Discovery and rediscoveries of Golgi cells

When Camillo Golgi invented the black reaction in 1873 and first described the fine anatomical
structure of the nervous system, he described a ‘big nerve cell’ that later took his name, the
Golgi cell of cerebellum (‘Golgi’schen Zellen’, Gustaf Retzius, 1892). The Golgi cell was then
proposed as the prototype of type-II interneurons, which form complex connections and exert
their actions exclusively within the local network. Santiago Ram´on y Cajal (who received the
Nobel Prize with Golgi in 1906) proceeded to a detailed description of Golgi cellmorphological
characteristics, but functional insight remained very limited formany years. The first rediscovery
happened in the 1960s, when neurophysiological analysis in vivo revealed that Golgi cells
are inhibitory interneurons. This finding promoted the development of two major cerebellar
theories, the ‘beam theory’ of John Eccles and the ‘motor learning theory’ of David Marr,
in which the Golgi cells regulate the spatial organisation and the gain of input signals to be
processed and learned by the cerebellar circuit. However, the matter was not set and a series of
pioneering observations using single unit recordings and electronmicroscopy raised new issues
that could not be fully explored until the 1990s. Then, the advent of new electrophysiological
and imaging techniques in vitro and in vivo demonstrated the cellular and network activities
of these neurons. Now we know that Golgi cells, through complex systems of chemical and
electrical synapses, effectively control the spatio-temporal organisation of cerebellar responses.
The Golgi cells regulate the timing and number of spikes emitted by granule cells and coordinate
their coherent activity. Moreover, the Golgi cells regulate the induction of long-term synaptic
plasticity along the mossy fibre pathway. Eventually, the Golgi cells transform the granular
layer of cerebelluminto an adaptable spatio-temporal filter capable of performing several kinds
of logical operation. After more than a century, Golgi’s intuition that the Golgi cell had to
generate under a new perspective complex ensemble effects at the network level has finally been
demonstrated.