Medical/biological study (experimental study)

GABA(B) receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses med./bio.

By: Xu C, Zhao MX, Poo MM, Zhang XH

Published in: Nat Neurosci 2008; 11 (12): 1410-1418

The article deals with synaptic plasticity. Synapses undergo activity-dependent changes of their ultrastructure. These changes of synaptic connections are referred to as synaptic plasticity which is the basis of learning and memory processes.
The aim of this study was to investigate the role for GABA_B receptors in frequency-dependent long-term synaptic modifications of developing GABA-ergic synapses on hippocampal CA1 pyramidal cells (the frequency of synaptic stimulation is critical for determining the polarity of long-term modification of excitatory synapses).

The author's attention was focused on the developing rat hippocampal synapses during the first few postnatal weeks, a period in which GABA-ergic synapses may undergo extensive activity-dependent refinement.
GABA_B receptors are largely located in extrasynaptic sites and can be activated by GABA spillover during high frequency GABA-ergic synaptic activity. Activity-induced synaptic modification can be attributed to changes in either the amount of evoked neurotransmitter release or the postsynaptic response to the released neurotransmitter, or both.

Exposure	Parameters
Exposure 1: 1–50 Hz Exposure duration: 100 pulses	I = 5 - 100 µA for presynaptic spikes I = 2 mA for postynaptic spikes

Frequency	1–50 Hz
Type	electric field
Waveform	pulsed
Exposure duration	100 pulses
Additional info	presynaptic spikes: pulse width = 100 µs postsynaptic spikes: pulse width = 2 ms

Exposure source	pulse generator + bipolar tungsten electrode

Measurand	Value	Type	Method	Mass	Remarks
cf. remarks	-	-	-	-	I = 5 - 100 µA for presynaptic spikes
cf. remarks	-	-	-	-	I = 2 mA for postynaptic spikes

Exposed system:

Investigated system:

Time of investigation:

The data showed that long-term modification of developing rat hippocampal GABA-ergic synapses that was induced by repetitive coincident presynaptic and postsynaptic spiking (i.e. coincident stimulation of the presynaptic and postsynaptic cell) was frequency dependent. Spiking at 20-50 Hz resulted in synaptic potentiation, whereas spiking at 5 Hz led to synaptic depression. The long-term potentiation was abolished by pharmacological blocking GABA_B receptors, whereas the depression was independent of GABA_B receptors activation and could be converted to potentiation by elevating GABA_B receptors activity.
The potentiation could be attributed to a local postsynaptic increase in Na⁺/K⁺/2Cl^- co-transporter activity near activated synapses. The activity of postsynaptic Ca²⁺/calmodulin-dependent protein kinase II was necessary for long-term potentiation of these developing GABA-ergic synapses.
Together with the data that activation of GABA_B receptors is frequency dependent, these results indicate that postsynaptic GABA_B receptors activation mediates frequency-dependent potentiation of developing GABA-ergic synapses. The results extend the knowledge of the function of GABA_B receptors to the postsynaptic regulation of long-term synaptic plasticity of developing GABA-ergic synapses.

Study character:

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