Effekt von frequenz-modulierter artifizieller synaptischer Aktivitaet auf das elektrophysiologische Verhalten von CA1 Pyramiden Zellen.
Zusammenfassung der Projektergebnisse
Rhythmic activity in a wide range of frequencies has been observed in the central nervous system during different behavioral states, and the frequency-response characteristics of individual neurons are believed to be critical for network oscillations. In the hippocampal formation, three prominent types of oscillatory activity have been described: the theta (4-12 Hz), gamma (30-80 Hz), and sharp-wave/ripple oscillations (100-200 Hz). The theta oscillation, which is observed during explorative behavior and REM sleep, is of particular prominence. However, the network and cellular mechanisms involved in the generation and maintenance of the theta oscillations are still unclear. Recent in vivo studies suggest that neurons experience periods of high membrane conductance and that action potentials are often driven by noisy membrane potential fluctuations in the living animal. To investigate how the firing rate of CA1 pyramidal neurons encodes time-varying stimuli, dynamic-clamp experiments in brain slice preparations have been conducted. Dynamic-clamp technology was used to replicate in vivo conditions in an in vitro preparation by introducing membrane voltage fluctuations and changes in background conductance to the recorded neurons. Neurons were driven by noisy stimuli that included a sinusoidal component ranging from 0.1 to 500 Hz. Action potential phase locking was determined with respect to background conductance, average firing rate, and frequency of the sinusoidal component. It was found that background conductance and firing rate qualitatively change the phase locking profiles of CA1 pyramidal neurons vs. frequency. Increases in background conductance allowed phase locking to frequencies well beyond what would have been predicted from changes in the membrane time constant, indicating a distinction between sub- and suprathreshold cutoff frequencies. In addition to the cutoff frequency, spike frequency adaptation, and an intrinsic frequency preference of the spike-generation mechanism were found to be involved in setting the phase locking profiles of CA1 pyramidal neurons. The sensitivity of the three mechanisms to average firing rate and background conductance resulted in a diversity of low-pass and band-pass responses. Increasing background conductance at low firing rates, changed the locking profile from low-pass to band-pass, peaking within the theta range. Increasing firing rate resulted in band-pass profiles, peaking in the theta band under low-conductance, and in the betagamma band under high conductance. From a functional perspective, the overall network state likely translates into the drive, magnitude of voltage fluctuations and total synaptic conductance a neuron is exposed to. We show the dependence of action potential phase locking on these parameters. In this context, our findings imply that the ability of CA1 pyramidal neurons to participate in a network rhythm of a given frequency depends on the overall network state. Thus, CA1 pyramidal neurons should not be thought of as invariable network elements, but rather as active units, able to modify their behavior according to global changes in hippocampal activity.
Projektbezogene Publikationen (Auswahl)
- (2012) Spike Phase Locking in CA1 Pyramidal Neurons depends on Background Conductance and Firing Rate. Annual meeting of the Society for Neuroscience in New Orleans from October 13-17, 2012, in New Orleans
Tilman Broicher, Paola Malerba, Alan Dorval, Alla Borisyuk, Fernando Fernandez, and John White
