Selective Coupling between Theta Phase and Neocortical Fast Gamma Oscillations during REM-Sleep in Mice

TORT, A. B. L. ; SCHEFFER-TEIXEIRA, R ; Souza, B.C. ; DRAGUHN, A. ; BRANKACK, J. . Theta-associated high-frequency oscillations (110-160 Hz) in the hippocampus and neocortex. Progress in Neurobiology , v. 100, p. 1-14, 2013.

Caracterização dos acoplamentos fase-amplitude na região CA1 do hopocampo

Brain oscillation are not completely independent, but able to interact with each other through cross-frequency coupling (CFC) in at least four different ways: power-to-power, phase-to-phase, phase-to-frequency and phase-to-power. Recent evidence suggests that not only the rhythms per se, but also their interactions are involved in the execution of cognitive tasks, mainly those requiring selective attention, information flow and memory consolidation. It was recently proposed that fast gamma oscillations (60 150 Hz) convey spatial information from the medial entorhinal cortex to the CA1 region of the hippocampus by means of theta (4-12 Hz) phase coupling. Despite these findings, however, little is known about general characteristics of CFCs in several brain regions. In this work we recorded local field potentials using multielectrode arrays aimed at the CA1 region of the dorsal hippocampus for chronic recording. Cross-frequency coupling was evaluated by using comodulogram analysis, a CFC tool recently developted (Tort et al. 2008, Tort et al. 2010). All data analyses were performed using MATLAB (MathWorks Inc). Here we describe two functionally distinct oscillations within the fast gamma frequency range, both coupled to the theta rhythm during active exploration and REM sleep: an oscillation with peak activity at ~80 Hz, and a faster oscillation centered at ~140 Hz. The two 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 ~80 Hz oscillation originates from entorhinal cortex inputs to deeper CA1 layers, while the ~140 Hz oscillation reflects CA1 activity in superficial layers. We further show that the ~140 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

The influence of visual inter-hemispheric connections on spiking, assembly and LFP activities, and their phase relationship during figure-ground stimulation

Desde os descobrimentos pioneiros de Hubel e Wiesel acumulou-se uma vasta literatura descrevendo as respostas neuronais do córtex visual primário (V1) a diferentes estímulos visuais. Estes estímulos consistem principalmente em barras em movimento, pontos ou grades, que são úteis para explorar as respostas dentro do campo receptivo clássico (CRF do inglês classical receptive field) a características básicas dos estímulos visuais como a orientação, direção de movimento, contraste, entre outras. Entretanto, nas últimas duas décadas, tornou-se cada vez mais evidente que a atividade de neurônios em V1 pode ser modulada por estímulos fora do CRF. Desta forma, áreas visuais primárias poderiam estar envolvidas em funções visuais mais complexas como, por exemplo, a separação de um objeto ou figura do seu fundo (segregação figura-fundo) e assume-se que as conexões intrínsecas de longo alcance em V1, assim como as conexões de áreas visuais superiores, estão ativamente envolvidas neste processo. Sua possível função foi inferida a partir da análise das variações das respostas induzidas por um estímulo localizado fora do CRF de neurônios individuais. Mesmo sendo muito provável que estas conexões tenham também um impacto tanto na atividade conjunta de neurônios envolvidos no processamento da figura quanto no potencial de campo, estas questões permanecem pouco estudadas. Visando examinar a modulação do contexto visual nessas atividades, coletamos potenciais de ação e potenciais de campo em paralelo de até 48 eletrodos implantados na área visual primária de gatos anestesiados. Estimulamos com grades compostas e cenas naturais, focando-nos na atividade de neurônios cujo CRF estava situado na figura. Da mesma forma, visando examinar a influência das conexões laterais, o sinal proveniente da área visual isotópica e contralateral foi removido através da desativação reversível por resfriamento. Fizemos isso devido a: i) as conexões laterais intrínsecas não podem ser facilmente manipuladas sem afetar diretamente os sinais que estão sendo medidos, ii) as conexões inter-hemisféricas compartilham as principais características anatômicas com a rede lateral intrínseca e podem ser vistas como uma continuação funcional das mesmas entre os dois hemisférios e iii) o resfriamento desativa as conexões de forma causal e reversível, silenciando temporariamente seu sinal, permitindo conclusões diretas a respeito da sua contribuição. Nossos resultados demonstram que o mecanismo de segmentação figurafundo se reflete nas taxas de disparo de neurônios individuais, assim como na potência do potencial de campo e na relação entre sua fase e os padrões de disparo produzidos pela população. Além disso, as conexões laterais inter-hemisféricas modulam estas variáveis dependendo da estimulação feita fora do CRF. Observamos também uma influência deste circuito lateral na coerência entre potenciais de campo entre eletrodos distantes. Em conclusão, nossos resultados dão suporte à ideia de um mecanismo complexo de segmentação figura-fundo atuando desde as áreas visuais primárias em diferentes escalas de frequência. Esse mecanismo parece envolver grupos de neurônios ativos sincronicamente e dependentes da fase do potencial de campo. Nossos resultados também são compatíveis com a hipótese que conexões laterais de longo alcance também fazem parte deste mecanismo

Caracterização de células de lugar no hipocampo e de suas relações com oscilações do potencial de campo local

The main inputs to the hippocampus arise from the entorhinal cortex (EC) and form a loop involving the dentate gyrus, CA3 and CA1 hippocampal subfields and then back to EC. Since the discovery that the hippocampus is involved in memory formation in the 50's, this region and its circuitry have been extensively studied. Beyond memory, the hippocampus has also been found to play an important role in spatial navigation. In rats and mice, place cells show a close relation between firing rate and the animal position in a restricted area of the environment, the so-called place field. The firing of place cells peaks at the center of the place field and decreases when the animal moves away from it, suggesting the existence of a rate code for space. Nevertheless, many have described the emergence of hippocampal network oscillations of multiple frequencies depending on behavioral state, which are believed to be important for temporal coding. In particular, theta oscillations (5-12 Hz) exhibit a spatio-temporal relation with place cells known as phase precession, in which place cells consistently change the theta phase of spiking as the animal traverses the place field. Moreover, current theories state that CA1, the main output stream of the hippocampus, would interplay inputs from EC and CA3 through network oscillations of different frequencies, namely high gamma (60-100 Hz; HG) and low gamma (30-50 Hz; LG), respectively, which tend to be nested in different phases of the theta cycle. In the present dissertation we use a freely available online dataset to make extensive computational analyses aimed at reproducing classical and recent results about the activity of place cells in the hippocampus of freely moving rats. In particular, we revisit the debate of whether phase precession is due to changes in firing frequency or space alone, and conclude that the phenomenon cannot be explained by either factor independently but by their joint influence. We also perform novel analyses investigating further characteristics of place cells in relation to network oscillations. We show that the strength of theta modulation of spikes only marginally affects the spatial information content of place cells, while the mean spiking theta phase has no influence on spatial information. Further analyses reveal that place cells are also modulated by theta when they fire outside the place field. Moreover, we find that the firing of place cells within the theta cycle is modulated by HG and LG amplitude in both CA1 and EC, matching cross-frequency coupling results found at the local field potential level. Additionally, the phase-amplitude coupling in CA1 associated with spikes inside the place field is characterized by amplitude modulation in the 40-80 Hz range. We conclude that place cell firing is embedded in large network states reflected in local field potential oscillations and suggest that their activity might be seen as a dynamic state rather than a fixed property of the cell.

Selective Coupling between Theta Phase and Neocortical Fast Gamma Oscillations during REM-Sleep in Mice

TORT, A. B. L. ; SCHEFFER-TEIXEIRA, R ; Souza, B.C. ; DRAGUHN, A. ; BRANKACK, J. . Theta-associated high-frequency oscillations (110-160 Hz) in the hippocampus and neocortex. Progress in Neurobiology , v. 100, p. 1-14, 2013.