Changes in the synaptic strength of neurons, effected by repeated neuronal activity, drive important behavioral processes such as learning and memory. Continuous simulation of a neuron, for example, can alter the signaling or molecular architecture at its synapses, and make it easier—or harder—for that neuron to activate other neurons with which it communicates.
Synaptic efficacy can be enhanced by increasing the process known as excitatory neurotransmission, or by decreasing its opposing process, inhibitory neurotransmission. These processes trigger or halt the firing of neurons, respectively. Now, an international team of researchers, including Hiroko Bannai at the RIKEN Brain Science Institute in Wako, has shown that neuronal activity drives inhibitory neurotransmitter receptors to diffuse away from the synapse, which substantially reduces inhibitory neurotransmission at those synapses1.
In many parts of the brain, inhibitory neurotransmission is mediated by a molecule called γ-aminobutyric acid (GABA) binding to its receptors at synapses. When the researchers induced neuronal activity in cultured neurons, they found fewer GABA receptors—and fewer GABA receptor scaffolding molecules—at the synapses of these neurons. This resulted in less efficient inhibitory neurotransmission owing to smaller inhibitory electrical currents through these receptors.
To respond to GABA molecules, GABA receptors must be on the surface of the neuron. But neuronal activity did not change the levels of GABA receptors that were on the surface or that were inside the neuron. Instead, when the researchers labeled the GABA receptors and watched them move, they found that induction of neuronal activity enhanced the diffusion of the receptors along the surface of the neuron. Importantly, it seemed that greater GABA receptor diffusion caused by neuronal activity reduced the amount of time that the GABA receptors spent at the synapse (Fig. 1, click on link below). This could explain why neuronal activity caused a decrease in inhibitory neurotransmission.
The investigators obtained these results in neurons from the hippocampus, a part of the brain involved in spatial learning. However, other reports have shown that neuronal activity can reduce diffusion and enhance synaptic targeting of receptors for a different inhibitory neurotransmitter called glycine in neurons from the spinal cord. This suggests that different cell types—and different receptors—may respond to neuronal activity in totally different ways.
These findings indicate that “lateral diffusion, regulated through interactions between receptors and their scaffolding proteins, could provide a simple mechanism for rapid and reversible activity-dependent modulation of synaptic strength,” says Bannai. “Next, we plan to elucidate the detailed molecular mechanisms controlling receptor diffusion dynamics.”
Reference
1. Bannai, H., Lévi, S., Schweizer, C., Inoue, T., Launey, T., Racine, V., Sibarita, J-B., Mikoshiba, K. & Triller, A. Activity-dependent tuning of inhibitory neurotransmission based on GABAAR diffusion dynamics. Neuron 62, 670–682 (2009).
The corresponding author for this highlight is based at the RIKEN Laboratory for Developmental Neurobiology
