Differential expression of the c-fos protein and synaptophysin in zebrin II positive and zebrin II negative cerebellar cortical areas in 4-aminopyridine seizures

Abstract

The present study examined temporal activation patterns of rat cerebellar cortical neurons in 4-aminopyridine induced seizures, using c-fos protein as a marker of neuronal activity. C-fos-containing cells were counted in each cerebellar cortical layer, and cell count was compared between zebrin II positive and zebrin II negative bands of the lobules of the vermis and cerebellar hemispheres. We found significant activation of granule cells and interneurons of the molecular layer in zebrin II positive bands. The Purkinje cells, in contrast, exhibited non-significant, scattered c-fos immunoreactivity across all bands.Fluctuation of synaptophysin expression in the mossy fibre rosettes of the granular layer was determined via light microscopic immunohistochemistry. We detected a transient, significant decrease in synaptophysin staining density following 4-aminopyridine seizures, which may indicate short-term synaptic depression. We also identified different timing of increased c-fos expression in the neurons of the cerebellar cortex in different cortical zones. In particular, the activation pattern of the interneurons of the molecular layer reflected the climbing fibre distribution, reflecting the zonal olivo-cortico-nuclear organization. Seizure-induced activation of the granule cells corresponded with the zebrin II positive zones. This observation raises the possibility that zebrin II positive compartments may be more susceptible to cerebellar convulsions.

Immediate Early Gene c-fos in the Brain: Focus on Glial Cells

“…To our knowledge, c-fos was initially used in brain research to measure the neural activity after seizures. In this area, it allowed researchers, for example, to map the neuronal pathways involved in different models/intensities of the seizure [ 38 , 39 , 40 ]; to estimate the effect of antiepileptic drugs [ 41 ]; or to analyze new-born cells and asymmetries after seizures [ 42 , 43 ]. c-fos has also been consolidated as a reliable marker for cell activation derived from learning [ 14 ] and memory [ 44 , 45 ].…”

Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons

“…4AP represents an ideal tool for our study, since it is a potent inhibitor of voltage-gated potassium (Kv) channels, and it causes an increase in intracellular Ca 2+ and synaptic exocytosis ( Bostock et al, 1981 ; Mihaly et al, 2001 ). 4AP activity can also be monitored by analysing the expression of the immediate early gene c-fos , which is increased upon neuronal stimulation ( Bullitt, 1990 ; Herdegen and Leah, 1998 ; Krisztin-Peva et al, 2019 ; Toth et al, 2018 ; Willoughby et al, 1995 ). Importantly, the secretion P301S hTau was significantly decreased by treating neurons with BoNT/A, whereas the release of WT hTau remained unaffected ( Fig.…”

Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons

“…4AP represents an ideal tool for our study, since it is a potent inhibitor of voltagegated potassium (Kv) channels, and it causes an increase in intracellular Ca 2+ and synaptic exocytosis (Bostock et al, 1981; Mihaly et al, 2001). 4AP activity can also be monitored by analysing the expression of the immediate early gene c-fos , which is increased upon neuronal stimulation (Bullitt, 1990; Herdegen & Leah, 1998; Krisztin-Peva et al, 2019; Toth et al, 2018; Willoughby et al, 1995). Importantly, the secretion P301S hTau was significantly decreased by treating neurons with BoNT/A, whereas the release of WT hTau remained unaffected ( Figure 4B ).…”