Glutamic acid decarboxylase immunoreactive large neuron types in the granular layer of the human cerebellar cortex

Abstract

'Non-traditional' large neurons of the granular layer of the cerebellar cortex include all its large neuronal types, except the Golgi neuron, which is instead one of the five 'classic' types of corticocerebellar neurons. The morphological, chemical and functional characteristics of the 'non-traditional' large neurons have not been entirely ascertained. The aim of this study was to ascertain whether morphological evidence can be provided of GABA synthesis within the 'non-traditional' large neurons of the human cerebellar cortex by means of immunocytochemistry for glutamic acid decarboxylase (GAD). Fragments of postmortem cerebellar cortex of various lobules from the hemispheres and vermis were studied. Immunoreactions revealed large neurons distributed throughout the granular layer in all lobules examined. They were discriminated by analyzing the morphological features of their bodies and processes and were identified as Golgi neurons and as some 'non-traditional' types, such as the candelabrum, Lugaro and synarmotic neurons. In addition, immunoreactive large neurons, with their bodies and processes closely adjacent to microvessels, were observed throughout the layer: these perivascular neurons could represent a new type of 'non-traditional' neuron of the cerebellar cortex. This study supplies the first indication that in the human cerebellar cortex some types of 'non-traditional' large neurons are GAD-immunoreactive, in addition to those neurons already known to be GABAergic (i.e., stellate, basket, Purkinje and Golgi neurons). These morphological data further point out possible functional roles for GABA as a neurotransmitter/neuromodulator in intrinsic, associative and projective circuits of the cerebellar cortex.

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

“…Indeed, candelabrum cells in the monkey (Macaca) cerebellum have recently been shown to be immunoreactive for glycine, GABA, and GAD (the GABA-synthesizing enzyme glutamate decarboxylase; Crook et al 2006), an observation in accord with the previous tentative identiWcation, in rats, of cells doubly reactive for GAD67 and the glycine transporter, Glyt2, as possibly comprising candelabrum cells (Tanaka and Ezure 2004). In human cerebellum, a cell-type which based on its location and the shape of its perikaryon may be classiWed as candelabrum cells were found to be GAD65/67 (the antibody used did not allow to distinguish isoforms; Flace et al 2004). Thus, current evidence concurs to indicate that candelabrum cells use GABA and glycine as transmitters.…”

Cerebellum- and forebrain-derived stem cells possess intrinsic regional character

“…The cerebellar neurons can be divided into the five 'classic' neuronal subtypes (granule cells, Golgi, stellate, basket neurons and Purkinje cells) and into the less common neuronal subtypes (Lugaro, brush and candelabrum neurons) (Flace et al, 2004;Laine and Axelrad, 1994).…”

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

“…In the Purkinje neuron layer, only GABAergic synapses are present, concentrated at the deep pole of the body of Purkinje neurons and formed by terminals of basket neuron axons [42-44]. In the granular layer, glutamatergic synapses and GABAergic synapses are both located in the neuropil regions scattered among granules (islands of Held), consisting of multiple synapses (glomeruli) established by glutamatergic terminals of mossy fibres and of axons of unipolar brush neurons [35-38,45] and GABAergic axon terminals of Golgi, candelabrum and Lugaro neurons [44,46,47], on granule dendrites.…”