The cerebellum is one of the brain areas involved in learning and memory formation. Long-term synaptic plasticity is thought to play a pivotal role in supporting these functions. Moreover immediate Early Genes (IEGs) expression and de novo proteinsynthesis and/or modifi cation have been strictly associated with maintenance of Long-Term Potentiation (LTP) as well as memory consolidation and storage. Two highly conserved signalling cascades, PKA and MAPK, seem to be involved in earlytolate-LTP conversion; both pathway can activate CREB transcription factor through phosphorylation and P-CREB has been suggested to initiate the protein synthesisleading to late-LTP induction. The transcription factor c-fos is known to be rapidly and transiently induced in the Nervous System by a variety of stimuli and is thoughtto be directly involved in processes of neuronal plasticity including LTP. We used rat parasagittal cerebellar slices as a model system in which specific patterns of stimulation delivered to the mossy fi bers can induce both Long-Term Potentiationand Long-Term Depression (LTD), depending on local inhibition and other regulating factors. Using Voltage Sensitive Dye (VSD) imaging we obtained high-resolution maps of the spatial distribution of LTP/LTD induced from a Teta Burst Stimulus (TBS)application. Control and stimulated slices were fi xed at diff erent times from the TBS application and processed for in situ hybridization or immunohystochemistry in orderto detect IEGs mRNA expression patterns and protein expression/modifications. The expression pattern of c-fos and CREB mRNAs and their protein distribution and/or phosphorylation were then correlated with LTP/LTD maps generated by VSD imaging. Preliminary data indicate a signifi cant increase of P-CREB in the granular layersuggesting that CREB phosphorylation is induced as early as 15 minutes post TBS application. In situ hybridization experiments indicate a good correlation between c-fos and CREB mRNAs up-regulation and LTP distribution at 120 minutes post TBS. At the protein level, the comparison of immunofl uorescence signals and VSD immaging data indicate a clear correlation between c-Fos and P-CREB distribution and synaptic plasticity patterns.We are planning further experiments to confi rm these data and to test our experimental system in the presence of drugs that could interfere with the transcription, translation or post-translational protein regulation.

Immediate early genes regulation in rat cerebellar cortex during long-term synaptic plasticity induction / Polimeni, M.; Gandolfi, D.; Cerri, S.; Mapelli, Jonathan; Tritto, S.; Alloni, M.; Armentero, M. T.; Blandini, F.; D’Angelo, E.. - In: ITALIAN JOURNAL OF ANATOMY AND EMBRYOLOGY. - ISSN 1122-6714. - ELETTRONICO. - 116, No 1 (Supplement) 2011:(2011), pp. 147-147. (Intervento presentato al convegno 65° Congresso Nazionale della Società Italiana di anatomia ed Istologia tenutosi a Padova nel 27/09/2011-29/09/2011).

Immediate early genes regulation in rat cerebellar cortex during long-term synaptic plasticity induction

D. Gandolfi;MAPELLI, Jonathan;
2011

Abstract

The cerebellum is one of the brain areas involved in learning and memory formation. Long-term synaptic plasticity is thought to play a pivotal role in supporting these functions. Moreover immediate Early Genes (IEGs) expression and de novo proteinsynthesis and/or modifi cation have been strictly associated with maintenance of Long-Term Potentiation (LTP) as well as memory consolidation and storage. Two highly conserved signalling cascades, PKA and MAPK, seem to be involved in earlytolate-LTP conversion; both pathway can activate CREB transcription factor through phosphorylation and P-CREB has been suggested to initiate the protein synthesisleading to late-LTP induction. The transcription factor c-fos is known to be rapidly and transiently induced in the Nervous System by a variety of stimuli and is thoughtto be directly involved in processes of neuronal plasticity including LTP. We used rat parasagittal cerebellar slices as a model system in which specific patterns of stimulation delivered to the mossy fi bers can induce both Long-Term Potentiationand Long-Term Depression (LTD), depending on local inhibition and other regulating factors. Using Voltage Sensitive Dye (VSD) imaging we obtained high-resolution maps of the spatial distribution of LTP/LTD induced from a Teta Burst Stimulus (TBS)application. Control and stimulated slices were fi xed at diff erent times from the TBS application and processed for in situ hybridization or immunohystochemistry in orderto detect IEGs mRNA expression patterns and protein expression/modifications. The expression pattern of c-fos and CREB mRNAs and their protein distribution and/or phosphorylation were then correlated with LTP/LTD maps generated by VSD imaging. Preliminary data indicate a signifi cant increase of P-CREB in the granular layersuggesting that CREB phosphorylation is induced as early as 15 minutes post TBS application. In situ hybridization experiments indicate a good correlation between c-fos and CREB mRNAs up-regulation and LTP distribution at 120 minutes post TBS. At the protein level, the comparison of immunofl uorescence signals and VSD immaging data indicate a clear correlation between c-Fos and P-CREB distribution and synaptic plasticity patterns.We are planning further experiments to confi rm these data and to test our experimental system in the presence of drugs that could interfere with the transcription, translation or post-translational protein regulation.
2011
116, No 1 (Supplement) 2011
147
147
Polimeni, M.; Gandolfi, D.; Cerri, S.; Mapelli, Jonathan; Tritto, S.; Alloni, M.; Armentero, M. T.; Blandini, F.; D’Angelo, E.
Immediate early genes regulation in rat cerebellar cortex during long-term synaptic plasticity induction / Polimeni, M.; Gandolfi, D.; Cerri, S.; Mapelli, Jonathan; Tritto, S.; Alloni, M.; Armentero, M. T.; Blandini, F.; D’Angelo, E.. - In: ITALIAN JOURNAL OF ANATOMY AND EMBRYOLOGY. - ISSN 1122-6714. - ELETTRONICO. - 116, No 1 (Supplement) 2011:(2011), pp. 147-147. (Intervento presentato al convegno 65° Congresso Nazionale della Società Italiana di anatomia ed Istologia tenutosi a Padova nel 27/09/2011-29/09/2011).
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