| Autor: |
Gil M; BioISI-Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal., Caulino-Rocha A; BioISI-Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal., Bento M; BioISI-Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal., Rodrigues NC; Unidade de Neurociências, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal., Silva-Cruz A; Unidade de Neurociências, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal., Ribeiro JA; Unidade de Neurociências, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal.; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal., Cunha-Reis D; BioISI-Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisbon, Portugal.; Unidade de Neurociências, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal.; Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal. |
| Abstrakt: |
Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous vasoactive intestinal peptide (VIP) acting on its VPAC 1 receptor strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC 1 receptor levels are developmentally regulated during embryogenesis, their variation along postweaning development is unknown, as is the VPAC 1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC 1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by mild TBS (5 bursts, 4 pulses delivered at 100 Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC 1 receptor antagonist PG 97-269 (100 nM) 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 with a developmental decrease in synaptic VPAC 1 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 VPAC 2 receptor activation did not significantly influence TBS-induced LTP. VPAC 2 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. |
