Spatiotemporal dynamics in a network composed of neurons with different excitabilities and excitatory coupling

Spiral waves have been observed in the biological experiments on rat cortex perfused with drugs which can block inhibitory synapse and switch neuron excitability from type II to type I. To simulate the spiral waves observed in the experiment, the spatiotemporal patterns are investigated in a network composed of neurons with type I and II excitabilities and excitatory coupling. Spiral waves emerge when the percentage(p) of neurons with type I excitability in the network is at middle levels, which is dependent on the coupling strength. Compared with other spatial patterns which appear at different p values, spiral waves exhibit optimal spatial correlation at a certain spatial frequency, implying the occurrence of spatial coherence resonance-like phenomenon. Some dynamical characteristics of the network such as mean firing frequency and synchronous degree can be well interpreted with distinct properties between type I excitability and type II excitability. The results not only identify dynamics of spiral waves in neuronal networks composed of neurons with different excitabilities, but also are helpful to understanding the emergence of spiral waves observed in the biological experiment.

Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease

Background Alzheimer’s disease(AD)is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists.Neuroinflammation is central to the pathology progression,with evidence suggesting that microglia-released galectin-3(gal3)plays a pivotal role by amplifying neuroinflammation in AD.However,the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains unknown.Methods Here,we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo(20-80 Hz)by performing electrophysiological recordings in the hippocampal CA3 area of wild-type(WT)mice and of the 5×FAD mouse model of AD.In addition,the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes,and amyloid-β(Aβ)plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout(KO).Results Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner,which was accompanied by impairment of cellular dynamics in fast-spiking interneurons(FSNs)and pyramidal cells.We found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139,which also prevented Aβ42-induced degradation of gamma oscillations.Further-more,the 5×FAD mice lacking gal3(5×FAD-Gal3KO)exhibited WT-like gamma network dynamics and decreased Aβplaque load.Conclusions We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs,inducing a network performance collapse.Moreover,our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.