Cytokines, synaptic plasticity and network dynamics: a matter of balance

Abstract

The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized. However, the specific mechanisms underlying this fine crosstalk have yet to be fully disentangled. To control cognitive function and behavior, the two systems are engaged in a subtle interacting act. In this scenario, a dual action of pro-inflammatory cytokines in the modulation of brain network connections is emerging. Pro-inflammatory cytokines are indeed required to express physiological plasticity in the hippocampal network while being detrimental when over-expressed during uncontrolled inflammatory processes. In this dynamic equilibrium, synaptic functioning and the performance of neural networks are ensured by maintaining an appropriate balance between pro- and anti-inflammatory molecules in the central nervous system microenvironment.

Keywords: brain networks; cognition; cytokines; hippocampus; memory; neuroimmunology; neuroinflammation; synaptic plasticity.

Figure 1

Functional brain network disconnection during inflammatory processes. Under homeostatic conditions, the balance between pro-inflammatory and anti-inflammatory mediators could contribute to the normal expression of activity-dependent synaptic plasticity and homeostatic synaptic scaling, participating in integrative and associative activities in neuronal networks (left panel). During acute inflammatory insults, increased production of pro-inflammatory mediators from IS cells affects functional synaptic properties, perturbating the ability to express plastic changes and subsequently disrupting neuronal network activity (middle panel). With the resolution of the acute inflammatory response, synapses recover their plastic properties, enabling neuronal networks to re-consolidate (right panel). Created using GIMP 2.10.28. IFN-γ: Interferon γ; IL-10: interleukin-10; IL-17: interleukin-17; IL-1β: interleukin-1β; IL-4: interleukin-4.