BDNF has opposite effects on the quantal amplitude of pyramidal neuron and interneuron excitatory synapses.
Recently, we have identified a novel form of synaptic plasticity that acts to stabilize neocortical firing rates by scaling the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of neuronal activity. Here, we show that the effects of activity blockade on quantal amplitude are mediated through the neurotrophin brain-derived neurotrophic factor (BDNF). Exogenous BDNF prevented, and a TrkB-IgG fusion protein reproduced, the effects of activity blockade on pyramidal quantal amplitude. BDNF had opposite effects on pyramidal neuron and interneuron quantal amplitudes and modified the ratio of pyramidal neuron to interneuron firing rates. These data demonstrate a novel role for BDNF in the homeostatic regulation of excitatory synaptic strengths and in the maintenance of the balance of cortical excitation and inhibition.
Department of Biology and Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA.
L C
LC
Rutherford
S B
SB
Nelson
G G
GG
Turrigiano
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D011789:Quantum Theory; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014793:Visual Cortex / Q000166:cytology / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D007074:Immunoglobulin G; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D020794:Receptor Protein-Tyrosine Kinases