CNS*2020 Online

Please join my poster presentation via Zoom on:
https://oist.zoom.us/j/97620440229?pwd=SUpuQ2VyZHNMM1huVkNGRk1ic2pPUT09



Gabriela Capo Rangel, Erik De Schutter

Although the effects of inhibition on Purkinje cells have first been first observed over five decades ago and have since then been intensively studied, the manner in which the cerebellar output is regulated by both inhibitory and excitatory cells has yet to be fully understood. Purkinje cells represent the sole output of the cerebellar cortex and are known to fire simple spikes as a result of the integrated excitatory and inhibitory synaptic input originating from parallel fibers and the interneurons in the molecular layer. When studied in vivo, both Purkinje cells and interneurons exhibit a highly irregular pattern in the firing of action potentials. The mechanisms underlying the complex interaction between the intrinsec properties of the membrane and the pattern of synaptic inputs that generate the cerebellar output have not yet been completely understood. Recent literature has underlined the importance of the inhibitory interneurons (stellate and basket cells) in shaping the simple spikes of Purkinje cells. Moreover, when inhibitory interneurons are eliminated and only asynchronous excitation is taken into account, numerous computational [1] and experimental work have reported unrealistic behavior such as very little variability between the spiking intervals, as well as very small minimum firing frequencies. The modeling approach we propose here focuses on analyzing the effects that combined inhibition and excitation have on the shape of action potential, on the firing frequency and on the time intervals in between the simple spikes. The starting point of our work was a very detailed Purkinje cell model proposed by Zang et al in [2]. Instead of varying somatic holding currents as in previous work, in here, the dendritic voltage states are determined by the balance between the frequency of inhibitory cells and the frequency of parallel fibers. Our preliminary results indicate that inhibition presents both subtractive and divisive behavior, depending on stellate cells frequency. We discuss in detail the different shapes of firing we obtained. In particular, our results capture not only simple spikes but also a trimodal firing pattern, previously observed experimentally in [3]. This trimodal firing pattern is a characteristic of mature Purkinje cells and is given by a mixture of three different phases: tonic firing, bursting and silent mode. We mapped the regions in which simple spiking occur and the regions in which simple spikes appear and we further investigate the role of the SK2 channels in eliminating or prolonging the trimodal pattern.

Bibliography:

[1]. De Schutter E, Bower JM, ” An Active Membrane Model of the Cerebellar Purkinje Cell II. Simulation of Synaptic Responses”, Journal of Neurophysiology (1994), 71(1), 401-419.

[2]. Zang Y, Dieudonne S, De Schutter E, ” Voltage- and Branch-Specific Climbing Fiber Responses in Purkinje Cells”, Cell Reports (2018) 24, 1536-1549.

[3]. Womack MD, Khodakhah K, ”Somatic and Dendritic Small-Conductance Calcium- Activated Potassium Channels Regulate the Output of Cerebellar Purkinje Neurons”, The Journal of Neuroscience (2003), 23(7), 2600- 2607.