At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

• DOI: 10.1523/jneurosci.5019-08.2009
• Publication Date: 2009-02-25T18:34:19Z
• Authors: Sudhir Sivakumaran; Majid H. Mohajerani; Enrico Cherubini
• Keywords: Neurons; 0301 basic medicine; Patch-Clamp Techniques; Brain-Derived Neurotrophic Factor; Action Potentials; In Vitro Techniques; Synaptic Potentials; Cyclic AMP-Dependent Protein Kinases; Hippocampus; Synaptic Transmission; Electric Stimulation; Rats; 03 medical and health sciences; Animals, Newborn; Sodium Potassium Chloride Symporter Inhibitors; Mossy Fibers, Hippocampal; Synapses; Animals; Calcium; Enzyme Inhibitors; Rats, Wistar; Bumetanide

In the adult rat hippocampus, axons of granule cells in dentate gyrus, mossy fibers (MF), form excitatory glutamatergic synapses with CA3 principal cells. neonates, MF release into their targets mainly GABA, which at this developmental stage is depolarizing. Here we tested hypothesis that, immature MF–CA3 synapses, correlated presynaptic [single fiber-evoked GABA A -mediated postsynaptic potentials (GPSPs)] and activity (back propagating action potentials) may exert a critical control on synaptic efficacy. This plasticity, called spike-timing-dependent plasticity (STDP), Hebbian type learning extensively studied level synapses. Depending relative timing, pairing spiking single MF-GPSPs induced bidirectional changes case positive pairing, spike-timing-dependent-long-term potentiation (STD-LTP) was associated persistent increase GPSP slope probability cell firing. The transduction pathway involved rise calcium combined cAMP-dependent PKA (protein kinase A) brain-derived neurotrophic factor (BDNF). Retrograde signaling via BDNF TrkB receptors led to release. “presynaptically” silent neurons, enhanced by protocol, unsilenced these Shifting E from depolarizing hyperpolarizing direction bumetanide failed modify strength. Thus, STD-LTP GPSPs provides reliable way convey information associative network time when are still poorly developed.