Perineuronal nets control visual input via thalamic recruitment of cortical PV interneurons

In the neocortex, critical periods (CPs) of plasticity are closed following the accumulation of perineuronal nets (PNNs) around parvalbumin (PV)-positive inhibitory interneurons. However, how PNNs tune cortical function and plasticity is unknown. We found that PNNs modulated the gain of visual responses and γ-oscillations in the adult mouse visual cortex in vivo, consistent with increased interneuron function. Removal of PNNs in adult V1 did not affect GABAergic neurotransmission from PV cells, nor neuronal excitability in layer 4. Importantly, PNN degradation coupled to sensory input potentiated glutamatergic thalamic synapses selectively onto PV cells. In the absence of PNNs, increased thalamic PV-cell recruitment modulated feed-forward inhibition differently on PV cells and pyramidal neurons. These effects depended on visual input, as they were strongly attenuated by monocular deprivation in PNN-depleted adult mice. Thus, PNNs control visual processing and plasticity by selectively setting the strength of thalamic recruitment of PV cells.

eLife digest Our brains continue to develop after we are born. As sights, sounds and smells flood our senses, networks of neurons go through periods of rapid rewiring. Known as ‘postnatal critical periods’, the brain uses these periods to adapt to the signals supplied by our senses. For example, a postnatal critical period exists where infants develop the ability to process what they can see. If their vision is blocked until after the end of the critical period, they may not ever fully gain normal vision. In the outer layer of the brain, known as the cortex, neurons called parvalbumin basket cells appear to help to regulate critical periods. The basket cells synchronize the activity of groups of neurons, creating rhythmic patterns of neural impulses. In the visual cortex these patterns are the brain's way of representing incoming information from the eyes. When a critical period ends, dense nets of protein and sugar start to form around the basket cells in the neural circuit. Dissolving the nets in adult animals re-activates the ability of the circuit to rewire its connections. How the nets limit this rewiring in the first place was not known. Faini et al. have now investigated the role of the nets on the visual cortex of adult mice. Monitoring the activity of neurons revealed that the nets around basket cells ‘muffle’ an important circuit that forms part of the visual pathway. The nets reduce the strength of incoming signals from the eyes before they reach the basket cells. Disrupting the nets allows the visual signals to get through and enables the connections between neurons to respond in a similar way to their behaviour during the postnatal critical period. However, these changes in neural activity were much reduced in mice that had been prevented from seeing out of one eye. This emphasizes the importance of sensory input for rewiring neural circuits. Faini et al. propose that the build-up of nets helps to protect basket cells in the visual cortex from being over-activated by sensory circuits. But this comes at the cost of reducing the ability of the neurons to form new connections, hence making learning and acquiring new skills more difficult. The brains of individuals with psychiatric conditions such as schizophrenia and some forms of autism show disrupted nets around basket cells. Investigating the roles of these nets in more detail could therefore help researchers to develop new treatments for such conditions. More widely, understanding precisely how cortical circuits lose their ability to rewire themselves improves our knowledge of how we learn and store memories.