BDNF up-regulates evoked GABAergic transmission in developing hippocampus by potentiating presynaptic N- and P/Q-type Ca2+ channels signalling.
Chronic application of brain-derived neurotrophic factor (BDNF) induces new selective synthesis of non-L-type Ca2+ channels (N, P/Q, R) at the soma of cultured hippocampal neurons. As N- and P/Q-channels support neurotransmitter release in the hippocampus, this suggests that BDNF-treatment may enhance synaptic transmission by increasing the expression of presynaptic Ca2+ channels as well. To address this issue we studied the long-term effects of BDNF on miniature and stimulus-evoked GABAergic transmission in rat embryo hippocampal neurons. We found that BDNF increased the frequency of miniature currents (mIPSCs) by approximately 40%, with little effects on their amplitude. BDNF nearly doubled the size of evoked postsynaptic currents (eIPSCs) with a marked increase of paired-pulse depression, which is indicative of a major increase in presynaptic activity. The potentiation of eIPSCs was more relevant during the first two weeks in culture, when GABAergic transmission is depolarizing. BDNF action was mediated by TrkB-receptors and had no effects on: (i) the amplitude and dose-response of GABA-evoked IPSCs and (ii) the number of GABA(A) receptor clusters and the total functioning synapses, suggesting that the neurotrophin unlikely acted postsynaptically. In line with this, BDNF affected the contribution of voltage-gated Ca2+ channels mediating evoked GABAergic transmission. BDNF drastically increased the fraction of evoked IPSCs supported by N- and P/Q-channels while it decreased the contribution associated with R- and L-types. This selective action resembles the previously observed up-regulatory effects of BDNF on somatic Ca2+ currents in developing hippocampus, suggesting that potentiation of presynaptic N- and P/Q-channel signalling belongs to a manifold mechanism by which BDNF increases the efficiency of stimulus-evoked GABAergic transmission.
Baldelli
P
P
INFM Research Unit, University of Turin, I-10125 Turin, Italy.
Novara
M
M
Carabelli
V
V
Hernández-Guijo
J M
JM
Carbone
E
E
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D020813:Receptor, trkB