Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican

Synaptic ECM molecules interact directly with receptors and ion channels, modulating their migration and properties.

“Synaptic ECM molecules also interact directly with receptors and ion channels, modulating their migration and properties [34, 35].”

Brevican affects mainly excitatory synapses, regulating both AMPA receptors and potassium channels and the speed and duration of synaptic potentials, leading to impaired hippocampal LTP observed in brevican knockout animals.

“For example, brevican affects mainly excitatory synapses, regulating both AMPA receptors and potassium channels and the speed and duration of synaptic potentials, leading to impaired hippocampal LTP observed in brevican knockout animals [34, 65, 72].”

Brevican regulates the localization of potassium channels and AMPA receptors on PV interneurons, and intact brevican is required for short-term, but not long-term SOR memories.

“Another component of PNNs - brevican - regulates the localization of potassium channels and AMPA receptors on PV interneurons, and intact brevican is required for short-term, but not long-term SOR memories [34] (Fig. 2B).”

Structural modification of perineuronal nets alters synaptic transmission, synapse number, and the ion channel/neurotransmitter receptor composition of synapses.

“the structural modification of PNNs alters synaptic transmission [27], synapse number [28], and the ion channel/neurotransmitter receptor composition of synapses [29]”

Genetic ablation of PNN structural components and consequent loss of neuronal PNN integrity can induce loss of synapses and impaired synaptic colocalization/expression of neurotransmitter receptor subunits, potentially manifesting as deficits in synaptic plasticity.

“This may be due in part to the degradation of the PNNs in which synapses are embedded, as the genetic ablation of one or more PNN structural components and consequent loss of neuronal PNN integrity can induce the loss of synapses [28, 80] and impaired synaptic colocalization/expression of neurotransmitter receptor subunits [29], potentially manifesting as deficits in synaptic plasticity (e.g. LTP)”

Contrasting effects of PNN ablation on certain memory tasks and measures of plasticity suggest this is not the case for all types of memory, but differences may be partly attributable to the PNN ablation method used.

“Although contrasting effects of PNN ablation on certain (specifically object recognition) memory tasks and measures of plasticity suggest this is not the case for all types of memory [21, 29, 87], such differences may also be at least partly attributable to the PNN ablation method utilized (e.g. enzymatic digestion vs genetic deletion of PNN components) which can produce differential effects on”

Brevican controls the location of AMPA and potassium channels and might therefore affect synapse dynamics.

“Brevican for example, which is missing in our mouse model controls the location of AMPA and potassium channels and might therefore affect synapse dynamics71.”

Brevican conditional knockdown in PV-expressing cells demonstrated that changes in the expression of specific lecticans alter synaptic input and firing frequency in PV cells.

“In addition, brevican conditional knockdown in PV-expressing cells demonstrated that changes in the expression of specific lecticans alter synaptic input and firing frequency in PV cells (Favuzzi et al., 2017).”

Brevican, an abundant chondroitin sulfate proteoglycan in perineuronal nets, regulates synaptic connections of PV+ basket cells in response to changes in network activity.

“Recent work has revealed that Brevican, one of the most abundant chondroitin sulfate proteoglycans in perineuronal nets, regulates the synaptic connections of PV+ basket cells in response to changes in network activity (Favuzzi et al., 2017) (Figure 7B).”

Brevican is required for spatial working and short-term memories.

“The observation that Brevican is required for spatial working and short-term memories (Favuzzi et al., 2017) reinforces the view that the dynamic transition of interneurons through different cell states in the adult brain is one of the mechanisms used by neuronal networks to adapt in response to experience.”