A defined heteromeric K(V)1 channel stabilizes the intrinsic pacemaking and regulates the output of deep cerebellar nuclear neurons to thalamic targets
Abstract
Key points center dot The result of cerebellar integration is encoded in the output of deep cerebellar nuclear (DCN) neurons in the form of dynamic changes in spontaneous firing rate and pattern. center dot The soma of these neurons has been demonstrated to be enriched with potassium channels (KV1) produced by mandatory multi-merization of KV1.1, 1.2 and KV2 subunits. center dot The outward K+ current (IKV1) mediated by these channels is proven to be a critical stabilizer for both the rate and temporal precision of self-sustained firing of DCN neurons. center dot Activated from low-threshold, IKV1 provides an effective counter-balance to depolarizing inputs, attenuates the back-propagating action potentials, favouring dominance of clock-like somatic pace-making of these cells an important condition for accurate encoding of time variant inputs. center dot The relevance of these observations to physiology and integrative brain mechanisms is shown through a multi-compartmental neuronal model as well as retro-axonal tracing of neurons projecting to thalamic relay nuclei. Abstract The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons.
Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi-merization of KV1.1, 1.2 and KV2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self-sustained firing of these neurons.
Placed strategically, IKV1 provides a powerful counter-balance to prolonged depolarizing inputs, attenuates the rebound excitation, and dampens the membrane potential bi-stability. Somatic location with low activation threshold render IKV1 instrumental in voltage-dependent de-coupling of the axon initial segment from the cell body of projection neurons, impeding invasion of back-propagating action potentials into the somato-dendritic compartment.
The latter is also demonstrated to secure the dominance of clock-like somatic pacemaking in driving the regenerative firing activity of these neurons, to encode time variant inputs with high fidelity. Through the use of multi-compartmental modelling and retro-axonal labelling, the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established.