Lugaro cells

The cerebellum mostly contains interneurons. Purkinje cells are the well-known ganglion cells of the cerebellum which contain mostly GABA. Purkinje neurons form powerful inhibitory synapses on neurons in the deep cerebellar nuclei, which directly relay to spinal cord motoneurons. Therefore the inhibitory output of the cerebellum is important for sculpting motor behavior.

Lugaro cells are one class of interneuron in the cerebellum, which were first described by Lugaro in the early nineteenth century. The Lugaro cell is shown in red and Purkinje cells are yellow.

From Lugaro cells

The neuron of Lugaro has been described in the granular layer of various species of mammals including humans. Lugaro neurons are found just inferior to the Purkinje (p) cell bodies. They are positioned between the molecular (m) and granular (g) layers of the cerebellum.

From Lugaro cells

Lugaro cells have thick principal dendrites that emerge from opposite poles of the cell body and extend for remarkably long distances, up to 230-300 um, along the boundary between the Purkinje neuron layer and granular layer. The dendrites appear to contact 5-15 Purkinje cell bodies in a horizontal direction.

Like the dendrites of olfactory and taste sensory neurons, Lugaro cells exhibit specialized dendrites with the ability to sense nearby chemical or mechanical stimuli, therefore Sotnikov included Lugaro cells in a list of possible bipolar sensory neurons, based on morphological criteria. The dendrites of Lugaro cells form an extensive receptive surface that monitors the chemical and physical environment in the vicinity of Purkinje cells. Since its dendrites contact 5-15 Purkinje cells bodies in a horizontal direction, and receive inputs from recurrent branches of Purkinje neuron axons, the Lugaro cells appears to have a role in the sampling and integration of the outputs converging from neighbouring Purkinje cells.

In some instances, Lugaro cells form clusters of 2-5 tightly packed cells. Golgi staining revealed 2 or 3 Lugaro cells impregnated near each other. This dye-coupling could be explained if the dendrites of Lugaro cells contain electrical synapses through which the dye may pass in a bidirectional manner. Lugaro cell dendrites, like other primary sensory neurons of the brain, may form bundles that are connected via electrical synapses and gap junctions at dendrosomatic and dendrodendritic junctions.

The horizontally disposed basket cell axons in the supraganglionic plexus occupy the layer superior to the Purkinje cells. The layer inferior to the Purkinje cell layer is known as the infraganglionic plexus. Lugaro cell dendrite bundles course through the infraganglionic plexus, forming a sheet adjacent to the ganglion neurons of the cerebellum, much like the dendrites of TRN neurons form a layer dorsal to the thalamus. Immunocytochemical investigations have demonstrated GAD or GABA immunoreactivity in the Lugaro cell of the rat and human, indicating its putative GABAergic, inhibitory nautre, and also the presence of the inhibitory amino acid glycine and of a co-localization of glycine and GABA.


Lugaro cell axon

Though little is known about Lugaro cells in general, it is thought that Lugaro cell axons target basket and stellate cells in the molecular layer. The major target of the Lugaro cell axon is the inferior 1/3 of the molecular layer, where the Lugaro cell axon runs with the parallel fibers, giving off branches in the molecular layer. Lugaro cell axon collaterals extend for quite a long distance in the latero-lateral direction, exactly parallel to the parallel fibers, as shown in the figure below.

Sometimes the Lugaro cell axon takes a curving route through the granule layer, before running its parallel course in the molecular layer. The axon dips through the granular layer, then the white matter, before ascending to terminate on basket or stellate cells in the molecular layer. In the figure below, the Lugaro cell axon passes through the white matter before ascending to terminate on target cells about 400 micrometers from the original cell soma. Notice the dendrites of the Lugaro cell are adjacent to Purkinje cell bodies.

The Lugaro cell axon also terminates on Golgi cells in the granular layer. In some cases, the Lugaro cell axon never reascends to the molecular layer in which case the Golgi neurons are its postsynaptic target. According to Dieudonne, the Lugaro cell forms a major input to Golgi cells, and one Lugaro cell may contact up to 100 Golgi cells.

From Lugaro cells

The figure above is a Lugaro cell from rat cerebellum that has been stained with the Golgi technique. The thick dendrites are confined to the region of Purkinje cell bodies. The axon, marked by a carrot, travels into the granular layer and cannot be followed any farther in this sample.

The next figure shows another Golgi-impregnanted Lugaro cell. The dendrites are restricted to the region of Purkine cells bodies, and the axon spreads to the molecular and granular zones.

From Lugaro cells

The Lugaro cells axon contacts exclusively inhibitory interneurons, including stellate, basket, and Golgi cells. The parallel axon preferentially contacts stellate and basket cells and the transverse axon contacts Golgi cells. The Lugaro cell is a key interneuron in the cerebellum, because it interconnects many neurons located in all cortex layers. It samples information at the level of the Purkinje cell axon collaterals and distributes information to the molecular and granular layers of cerebellum.

Lugaro cell electrophysiology

Very little is known about the electrophysiology of Lugaro neurons, because Lugaro cells are normally silent in cerebellar slice preparations. It has been reported that Lugaro cells are sensitive to 5-HT, although the significance of this finding is unclear since the cerebellum has comparatively little 5-HT compared to other brain regions. Lugaro cell excitation and subsequent Golgi cell inhibition can be evoked by submicromolar concentrations of 5-HT. Application of 5-HT to Lugaro cells triggered IPSPs on Golgi cells. The excitation of Lugaro cells by 5-HT could be inhibited by 10 uM ketanserin, showing the involvement of 5-HT2A receptors.

From Lugaro cells

Because of the well-known organization of the cerebellar system, Lugaro cells may represent valuable cellular models to analyze the function of Sotnikov's primary sensory neurons within the brain.


References

Laine J. and H. Axelrad. (1996). Morphology of the Golgi-impregnated Lugaro cell in the rat cerebellar cortex: a reappraisal with a description of its axon. J.Comp.Neurol. 375, 618-640.