Theta-Frequency Bursting and Resonance in Cerebellar Granule Cells: Experimental Evidence and Modeling of a Slow K⁺-Dependent Mechanism

Abstract

Neurons process information in a highly nonlinear manner, generating oscillations, bursting, and resonance, enhancing responsiveness at preferential frequencies. It has been proposed that slow repolarizing currents could be responsible for both oscillation/burst termination and for high-pass filtering that causes resonance (Hutcheon and Yarom, 2000). However, different mechanisms, including electrotonic effects (Mainen and Sejinowski, 1996), the expression of resurgent currents (Raman and Bean, 1997), and network feedback, may also be important. In this study we report theta-frequency (3-12 Hz) bursting and resonance in rat cerebellar granule cells and show that these neurons express a previously unidentified slow repolarizing K ϩ current (I K-slow ). Our experimental and modeling results indicate that I K-slow was necessary for both bursting and resonance. A persistent (and potentially a resurgent) Na ϩ current exerted complex amplifying actions on bursting and resonance, whereas electrotonic effects were excluded by the compact structure of the granule cell. Theta-frequency bursting and resonance in granule cells may play an important role in determining synchronization, rhythmicity, and learning in the cerebellum.

Postsynaptic modulation of electrical EPSP size investigated using a compartmental model

“…We assigned a non-inactivating potassium current, I KV to the soma and tuned the activation rates and maximum conductance to …t the data. This type of current has been previously identi…ed in cerebellar granule cells (D'Angelo et al , 2001). The input resistance was measured directly and the capacitance could be determined from the resistance and the time constant.…”

“…This suggests that there exists a spike termination mechanism, which we hypothesize is a slow activating, non-inactivating potassium current I KM . This current has been shown to be present in cerebellar granule cells (D'Angelo et al , 2001), where it contributes to the intrinsic bursting and resonance. In the granular cells, this current could contribute to the termination of the burst of spikes, thus playing a central role in the encoding of a¤erent latency into a spike burst.…”

Presumed mechanisms of a long-term increase in the intrinsic excitability of cerebellar granule cells: A model study

“…In our study we used the model of rat cerebellar GrC electrical activity developed by D'Angelo et al [16] on the basis of experimentally measured conductances described by means of the Hodgkin−Huxley formalism. The description of this model and all its parameters are given in the Methods section and in Table 1 of the above-cited work.…”

Enabling a Freely Accessible Open Source Remotely Controlled Robotic Articulator with a Neuro-Inspired Control Algorithm

“…We modelled inputs as in sparse coded patterns of granular layer. As in a rat cerebellum, each granule cell is known to receive around 3-5 mossy fibres [30]. Sparse coded granule cell activities are integrated and the spike information is passed to the Purkinje cell.…”