Role of Spontaneous Activity in the Maturation of GABAergic Synapses in Embryonic Spinal Circuits
Spontaneous network activity (SNA) is displayed in many developing neural circuits shortly after synaptic connections form, and this activity is thought to be important for the maturation of the synaptic networks in which it is expressed. This chapter discusses the relationship between GABAergic signaling and SNA in the embryonic spinal cord. Spinal SNA consists of episodic bursts of spiking activity followed by quiescent periods. Episodes occur as a result of the highly excitable nature of these embryonic circuits. One of the important contributors to the excitable state of these developing networks is the depolarizing excitatory nature of GABAergic neurotransmission. This is due to high intracellular chloride levels in embryonic neurons, which set the GABAergic reversal potential (EGABA) to a level more depolarized than the resting potential. Recently, we have shown that SNA plays a role in adjusting the strength of immature spinal synapses through a general mechanism known as homeostatic plasticity. We propose that levels of SNA are homeostatically maintained through compensatory changes in synaptic strength. We find that the entire distribution of GABAergic miniature postsynaptic current (mPSC) amplitudes are increased by a multiplicative factor (scaled) after chronic blockade of SNA. We also have evidence that the scaling process is mediated by an increase in chloride accumulation.
KeywordsSynaptic Strength Spinal Neuron GABAergic Transmission GABAergic Synapse Intracellular Chloride
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