Increased number of synaptic GABA(A) receptors underlies potentiation at hippocampal inhibitory synapses.
Changes in synaptic efficacy are essential for neuronal development, learning and memory formation and for pathological states of neuronal excitability, including temporal-lobe epilepsy. At synapses, where there is a high probability of opening of postsynaptic receptors, all of which are occupied by the released transmitter, the most effective means of augmenting postsynaptic responses is to increase the number of receptors. Here we combine quantal analysis of evoked inhibitory postsynaptic currents with quantitative immunogold localization of synaptic GABA(A) receptors in hippocampal granule cells in order to clarify the basis of inhibitory synaptic plasticity induced by an experimental model of temporal-lobe epilepsy (a process known as kindling). We find that the larger amplitude (66% increase) of elementary synaptic currents (quantal size) after kindling results directly from a 75% increase in the number of GABA(A) receptors at inhibitory synapses on somata and axon initial segments. Receptor density was up by 34-40% and the synaptic junctional area was expanded by 31%. Presynaptic boutons were enlarged, which may account for the 39% decrease in the average number of released transmitter packets (quantal content). Our findings establish the postsynaptic insertion of new GABA(A) receptors and the corresponding increase in postsynaptic responses augmenting the efficacy of mammalian inhibitory synapses.
Nusser
Z
Z
Medical Research Council, Department of Pharmacology, University of Oxford, UK.
Hájos
N
N
Somogyi
P
P
Mody
I
I
D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D004594:Electrophysiology; D005071:Evoked Potentials; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D007124:Immunoenzyme Techniques; D007696:Kindling, Neurologic / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D011963:Receptors, GABA-A