EPFL neuroscientists have found that the output synapses of certain interneurons in the cortex show long-term plasticity. This plasticity occurs during a critical period of brain development and might contribute to the experience-dependent rewiring of brain circuits.
Interneurons inhibit the electrical activity of principal neurons in the cortex and other brain areas, by releasing the inhibitory neurotransmitter GABA. One class of interneurons, those that express the protein parvalbumin, mediate feed-forward inhibition in the sensory cortices. It is also known that the wiring of our main sensory cortices for hearing, vision and touch is “plastic”, meaning it can change in response to frequently experienced sensory impressions. This plasticity is strongest in children and young animals and is therefore called “critical-period plasticity”.
New research from EPFL’s Brain Mind Institute has looked at the plasticity of GABA-releasing synapses formed by parvalbumin-interneurons in the auditory cortex of mice. The team around Evan Vickers at Ralf Schneggenburger’s lab found a novel form of bi-directional plasticity that leads to either long-term depression or long-term potentiation of inhibition. Furthermore, they showed that the ability of parvalbumin interneurons to reduce their synaptic strength via long-term depression is lost with age and upon structured auditory sensory experience of the young mice.
Moreover, genetic removal of a GABA receptor that is involved in long-term depression of inhibition led to the disappearance of critical-period plasticity in the mice. “This suggests that a weakening of inhibition – as occurs after long-term depression of parvalbumin interneuron output synapses – could promote plasticity at excitatory synapses, and thereby initiate re-wiring in the developing cortex,” says Schneggenburger.
A better understanding of the plasticity of inhibitory interneurons should be beneficial for our understanding of brain diseases like autism spectrum disorders, which are thought to be related to the heightened plasticity during the critical period.
Vickers ED, Clark C, Osypenko D, Fratzl A, Kochubey O, Bettler B, Schneggenburger R;
Parvalbumin-Interneuron Output Synapses Show Spike-Timing-Dependent Plasticity that Contributes to Auditory Map Remodeling.
Neuron 99(4):720-735.e6, Aug 2018. doi: 10.1016/j.neuron.2018.07.018 >