Hyperpolarization-activated Persistent Activity

Model of hyperpolarization-activated persistent activity
In collaboration with Mavi Sanchez-Vives (University Miguel Hernandez of Alicante, Spain), we have recently modeled a form of persistent activity activated by hyperpolarization (HAGPA) [1]. This form was identified experimentally in rat prefrontal cortex neurons, and was shown to be dependent of the h-type current [1]. To model this phenomenon, our hypothesis was that Ih may be regulated by intracellular calcium, which is itself produced in an activity-dependent fashion. We used the same model as in our previous work on the thalamic Ih [2,3]. By including a high-threshold calcium current, the model reproduced experimental observations, including the HAGPA and its properties as recorded in prefrontal cortex. The model was also used to infer the computational consequences of HAGPA. This form of neuronal memory not only allows the transformation of inhibition into an increase of firing rate, but also endows neurons with a mechanism to compute the properties of successive inputs into persistent activity, thus solving a difficult computational problem (see details in [1]).

[1] Winograd, M., Destexhe, A. and Sanchez-Vives, M.V. Hyperpolarization-activated graded persistent activity in the prefrontal cortex. Proc. Natl. Acad. Sci. USA 105: 7298-7303, 2008 (see abstract) [2] Destexhe, A., Babloyantz, A. and Sejnowski, T.J. Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons. Biophys. J. 65: 1538-1552, 1993 (see abstract) [3] Destexhe, A., Bal, T., McCormick, D.A. and Sejnowski, T.J. Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices. J. Neurophysiol. 76: 2049-2070, 1996 (see abstract)

Alain Destexhe