Glial cells promote dendrite formation and the reception of synaptic input in Purkinje cells from postnatal mice

Abstract

Previous studies suggest that glial cells contribute to synaptogenesis in specific neurons from the postnatal CNS. Here, we studied whether this is true for Purkinje cells (PCs), which represent a unique neuronal cell type due to their large size, massive synaptic input, and high vulnerability. Using new glia-free cultures enriched in PCs from postnatal mice we show that these neurons survived and grew, but displayed only low levels of excitatory and inhibitory synaptic activity. Coculture with glial cells strongly enhanced the frequency and size of spontaneous and miniature excitatory synaptic currents as well as neurite growth and branching. Immunocytochemical staining for microtubule-associated protein 2- (MAP2-) positive neurites revealed impaired dendrite formation in PCs under glia-free conditions, which can explain the absence of synaptic activity. Glial signals strongly enhanced dendritogenesis in PCs and thus their ability to receive excitatory synaptic input from granule cells (GCs). The enhancement of dendrite formation was mimicked by glia-conditioned medium (GCM), whereas the increase in synaptic activity required physical presence of glia. This indicated that dendrite development is necessary but not sufficient for PCs to receive excitatory synaptic input and that synaptogenesis requires additional signals. The level of inhibitory synaptic activity was low even in cocultures due to a low incidence of inhibitory interneurons. Taken together, our results reinforce the idea that glial cells promote synaptogenesis in specific neuronal cell types.

Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment

“…An increased expression of this astroglial transporter in the molecular layer of the vermis may contribute to a glutamatergic hypofunction in an interplay between glia cells and neuronal dendrites. Glia cells are required for proper function and dendritogenesis of Purkinje cells and their ability to receive synaptic excitatory glutamatergic input from granule cells (Buard et al 2010), thus implicating an important role for SLC1A3 during neurodevelopment.…”

Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington’s disease

“…Cholesterol and glial-conditioned medium have a well-documented role in promoting axonal outgrowth in vitro under physiological conditions. Glial-derived lipoproteins containing cholesterol stimulate axon growth 27 and transcription of genes involved in dendrite and synapse development 28 in primary rat retinal ganglion cells; their co-culture with glial cells enhances synaptic activity and neurite outgrowth and branching in Purkinje neurons, 29 and cholesterol deficiency inhibits dendrite outgrowth in primary cortical and hippocampal neurons. 30 Impairments in astrocytic function are increasingly recognized as a culprit in neuronal dysfunction in neurodegenerative diseases, 31 such as amyotrophic lateral sclerosis, 32 Rett's syndrome, 33,34 lysosomal disorders, 35 Alzheimer's disease, 36 and HD.…”

Ontogênese de conexinas no cerebelo.

“…Além disso, o aumento da expressão de Cx43 ao longo do desenvolvimento cerebelar pode ser associado à maturação funcional de astrócitos. A presença de astrócitos foi associada à sinaptogênese em diferentes regiões do SNC (Buard et al, 2010). As primeiras sinapses do córtex cerebelar de galinha aparecem em E12 (Sepulveda et al, 2005).…”

“…A ausência da glia afeta a diferenciação das células de Purkinje in vitro (Buard et al, 2010). Existem evidências de que a glia de Bergmann guia a formação de conexões inibitórias de interneurônios da ML com as células de Purkinje (Ango et al, 2008).…”

“…De fato, o aparecimento dos transportadores de glutamato da glia de Bergmann coincide com o início do desenvolvimento dos dendritos secundários das células de Purkinje (Lordkipanidze e Dunaevsky, 2005). Além disso, os processos da glia de Bergmann são muito móveis durante o desenvolvimento cerebelar (Buard et al, 2010).…”