Biology subjects

Silva-Cruz, A.

Publications and source records attributed to Silva-Cruz, A..

3 recordsLinked to original sources

bioRxiv2024

Postweaning development influences endogenous VPAC1 modulation of LTP induced by theta-burst stimulation: a link to maturation of the hippocampal GABAergic system?

Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous VIP acting on VPAC1 receptors strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC1 receptor levels are developmentally regulated during embryogenesis, its variation along postweaning development is unknow, as is VPAC1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by TBS (5x4) (5 bursts, 4 pulses delivered at 100Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC1 receptor antagonist PG 97-269 (100nM) on TBS-induced LTP was much larger in juvenile (3-week-old) than in young-adult (6-7-week-old) or adult (12-week-old) rats. This effect was not associated to a developmental decrease in synaptic VPAC1 receptor levels. However, an increase in pre and post synaptic GABAergic synaptic markers, suggests an increase in the number of GABAergic synaptic contacts that is more prominent than the one observed in glutamatergic connections during this period. Conversely, endogenous VPAC2 receptor activation did not significantly influence of TBS-induced LTP. VPAC2 receptor levels enhance pronouncedly during postweaning development, but not at synaptic sites. Given the involvement of VIP interneurons in several aspects of hippocampal-dependent learning, neurodevelopmental disorders, and epilepsy, this could provide important insights into the role of VIP modulation of hippocampal synaptic plasticity during normal and altered brain development potentially contributing to epileptogenesis.

neuroscience↗

bioRxiv2022

Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for lipid raft dynamics in early metaplasticity.

Non-epileptic seizures are identified as a common epileptogenic trigger. Early metaplasticity following seizures may contribute to epileptogenesis by abnormally altering synaptic strength and homeostatic plasticity. We now studied how in vitro epileptiform activity triggers early changes in CA1 long-term potentiation (LTP) induced by theta-burst stimulation (TBS) in rat hippocampal slices and the involvement of lipid rafts in these early metaplasticity events. Two forms of epileptiform activity (EA) were induced: 1) interictal-like EA triggered by withdrawal of Mg2+ and K+ elevation to 6mM in the superfusion medium or 2) ictal-like EA induced by bicuculine (10M) delivery. LTP induced 30 min post EA was impaired, an effect more pronounced after ictal-like EA. LTP recovered to control levels 60 min post interictal-like EA but was still impaired 60 min after ictal-like EA. The synaptic molecular events underlying this altered LTP were investigated 30 min post EA. Synaptosomes isolated from parallel slices showed enhanced AMPA GluA1 Ser831 phosphorylation but decreased Ser 845 phosphorylation and a marked decrease in GluA1/GluA2 ratio. A marked decrease in flotillin-1 and caveolin-1 levels concomitantly with a moderate increase in PSD-95 and marked increase in gephyrin levels. Altogether, EA differentially influences hippocampal CA1 LTP thorough regulation of GluA1/GluA2 levels and AMPA GluA1 phosphorylation suggesting altered LTP post-seizures may be a relevant target of antiepileptogenic therapies. In addition, this metaplasticity is also associated with marked alterations in classic and synaptic lipid raft markers, suggesting these may also constitute promising targets in epileptogenesis prevention.

neuroscience↗

bioRxiv2021

Cellular and molecular mechanisms involved in LTP induced by mild theta-burst stimulation in hippocampal slices from young male rats: from weaning to adulthood.

Long-term potentiation (LTP) is a highly studied cellular process yet determining the transduction and GABAergic pathways that are the essential vs. modulatory for LTP elicited by theta-burst stimulation (TBS) in the hippocampal CA1 area is still elusive, due to the use of different TBS intensities, patterns, or different rodent/cellular models. We now characterized the developmental maturation and the transduction and GABAergic pathways required for mild TBS-induced LTP in hippocampal CA1 area in male rats. LTP induced by TBS (5x4) (5 bursts of 4 pulses delivered at 100Hz) lasted for up to 3h and was increasingly larger from weaning to adulthood. Stronger TBS patterns - TBS (15x4) or three TBS (15x4) separated by 6 min induced nearly maximal LTP not being the best choice to study the value of LTP-enhancing drugs. LTP induced by TBS (5x4) in young adults was fully dependent on NMDA receptor and CaMKII activity but independent of PKA or PKC activity. Furthermore, it was partially dependent on GABAB receptor activation and was potentiated by GABAA receptor blockade and less by GAT-1 transporter blockade. AMPA GluA1 phosphorylation on Ser831 (CaMKII target) but not GluA1 Ser845 (PKA target) was essential for LTP expression. The phosphorylation of the Kv4.2 channel was observed at Ser438 (CaMKII target) but not at Thr602 or Thr607 (ERK/MAPK pathway target). This suggests that cellular kinases like PKA, PKC or kinases of the ERK/MAPK family although important modulators of TBS (5x4)-induced LTP may not be essential for its expression in the CA1 area of the hippocampus. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/440440v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@cf78caorg.highwire.dtl.DTLVardef@1031737org.highwire.dtl.DTLVardef@1e91d6corg.highwire.dtl.DTLVardef@18abe3b_HPS_FORMAT_FIGEXP M_FIG C_FIG LTP induced by theta-burst stimulation (TBS) in young adult male rat hippocampal CA1 area is increasingly more robust with the number of bursts and number of spaced TBS trains. LTP induced by TBS shows developmental maturation increasing potentiation from weaning to adulthood. Expression of LTP induced by mild TBS (5x4) in young adults requires NMDA receptor and CaMKII activity and AMPA Ser831 phosphorylation, but not PKA or PKC activity, and is likely curtailed by Kv4.2 Ser438 phosphorylation.

neuroscience↗