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Identifier

000376207

Title

Characterization of the mechanisms underlying the emergence of up and down states in a prefrontal cortex model microcircuit

Alternative Title

Χαρακτηρισμός των μηχανισμών που ευθύνονται για την εμφάνιση των up and down states σε ένα μοντέλο μικροκυκλώματος του προμετωπιαίου φλοιού

Author

Krioneriti, Daphne

Author

Κρυονερίτη, Δάφνη

Thesis advisor

Ποιράζη

Abstract

Up and Down states are oscillations between periods of prolonged activity (Up state) and quiescence (Down state) and are recorded both in vivo and in vitro in layer V prefrontal cortex (PFC) pyramidal neurons. Biophysical mechanisms that have been proposed to underlie this phenomenon include the balance of excitation and inhibition within local PFC networks along with certain intrinsic membrane mechanisms such as the afterdepolarization. Using a biophysical compartmental network model of PFC layer V pyramidal neurons that incorporates anatomical data, we investigated the role of synaptic input, intrinsic currents and local interconnectivity in the following features of Up and Down states: (a) the emergence of Up and Down states, (b) the duration of Up states, (c) the frequency of Up states and (d) the firing frequency during the Up state. We found that Up and Down states could emerge in our model microcircuit, provided the existence of background synaptic activity. Among the various conditions we examined, statistically significant results were obtained when: ‐ Increasing the firing frequency of the background synaptic input or the number of activated background synapses. ‐ Blocking the NMDA current, while compensating for the reduced excitability by enhancing the AMPA current (no emergence of Up and Down states). ‐ Increasing the iNMDA‐to‐iAMPA ratio. ‐ Activating the dADP mechanism at a physiological value (4mV). Our results indicate that the generation of Up states in PFC is likely to involve not only a balance of excitation/inhibition provided within a microcircuit but also single‐neuron dynamics shaped by intrinsic mechanisms. Interestingly, the duration of the Up state was significantly altered in three of the conditions tested, namely, increased frequency of the background excitation, the enhancement of the NMDA current and the activation of the dADP mechanism. These findings suggest that the transition to more prolonged depolarizations is carefully controlled by the same mechanisms that have been associated with persistent firing during working memory tasks.

Language

Greek

Subject

Prefrontal cortex

Up and down states

Working memory

Μνήμη εργασίας

Πρωμετωπιαίος φλοιός

Issue date

2011-12-15

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses