VIP enhances both pre- and postsynaptic GABAergic transmission to hippocampal interneurones leading to increased excitatory synaptic transmission to CA1 pyramidal cells.
Vasoactive intestinal peptide (VIP) is present in the hippocampus in three subtypes of GABAergic interneurones, two of which innervate preferentially other interneurones, responsible for pyramidal cell inhibition. We investigated how pre- and postsynaptic modulation of GABAergic transmission (to both pyramidal cells and interneurones) by VIP could influence excitatory synaptic transmission in the CA1 area of the hippocampus. VIP (0.1-100 nM) increased [(3)H]GABA release from hippocampal synaptosomes (maximum effect at 1 nM VIP; 63.8 +/- 4.0%) but did not change [(3)H]glutamate release. VIP (0.3-30 nM) enhanced synaptic transmission in hippocampal slices (maximum effect at 1 nM VIP; field excitatory postsynaptic potentials (epsp) slope: 23.7 +/- 1.1%; population spike amplitude: 20.3 +/- 1.7%). The action on field epsp slope was fully dependent on GABAergic transmission since it was absent in the presence of picrotoxin (50 microM) plus CGP55845 (1 microM). VIP (1 nM) did not change paired-pulse facilitation but increased paired-pulse inhibition in CA1 pyramidal cells (16.0 +/- 0.9%), reinforcing the involvement of GABAergic transmission in the action of VIP. VIP (1 nM) increased muscimol-evoked inhibitory currents by 36.4 +/- 8.7% in eight out of ten CA1 interneurones in the stratum radiatum. This suggests that VIP promotes increased inhibition of interneurones that control pyramidal cells, leading to disinhibition of synaptic transmission to pyramidal cell dendrites. In conclusion, concerted pre- and postsynaptic actions of VIP lead to disinhibition of pyramidal cell dendrites causing an enhancement of synaptic transmission.
Cunha-Reis
Diana
D
Institute of Pharmacology and Neurosciences, Faculty of Medicine and Institute of Molecular Medicine University of Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal. diana-reis@fm.ul.pt
Sebastião
Ana M
AM
Wirkner
Kerstin
K
Illes
Peter
P
Ribeiro
Joaquim Alexandre
JA
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014660:Vasoactive Intestinal Peptide; D005680:gamma-Aminobutyric Acid