Abstract
Brain Derived Neurotrophic Factor (BDNF) signalling contributes to the formation, maturation and plasticity of Central Nervous System (CNS) synapses. Acute exposure of cultured brain circuits to BDNF leads to up-regulation of glutamatergic neuro-transmission, by the accurate tuning of pre and post synaptic features, leading to structural and functional synaptic changes. Chronic BDNF treatment has been comparatively less investigated, besides it may represent a therapeutic option to obtain rescue of post-injury alterations of synaptic networks. In this study, we used a paradigm of BDNF long-term (4 days) incubation to assess in hippocampal neurons in culture, the ability of such a treatment to alter synapses. By patch clamp recordings we describe the augmented function of excitatory neurotransmission and we further explore by live imaging the presynaptic changes brought about by long-term BDNF. In our study, exogenous long-term BDNF exposure of post-natal neurons did not affect inhibitory neurotransmission. We further compare, by genetic manipulations of cultured neurons and BDNF release, intracellular overexpression of this neurotrophin at the same developmental age. We describe for the first-time differences in synaptic modulation by BDNF with respect to exogenous or intracellular release paradigms. Such a finding holds the potential of influencing the design of future therapeutic strategies.
Highlights
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family crucial to brain and spinal cord development [1, 2]
Long-term BDNF treatment improves excitatory synaptic current frequency and amplitude To investigate the ability of prolonged exposure to BDNF to regulate network dynamics and synaptic transmission, dissociated hippocampal cultures were treated for 4 days with 20 nM mature BDNF and compared to untreated ones
Neuronal passive properties were routinely measured in Control neurons (n = 44) and BDNF-treated ones (n = 75) which did not differ in terms of cell capacitance (78 ± 5 pF in Control and 96 ± 6 pF in BDNF-treated), input resistance (500 ± 53 MΩ Control and 477 ± 47 MΩ) and resting membrane potential (− 47 ± 1 mV for Control and − 50 ± 1 mV for BDNF-treated)
Summary
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family crucial to brain and spinal cord development [1, 2]. BDNF promotes the formation of both excitatory and inhibitory synapses and increases their maturation [7]. Among the members of the neurotrophin family, BDNF stands out for its ability to regulate synaptic plasticity and various cognitive functions of the brain [8]. BDNF, when acutely delivered, has been shown to affect synaptic transmission and plasticity [9,10,11]. BDNF modulates inhibitory transmission, albeit through different mechanisms [20, 21]. BDNF potentiates excitatory synapses via pre- and post-synaptic mechanisms [22, 23]. BDNF increases glutamate release, enhancing the frequency of miniature excitatory postsynaptic currents (mEPSCs)
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