title: Synapsin I and syntaxin 1B: key elements in the control of neurotransmitter release are regulated by neuronal activation and long-term potentiation in vivo.
abstract: The messenger RNAs encoding proteins of the exocytotic machinery were measured at different times following the induction of long-term potentiation or increasing neuronal activity in the dentate gyrus of the rat in vivo. In situ hybridization revealed that from the many messenger RNAs that encode proteins involved in regulated exocytosis, only those encoding synapsin I and syntaxin 1B were specifically increased. The levels of messenger RNA encoding both synapsin I and syntaxin 1B were increased on the ipsilateral side of the dorsal dentate gyrus 2 and 5 h following the induction of long-term potentiation. Syntaxin 1B was also increased in the ventral dentate gyrus at the same time-points. On the contralateral side of the dentate gyrus there was an increase in both synapsin I and syntaxin 1B at 5 h only. All of these long-term potentiation-induced changes were prevented when the tetanus was delivered in the presence of the N-methyl-D-aspartate receptor antagonist. (D(-)-2-amino-5-phosphonopentanoic acid. Immunocytochemical staining revealed that protein levels for both synapsin I and syntaxin 1B were elevated in the mossy fibre terminal zone of CA3 5 h after the induction of long-term potentiation. In addition to these plasticity-induced changes, a transient increase in the messenger RNA encoding syntaxin 1B was observed at 2 h in conditions of high intensity stimulation of the perforant path to increase the level of cellular activation, but this change was not maintained even when high intensity stimulation was sustained for 5 h. No changes in either of the messenger RNAs were observed under low frequency stimulation and pseudotetanus at either time-points. These results show that an overall increase in neuronal excitation within a neuronal network can be differentiated from a change in synaptic strength at a specific subset of the synapses, where only synaptic plasticity leads to long-term changes in the expression of selective members of the exocytotic machinery. Altered concentrations of key vesicle proteins may thus provide the means for modulation of neurotransmitter release over long time-periods. The persistent long-term potentiation-induced postsynaptic increase in messenger RNAs encoding these presynaptic proteins has important implications for the propagation of signals downstream from the site of long-term potentiation induction in hippocampal neural networks, and highlights a candidate molecular mechanism for mediating the propagation of synaptic plasticity in such networks.
authors.affiliation: Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR C9923, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Hicks
authors.forename: S
authors.initials: S
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Rodger
authors.forename: A
authors.initials: A
authors.lastname: Helme-Guizon
authors.forename: S
authors.initials: S
authors.lastname: Laroche
authors.forename: J
authors.initials: J
authors.lastname: Mallet
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism* / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000378:metabolism*; D050827:Syntaxin 1
chemical_list: D000954:Antigens, Surface; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D016704:Synapsins; D050827:Syntaxin 1