal behavior between Oc1 and lateral secondary visual cortex (Oc2L) is based on the same mechanism with that between Oc1 and Oc2M; and (2) how non-NMDAR and NMDAR activities underlie opening of horizontal corticocortical pathways between Oc1 and Oc2. Under NMDAR blockade, signals elicited in the Oc1 either could not or only weakly penetrated the Oc2L, even in caffeine-containing medium. In contrast, once forward propagation from Oc1 to Oc2L and oscillatory backward propagation from Oc2L to Oc1 was established in caffeine-containing medium, signals elicited in Oc1 could strongly penetrate the Oc2 even during blockade of NMDA activities, when forward penetrating components were dependent on non-NMDARs. These findings suggest that: (1) signal behavior and its mechanism between Oc1and Oc2L are the same with those between Oc1 and Oc2M; and (2) NMDAR activation results in non-NMDAR activity, resulting in opening and strengthening of intrinsic signal pathways between Oc1 and Oc2. NMDAR-dependent forward and backward propagation might be involved in cortical reorganization of the visual cortex.
Assuntos
Relógios Biológicos/fisiologia , Neurônios/fisiologia , Receptores de Neurotransmissores/fisiologia , Transmissão Sináptica/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Relógios Biológicos/efeitos dos fármacos , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Neurônios/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/fisiologia , Receptores de Neurotransmissores/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Sinapses/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Córtex Visual/anatomia & histologia , Córtex Visual/efeitos dos fármacos , Vias Visuais/anatomia & histologia , Vias Visuais/efeitos dos fármacosRESUMO
The retrosplenial cortex is located at a critical juncture between the visual cortex and hippocampal formation. Functions of the retrosplenial cortex at the local circuit level, however, remain unclear. Herein, we show how signals traveling from the visual cortex behave in local circuits of the retrosplenial cortex, using optical recording methods and application of caffeine to rat brain slices. Electrical signals evoked in the primary visual cortex penetrated into the deep layer of the retrosplenial granular a cortex (RSGa) and propagated further toward postsubiculum and upper layer. Non-N-methyl-D-aspartate (NMDA) receptor-dependent initial traveling signal from the visual cortex triggered NMDA receptor-dependent neural oscillation in the RSGa. Oscillatory signals originated from the local area in the deep layer of the RSGa, and the signal spread back and forth toward the visual cortex and postsubiculum, in addition to spreading toward the upper layer. From the perspective of the RSGa, extrinsic signal inputs from the visual cortex switched on neural oscillators in the RSGa that deliver NMDA receptor-dependent intrinsic signal outputs. Opening and strengthening of non-NMDA receptor-dependent input pathways from the visual cortex required NMDA receptor-dependent oscillatory neural activities. These input and output relationships indicate that the retrosplenial cortex may represent an important relay station between the visual cortex and hippocampal formation.
Assuntos
Relógios Biológicos/fisiologia , Giro do Cíngulo/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Relógios Biológicos/efeitos dos fármacos , Cafeína/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Corantes Fluorescentes , Ácido Glutâmico/metabolismo , Giro do Cíngulo/anatomia & histologia , Giro do Cíngulo/efeitos dos fármacos , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Óptica e Fotônica , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Córtex Visual/anatomia & histologia , Córtex Visual/efeitos dos fármacos , Vias Visuais/anatomia & histologia , Vias Visuais/efeitos dos fármacosRESUMO
Homer1a is implicated in depression in humans and depression-like behavior in mice. To further understand the role of Homer1a in stress-induced emotional changes, we applied very mild stress to Homer1a knockout (H1a KO) mice. The wild-type (WT) and H1a KO mice were restrained for 2h daily for 7 consecutive days at the same time of the day. The restraint was so mild that no changes in anxiety- or depression-like behavior were detected in either type of mice. However, total locomotion in the open field test and forced swimming test was increased by restraint in H1a KO mice only. After behavior, we made brain slices to examine neuronal excitability in cingulate cortex pyramidal cells and synaptic efficiency in hippocampal CA1 synapses. The excitability, assessed on the basis of the frequency of spikes elicited by current injection, was increased by restraint in H1a KO mice. The synaptic efficiency was evaluated by comparing the input-output relationship between the size of fiber volley and the slope of field excitatory postsynaptic potentials, and was shown to be increased by restraint in H1a KO mice only. Thus, predictable subtle stress, which failed to induce behavioral or electrophysiological changes in WT mice, resulted in a minor behavioral change that accompany upregulation of neuronal excitability and synaptic efficiency in H1a KO mice, suggesting that Homer1a may play a critical role in resilience to subtle stress.
Assuntos
Comportamento Animal/fisiologia , Proteínas de Transporte/fisiologia , Estresse Fisiológico/fisiologia , Animais , Ansiedade/etiologia , Região CA1 Hipocampal/fisiologia , Depressão/etiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Proteínas de Arcabouço Homer , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Piramidais/fisiologia , Restrição FísicaRESUMO
We previously showed that activity of the large conductance calcium-activated potassium (Big-K; BK) channels is suppressed in 3xTg Alzheimer disease (AD) model mice. However, its behavioral significance is not known. In the present report, ventricular injection of the BK channel activator isopimaric acid (ISO) was conducted to examine whether BK channel activation ameliorates cognition in 3xTg mice. The novel object recognition (NOR) test revealed that chronic injection of ISO improved non-spatial memory in 3xTg mice. In the Morris water maze, the probe test demonstrated an improved spatial memory after ISO injection. Electrophysiological underpinnings of the ISO effect were then examined in slices obtained from the mice after behavior. At hippocampal CA1 synapses, the basic synaptic transmission was abnormally elevated and long-term potentiation (LTP) was partially suppressed in 3xTg mice. These were both recovered by ISO treatment. We then confirmed suppressed BK channel activity in 3xTg mice by measuring the half-width of evoked action potentials. This was also recovered by ISO treatment. We previously showed that the recovery of BK channel activity accompanies reduction of neuronal excitability in pyramidal cells. Here again, pyramidal cell excitability, as assessed by calculating the frequency of evoked spikes, was elevated in the 3xTg mouse and was normalized by ISO. ELISA experiments demonstrated an ISO-induced reduction of Aß1-42 content in hippocampal tissue in 3xTg mice. The present study thus suggests a potential therapeutic utility of BK channel activators for AD.
Assuntos
Doença de Alzheimer/complicações , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/fisiologia , Ácidos Carboxílicos/uso terapêutico , Charibdotoxina/administração & dosagem , Transtornos Cognitivos/tratamento farmacológico , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Técnicas In Vitro , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurotoxinas/administração & dosagem , Técnicas de Patch-Clamp , Fragmentos de Peptídeos/metabolismo , Fenantrenos/uso terapêutico , Reconhecimento Psicológico/efeitos dos fármacosRESUMO
Transcranial magnetic stimulation (TMS) is fragmentarily reported to be beneficial to Alzheimer's patients. Its underlying mechanism was investigated. TMS was applied at 1, 10 or 15 Hz daily for 4 weeks to young Alzheimer's disease model mice (3xTg), in which intracellular soluble amyloid-ß is notably accumulated. Hippocampal long-term potentiation (LTP) was tested after behavior. TMS ameliorated spatial learning deficits and enhanced LTP in the same frequency-dependent manner. Activity of the large conductance calcium-activated potassium (Big-K; BK) channels was suppressed in 3xTg mice and recovered by TMS frequency-dependently. These suppression and recovery were accompanied by increase and decrease in cortical excitability, respectively. TMS frequency-dependently enhanced the expression of the activity-dependently expressed scaffold protein Homer1a, which turned out to enhance BK channel activity. Isopimaric acid, an activator of the BK channel, magnified LTP. Amyloid-ß lowering was detected after TMS in 3xTg mice. In 3xTg mice with Homer1a knocked out, amyloid-ß lowering was not detected, though the TMS effects on BK channel and LTP remained. We concluded that TMS facilitates BK channels both Homer1a-dependently and -independently, thereby enhancing hippocampal LTP and decreasing cortical excitability. Reduced excitability contributed to amyloid-ß lowering. A cascade of these correlated processes, triggered by TMS, was likely to improve learning in 3xTg mice.
Assuntos
Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/terapia , Hipocampo/fisiopatologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Aprendizagem em Labirinto/fisiologia , Estimulação Magnética Transcraniana , Animais , Ácidos Carboxílicos/farmacologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Proteínas de Arcabouço Homer , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Moduladores de Transporte de Membrana/farmacologia , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Fenantrenos/farmacologia , Técnicas de Cultura de TecidosRESUMO
We previously reported that activity of the large conductance calcium-activated potassium (big-K, BK) channel is suppressed by intracellular Aß in cortical pyramidal cells, and that this suppression was reversed by expression of the scaffold protein Homer1a in 3xTg Alzheimer's disease model mice. Homer1a is known to be expressed by physiological photic stimulation (PS) as well. The possibility thus arises that PS also reverses Aß-induced suppression of BK channels, and thereby improves cognition in 3xTg mice. This possibility was tested here. Chronic application of 6-hour-long PS (frequency, 2 Hz; duty cycle, about 1/10; luminance, 300 lx) daily for 4 weeks improved contextual and tone-dependent fear memory in 3xTg mice and, to a lesser extent, Morris water maze performance as well. Hippocampal long-term potentiation was also enhanced after PS. BK channel activity in cingulate cortex pyramidal cells and lateral amygdalar principal cells, suppressed in 3xTg mice, were facilitated. In parallel, neuronal excitability, elevated in 3xTg mice, was recovered to the control level. Gene expression of BK channel, as well as that of the scaffold protein Homer1a, was found decreased in 3xTg mice and reversed by PS. It is known that Homer1a is an activity-dependently inducible immediate early gene product. Consistently, our previous findings showed that Homer1a induced by electrical stimulation facilitated BK channels. By using Homer1a knockouts, we showed that the present PS-induced BK channel facilitation is mediated by Homer1a expression. We thus propose that PS might be potentially useful as a non-invasive therapeutic measure against Alzheimer's disease.
Assuntos
Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/terapia , Encéfalo/fisiopatologia , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Fototerapia/métodos , Doença de Alzheimer/psicologia , Animais , Percepção Auditiva/fisiologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Medo/fisiologia , Expressão Gênica , Proteínas de Arcabouço Homer , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Potenciação de Longa Duração/fisiologia , Masculino , Camundongos Transgênicos , Neurônios/fisiologia , Técnicas de Cultura de Tecidos , Resultado do TratamentoRESUMO
Effects of some glutamate receptor antagonists on signal propagation elicited by stimulation of association fibers in guinea pig piriform cortex slices were investigated using optical imaging. During simultaneous application of both NMDA and non-NMDA receptor antagonists (D-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively) the postsynaptic activity was largely suppressed, and a weak although distinct late propagation component was found to survive. This latter component was reversibly suppressed by application of low Ca(2+) solution or a group I/II specific metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl-4-carboxyphenylglycine. These results suggest that mGluRs mediate postsynaptic excitation, which would play a crucial role in activating the reverberating positive feedback circuit effectively.
Assuntos
Córtex Cerebral/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/fisiologia , Animais , Córtex Cerebral/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Cobaias , Técnicas In Vitro , Receptores de Glutamato Metabotrópico/antagonistas & inibidoresRESUMO
To examine whether cortical taste neurons use spatial codes for discriminating taste information, we investigated the spatial aspects of optical intrinsic signal (OIS) responses in the gustatory insular cortex (GC) elicited by the administration of two essential tastants, sucrose and NaCl, on the tongue. OIS responses to sucrose appeared in the rostral part of the GC, whereas those to NaCl appeared in the central part of the GC. Local anesthetization of the tongue abolished OIS responses, and the administration of distilled water elicited no OIS response. Thus, taste information elicited by sucrose and NaCl from the peripheral sensory organs is segregated in the GC, suggesting that the information from two essential tastants is assembled as spatial codes in the primary cortical taste area through the process of taste quality perception.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Sacarose/farmacologia , Paladar/efeitos dos fármacos , Paladar/fisiologia , Animais , Córtex Cerebral/fisiologia , Cobaias , Óptica e Fotônica , Gravação em Vídeo/métodosRESUMO
Developmental changes in dynamics of signal propagation between the primary (Oc1) and secondary visual cortex (Oc2) were investigated by using optical recording methods with voltage-sensitive dyes. Propagating oscillatory optical responses were evoked by our previously reported procedure, and were recorded on stimulation to white matter of Oc1 in rat visual cortex slices. In immature slices, evoked signals spread out from the stimulation site by way of deep layers, but were restricted largely to Oc1. In mature slices, however, evoked signals spread upward from the stimulation site at first, and then spread out along layer II/III, finally to penetrate Oc2. More remarkably, after this initial signal was attenuated, oscillatory responses emerged and spread back from Oc2 to Oc1 by way of layer II/III, suggesting that the origin of backpropagating oscillation is located in Oc2. The initial forward component was dependent on both N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and the subsequent backward components were dependent only on NMDA receptors. These results suggest that the extent of corticocoritcal signal propagation within the visual cortex grows wider horizontally during maturation, so that information interchange may become easier between the Oc1 and Oc2.
Assuntos
Envelhecimento/fisiologia , Transdução de Sinais/fisiologia , Córtex Visual/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Cafeína/farmacologia , Cálcio/metabolismo , Estimulação Elétrica , Eletrofisiologia , Potenciais Evocados/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Técnicas In Vitro , Potenciais da Membrana/fisiologia , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Tetrodotoxina/farmacologiaRESUMO
Taste perception depends not only on special taste information processed in the insular cortex, but also on oral somesthetic processing in the parietal cortex. Many insular cortex neurons show multimodal responsiveness. Such multimodality may be enabled by signal exchange between these two cortices. By using the protocol that we have developed, a synchronized population oscillation of synaptic potentials was induced in the parietal cortex by stimulation to the insular cortex in rat neocortex slices. The spatiotemporal pattern of propagation of this oscillation was studied by recording voltage-sensitive optical signals and field potentials. The first wavelet of the oscillation was propagated from the insular stimulation site to the parietal cortex. However, the second and later wavelets propagated back from the parietal cortex to the insular cortex. The oscillation was detected in the insular cortex as well, but was actually generated in the parietal cortex. Thus, the initial peak of optical signal, sent from the insular to parietal cortex, served to generate oscillatory responses in the parietal cortex, which propagated back to the insular cortex wave-by-wave. We propose that this to-and-fro propagation may be an artificially exaggerated demonstration of an intrinsic mechanism relevant to signal exchange between the parietal and insular cortices.
Assuntos
Córtex Cerebral/fisiologia , Sincronização Cortical , Potenciais Somatossensoriais Evocados/fisiologia , Transdução de Sinais/fisiologia , Paladar/fisiologia , Animais , Cafeína/farmacologia , Córtex Cerebral/efeitos dos fármacos , Estimulação Elétrica , Eletrofisiologia , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Corantes Fluorescentes , Boca/fisiologia , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiologia , Técnicas de Cultura de Órgãos , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/fisiologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Paladar/efeitos dos fármacosRESUMO
Synchronized population oscillation of delta to alpha range frequencies was synaptically induced in rat visual cortex neurons, depending on (1) the extent of N-methyl-D-aspartate (NMDA) receptor activation, (2) occurrence of calcium-induced calcium release (CICR), and (3) the age of animals. In adult slices bathed with 0.1 mM Mg(2+), as white matter stimulation continued, solitary synaptic potentials gradually became enlarged and overridden by small wavelets oscillating at alpha range frequencies. The calcium store depeletor thapsigargin prevented appearance of these wavelets. When Mg(2+) block of NMDA receptors was intensified with 0.5 or 2.0 mM Mg(2+), the oscillation failed to be induced, but became inducible by caffeine, which facilitates CICR. NMDA receptor blockade abolished induction of the oscillation even under caffeine application. In immature slices, the induction of oscillation was possible only with 0.1 mM Mg(2+) and bath-applied caffeine, but failed with 0.5 mM Mg(2+) or without caffeine. The oscillation induced in immature tissue was smaller in amplitude and frequency (delta-theta; range) than in adult tissue (alpha range). Immature tissue thus requires more restricted conditions for inducing the oscillation. We propose that NMDA and ryanodine receptors become coupled during maturation to enhance synaptically induced intracellular calcium releases, thereby facilitating induction of the oscillation at later stages.
Assuntos
Neocórtex/crescimento & desenvolvimento , Neocórtex/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Fatores Etários , Animais , Cafeína/farmacologia , Cálcio/metabolismo , Inibidores Enzimáticos/farmacologia , Magnésio/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Periodicidade , Inibidores de Fosfodiesterase/farmacologia , Ratos , Ratos Wistar , Tapsigargina/farmacologia , Córtex Visual/crescimento & desenvolvimento , Córtex Visual/metabolismoRESUMO
We investigated postnatal development of a functional connectivity from the gustatory insular cortex to the parietal cortex, which is known to contain many more neurons responding to oral somesthetic stimulation than the insular cortex, in slices obtained from 9-35-day-old rats. Field potentials were evoked by stimulation to the insular cortex. In the mature cortex, insular stimulation elicited a solitary field potential in both the insular and parietal cortices and, as the simulation continued, the initial solitary potential came to be followed by a population oscillation of field potential in the parietal cortex, but not in the insular cortex. In the immature cortex, by contrast, insular stimulation failed to evoke both the initial solitary potential and the subsequent population oscillation in the parietal cortex. In the mature cortex, application of neither thapsigargin nor AP5 prevented elicitation of the initial solitary potential in the parietal cortex, but either of them abolished the parietal oscillation. In immature cortex bathed with low Mg(2+) medium, insular stimulation elicited both the initial solitary potential and the subsequent parietal oscillation, which were both prevented by thapsigargin or AP5. Theses results suggest that the insular and parietal cortices are anatomically connected but functionally unlinked at an early postnatal stage, and that a functional linkage, dependent both on NMDA and ryanodine receptors, is formed during the first postnatal month.
Assuntos
Sincronização Cortical , Vias Neurais/fisiologia , Lobo Parietal/crescimento & desenvolvimento , Lobo Parietal/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Fatores Etários , Animais , Animais Recém-Nascidos , Relógios Biológicos/fisiologia , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Sincronização Cortical/efeitos dos fármacos , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Magnésio/metabolismo , Vias Neurais/anatomia & histologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Tapsigargina/farmacologiaRESUMO
By using the procedure that we developed for inducing population oscillation, it was previously demonstrated that insular cortex stimulation can evoke insulo-parietal field potential propagation and synchronized population oscillation in the parietal cortex in slices obtained from mature rats (27-35 days old). By using the same procedure, we have now studied the reciprocal parieto-insular projection. Parietal cortex stimulation elicited synchronized population oscillation in the parietal--but not insular--cortex in mature tissues. In the insular cortex, the initial wavelet of the oscillation generated by parietal cortex stimulation propagated, but the entire oscillation did not. A prior induction--but not simultaneous occurrence--of oscillation in the parietal cortex sufficed to have this initial wavelet propagate. In immature tissue (9-10 days old), both the parietal cortex oscillation and the parieto-insular propagation were induced only with low [Mg2+]o. This age dependence is exactly the same as we previously observed for the reciprocal insulo-parietal propagation. Given that the parietal cortex receives somatosensory inputs from the oral cavity and the insular cortex receives primarily chemosensory inputs from the same source, the age-dependent changes in the availability of bidirectional signal traffic between these cortices might contribute to the development of multimodal responsiveness of taste neurons.