Study shows how astrocytes help control synapse strength and plasticity.
Whenever a person learns something new or is affected by their experiences it’s because synapses, the connections between neurons in the brain, have changed. Sometimes new synapses are made, and other times the strengths of existing synapses are turned up or down. When synapses are strengthened, the signal from one neuron to the next results in a bigger response than it used to, and vice versa. Until recently, synaptic strength was thought to change only at synapses of active presynaptic neurons. Now, a study from researchers at RIKEN has demonstrated that astrocytes help control the strength of connections between neurons. The team state that their study used cultured cells and brain slices to show that astrocytes in the hippocampus regulate changes in the brain brought on by neural activity. The study is published in the journal Proceedings of the National Academy of Sciences.
Previous studies show that dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. Astrocytes are a type of non-neural glial cell in the brain, often described as support cells for neurons, they have also been shown to regulate neuronal transmission. The current study examines the effects of astrocyte activity on synaptic strength and plasticity.
The current study used a culture of hippocampal neurons and astrocytes, in which two neurons were identified that each connected to a third target neuron at a separate synapse and were not connected with each other. Results show expected changes in synaptic strength at a synapse when the presynaptic neuron connected to it was stimulated with electrical pulses. Data findings show that this was often accompanied by changes at the other, non-stimulated, synapse.
Results show that the changes at these heterosynapses were not related to the postsynaptic neuron and were blocked by an NMDA receptor antagonist. Further testing showed that blocking astrocyte activity also prevented changes at the heterosynapses. The lab observed that blocking astrocyte NMDA receptors by any of several methods caused synaptic strengths of converging inputs on a given neuron to become more equal, whether in culture or in intact hippocampal slices. They go on to explain that this shows astrocyte activity helps maintain normal variation of synaptic strengths, even when strong, plasticity inducing stimulation is absent.
The team surmise that they have found an active mechanism that helps to increase variation in synaptic strength which originates from astrocytes, which have previously been thought to play mostly passive roles in the brain. They go on to add that as synaptic dysfunction is thought to trigger or exacerbate many neurological diseases, their work shows that astrocytes could be a potential target of novel therapeutics. For the future, the researchers state that their next goal is to determine the precise signaling mechanism by which astrocytes target presynapses, and whether communication between astrocytes is also involved in controlling synapse variability.