Human Purkinje cells outperform mouse Purkinje cells in dendritic complexity and computational capacity.

Purkinje cells in the cerebellum are among the largest neurons in the brain and have been extensively investigated in rodents. However, their morphological and physiological properties remain poorly understood in humans. In this study, we utilized high-resolution morphological reconstructions and unique electrophysiological recordings of human Purkinje cells ex vivo to generate computational models and estimate computational capacity.

Stellate cell computational modeling predicts signal filtering in the molecular layer circuit of cerebellum.

The functional properties of cerebellar stellate cells and the way they regulate molecular layer activity are still unclear. We have measured stellate cells electroresponsiveness and their activation by parallel fiber bursts. Stellate cells showed intrinsic pacemaking, along with characteristic responses to depolarization and hyperpolarization, and showed a marked short-term facilitation during repetitive parallel fiber transmission.

Developmental expression of Kv potassium channels at the axon initial segment of cultured hippocampal neurons.

Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation.

GSK3 and β-catenin determines functional expression of sodium channels at the axon initial segment.

Neuronal action potentials are generated through voltage-gated sodium channels, which are tethered by ankyrinG at the membrane of the axon initial segment (AIS). Despite the importance of the AIS in the control of neuronal excitability, the cellular and molecular mechanisms regulating sodium channel expression at the AIS remain elusive. Our results show that GSK3α/β and β-catenin phosphorylated by GSK3 (S33/37/T41) are localized at the AIS and are new components of this essential neuronal domain.

Colocalization of α-actinin and synaptopodin in the pyramidal cell axon initial segment.

The cisternal organelle that resides in the axon initial segment (AIS) of neocortical and hippocampal pyramidal cells is thought to be involved in regulating the Ca(2+) available to maintain AIS scaffolding proteins, thereby preserving normal AIS structure and function. Through immunocytochemistry and correlative light and electron microscopy, we show here that the actin-binding protein α-actinin is present in the typical cistenal organelle of rodent pyramidal neurons as well as in a large structure in the AIS of a subpopulation of layer V pyramidal cells that we have called the "giant saccular organelle." Indeed, this localization of α-actinin in the AIS is dependent on the integrity of the actin cytoskeleton.

In vitro maturation of the cisternal organelle in the hippocampal neuron's axon initial segment.

Regulation of Ca(2+) concentrations is essential to maintain the structure and function of the axon initial segment (AIS). The so-called cisternal organelle of the AIS is a structure involved in this regulation, although little is known as to how this organelle matures and is stabilized. Here we describe how the cisternal organelle develops in cultured hippocampal neurons and the interactions that facilitate its stabilization in the AIS.

Casein kinase 2 and microtubules control axon initial segment formation.

The axon initial segment (AIS) is a unique axonal subdomain responsible for the generation of the neuronal action potential and the maintenance of the axon-dendritic functional polarity. Despite its importance, the mechanisms controlling AIS development and maintenance remain largely unknown. Here we show that the AIS microtubule cytoskeleton is composed of a pool of more stable, detergent resistant, microtubules.

New role of IKK alpha/beta phosphorylated I kappa B alpha in axon outgrowth and axon initial segment development.

Neuronal polarity development begins by the outgrowth of the axon and the formation of the axon initial segment which acts as a diffusion barrier and it is the place of action potential generation. The mechanisms controlling this development are largely unknown. We describe a role for IkappaB alpha, the NFkappaB inhibitor, in the initial stages of axon outgrowth and the development of the axon initial segment.