RESUMO
Recent reports converge to the idea that high-frequency oscillations in local field potentials (LFPs) represent multiunit activity. In particular, the amplitude of LFP activity above 100 Hz-commonly referred to as "high-gamma" or "epsilon" band-was found to correlate with firing rate. However, other studies suggest the existence of true LFP oscillations at this frequency range that are different from the well established ripple oscillations. Using multisite recordings of the hippocampus of freely moving rats, we show here that high-frequency LFP oscillations can represent either the spectral leakage of spiking activity or a genuine rhythm, depending on recording location. Both spike-leaked, spurious activity and true fast oscillations couple to theta phase; however, the two phenomena can be clearly distinguished by other key features, such as preferred coupling phase and spectral signatures. Our results argue against the idea that all high-frequency LFP activity stems from spike contamination and suggest avoiding defining brain rhythms solely based on frequency range.
Assuntos
Potenciais de Ação/fisiologia , Região CA1 Hipocampal/fisiologia , Animais , Eletrofisiologia , RatosRESUMO
It was recently proposed that fast gamma oscillations (60-150 Hz) convey spatial information from the medial entorhinal cortex (EC) to the CA1 region of the hippocampus. However, here we describe 2 functionally distinct oscillations within this frequency range, both coupled to the theta rhythm during active exploration and rapid eye movement sleep: an oscillation with peak activity at â¼80 Hz and a faster oscillation centered at â¼140 Hz. The 2 oscillations are differentially modulated by the phase of theta depending on the CA1 layer; theta-80 Hz coupling is strongest at stratum lacunosum-moleculare, while theta-140 Hz coupling is strongest at stratum oriens-alveus. This laminar profile suggests that the â¼80 Hz oscillation originates from EC inputs to deeper CA1 layers, while the â¼140 Hz oscillation reflects CA1 activity in superficial layers. We further show that the â¼140 Hz oscillation differs from sharp wave-associated ripple oscillations in several key characteristics. Our results demonstrate the existence of novel theta-associated high-frequency oscillations and suggest a redefinition of fast gamma oscillations.
Assuntos
Relógios Biológicos/fisiologia , Região CA1 Hipocampal/fisiologia , Rede Nervosa/fisiologia , Ritmo Teta/fisiologia , Animais , Masculino , Ratos , Ratos Long-Evans , Ratos WistarRESUMO
The modulation of memory processes is one of the several functions of the endocannabinoid system (ECS) in the brain, with CB1 receptors highly expressed in areas such as the dorsal hippocampus. Experimental evidence suggested an important role of the ECS in aversively motivated memories. Similarly, glucocorticoids released in response to stress exposure also modulates memory formation, and both stress and dexamethasone activate the ECS. Here, we investigate the interaction between the ECS and glucocorticoids in the hippocampus in the modulation of fear memory consolidation. Two protocols with different shock intensities were used in order to control the level of aversiveness. Local infusion of AM251 into the hippocampus immediately after training was amnestic in the strong, but not in the weak protocol. Moreover, AM251 was amnestic in animals stressed 0, but not 30-min prior to the weak protocol, reverting the stress-induced facilitatory effect. Finally, intrahippocampal AM251 infusion reduced memory in animals that received dexamethasone immediately, but not 30 min before training. These results are (1) consistent with the view that the dorsal hippocampus ECS is activated on demand, in a rapid and short-lived fashion in order to modulate the consolidation of an aversive memory, and (2) show that this recruitment seems to be mediated by glucocorticoids, either in the hippocampus or in other brain regions functionally associated with the hippocampus.
Assuntos
Moduladores de Receptores de Canabinoides/metabolismo , Endocanabinoides , Medo , Hipocampo/metabolismo , Memória/fisiologia , Estresse Psicológico/patologia , Estresse Psicológico/fisiopatologia , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hipocampo/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Masculino , Memória/efeitos dos fármacos , Mifepristona/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80â¯Hz oscillations, which were efficaciously suppressed by all 5-HT1A agonists and reappeared upon co-administration of the antagonist, WAY100635. At the same time, the peak-frequency of fast 130â¯Hz gamma oscillations and their cross-frequency coupling to low-frequency delta oscillations were modified to a different extent by each of the 5-HT1A agonists. These findings suggest that the common antidyskinetic effects of these drugs may be chiefly attributable to a reversal of the brain state characterized by 80â¯Hz gamma oscillations, whereas the differential effects on fast gamma oscillations may reflect differences in pharmacological properties that might be of potential relevance for non-motor symptoms.
Assuntos
Gânglios da Base/fisiologia , Ondas Encefálicas/efeitos dos fármacos , Córtex Cerebral/fisiologia , Discinesias/tratamento farmacológico , Potenciais Evocados/fisiologia , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Tálamo/fisiologia , Animais , Gânglios da Base/efeitos dos fármacos , Ondas Encefálicas/fisiologia , Córtex Cerebral/efeitos dos fármacos , Modelos Animais de Doenças , Discinesias/etiologia , Estimulação Elétrica/efeitos adversos , Feminino , Levodopa/efeitos adversos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/tratamento farmacológico , Piperazinas/uso terapêutico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptor 5-HT1A de Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Antagonistas da Serotonina/uso terapêutico , Tálamo/efeitos dos fármacosRESUMO
Phase-amplitude coupling analysis shows that theta phase modulates oscillatory activity not only within the traditional gamma band (30-100 Hz) but also at faster frequencies, called high-frequency oscillations (HFOs; 120-160 Hz). To date, however, theta-associated HFOs have been reported by only a small number of laboratories. Here we characterized coupling patterns during active waking (aWk) and rapid eye movement (REM) sleep in local field potentials (LFPs) from the parietal cortex and hippocampus of rats, focusing on how theta-associated HFOs can be detected. We found that electrode geometry and impedance only mildly influence HFO detection, whereas recording location and behavioral state are main factors. HFOs were most prominent in parietal cortex and during REM sleep, although they could also be detected in stratum oriens-alveus and during aWK. The underreporting of HFOs may thus be a result of higher prevalence of recordings from the pyramidal cell layer. However, at this layer, spike-leaked HFOs (SLHFOs) dominate, which represent spike contamination of the LFP and not genuine oscillations. In contrast to HFOs, high-gamma (HG; 60-100 Hz) coupled to theta below the pyramidal cell layer; theta-HG coupling increased during REM sleep. Theta also weakly modulated low-gamma (LG; 30-60 Hz) amplitude, mainly in the parietal cortex; theta-LG coupling did not vary between aWK and REM sleep. HG and HFOs were maximal near the theta peak, parietal LG at the ascending phase, hippocampal LG at the descending phase, and SLHFOs at the trough. Our results unveil four types of fast LFP activity coupled to theta and outline how to detect theta-associated HFOs.
Assuntos
Ondas Encefálicas/fisiologia , Eletrodos Implantados , Hipocampo/fisiologia , Lobo Parietal/fisiologia , Animais , Impedância Elétrica , Masculino , Ratos Wistar , Processamento de Sinais Assistido por Computador , Sono REM/fisiologia , Vigília/fisiologiaRESUMO
Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC.
Assuntos
Ritmo Delta/efeitos dos fármacos , Dopamina/farmacologia , Ritmo Gama/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Vigília , 2,2'-Dipiridil/análogos & derivados , 2,2'-Dipiridil/farmacologia , Animais , Ritmo Delta/fisiologia , Dopamina/metabolismo , Eletroencefalografia , Ritmo Gama/fisiologia , Masculino , Compostos Organometálicos/farmacologia , Estimulação Luminosa/métodos , Ratos , Ratos Wistar , Sono REM/efeitos dos fármacos , Sono REM/fisiologia , Análise Espectral , Fatores de Tempo , Raios UltravioletaRESUMO
Phase-amplitude coupling between theta and multiple gamma sub-bands is a hallmark of hippocampal activity and believed to take part in information routing. More recently, theta and gamma oscillations were also reported to exhibit phase-phase coupling, or n:m phase-locking, suggesting an important mechanism of neuronal coding that has long received theoretical support. However, by analyzing simulated and actual LFPs, here we question the existence of theta-gamma phase-phase coupling in the rat hippocampus. We show that the quasi-linear phase shifts introduced by filtering lead to spurious coupling levels in both white noise and hippocampal LFPs, which highly depend on epoch length, and that significant coupling may be falsely detected when employing improper surrogate methods. We also show that waveform asymmetry and frequency harmonics may generate artifactual n:m phase-locking. Studies investigating phase-phase coupling should rely on appropriate statistical controls and be aware of confounding factors; otherwise, they could easily fall into analysis pitfalls.
Assuntos
Ritmo Gama , Hipocampo/fisiologia , Neurônios/fisiologia , Ritmo Teta , Animais , Eletrofisiologia/métodos , Modelos Neurológicos , RatosRESUMO
We review recent evidence for a novel type of fast cortical oscillatory activity that occurs circumscribed between 110 and 160Hz, which we refer to as high-frequency oscillations (HFOs). HFOs characteristically occur modulated by theta phase in the hippocampus and neocortex. HFOs can co-occur with gamma oscillations nested in the same theta cycle, in which case they typically peak at different theta phases. Despite the overlapping frequency ranges, HFOs differ from hippocampal ripple oscillations in some key characteristics, including amplitude, region of occurrence, associated behavioral state, and activity time-course (sustained vs intermittent). Recent in vitro evidence suggests that HFOs depend on fast GABAergic transmission and may also depend on axonal gap junctions. The functional role of HFOs is currently unclear. Both hippocampal and neocortical theta-HFO coupling increase during REM sleep, suggesting a role for HFOs in memory processing.
Assuntos
Relógios Biológicos/fisiologia , Hipocampo/fisiologia , Neocórtex/fisiologia , Animais , Humanos , Memória/fisiologia , Sono REM/fisiologia , Análise EspectralRESUMO
Recent studies show that higher order oscillatory interactions such as cross-frequency coupling are important for brain functions that are impaired in schizophrenia, including perception, attention and memory. Here we investigated the dynamics of oscillatory coupling in the hippocampus of awake rats upon NMDA receptor blockade by ketamine, a pharmacological model of schizophrenia. Ketamine (25, 50 and 75 mg/kg i.p.) increased gamma and high-frequency oscillations (HFO) in all depths of the CA1-dentate axis, while theta power changes depended on anatomical location and were independent of a transient increase of delta oscillations. Phase coherence of gamma and HFO increased across hippocampal layers. Phase-amplitude coupling between theta and fast oscillations was markedly altered in a dose-dependent manner: ketamine increased hippocampal theta-HFO coupling at all doses, while theta-gamma coupling increased at the lowest dose and was disrupted at the highest dose. Our results demonstrate that ketamine alters network interactions that underlie cognitively relevant theta-gamma coupling.