Model-Predicted Balance Between Neural Excitation and Inhibition Was Maintained Despite of Age-Related Decline in Sensory Evoked Local Field Potential in Rat Barrel Cortex.

Sungmin Kang,Ying Zheng,Yurie Hayashi,Evangelos Delivopoulos,Michael Bruyns-Haylett

doi:10.3389/fnsys.2020.00024

Sungmin Kang, Ying Zheng + Show 3 more

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https://doi.org/10.3389/fnsys.2020.00024

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Abstract

The balance between neural excitation and inhibition has been shown to be crucial for normal brain function. However, it is unclear whether this balance is maintained through healthy aging. This study investigated the effect of aging on the temporal dynamics of the somatosensory evoked local field potential (LFP) in rats and tested the hypothesis that excitatory and inhibitory post-synaptic activities remain balanced during the aging process. The LFP signal was obtained from the barrel cortex of three different age groups of anesthetized rats (pre-adolescence: 4–6 weeks, young adult: 2–3 months, middle-aged adult: 10–20 months) under whisker pad stimulation. To confirm our previous finding that the initial segment of the evoked LFP was solely associated with excitatory post-synaptic activity, we micro-injected gabazine into the barrel cortex to block inhibition while LFP was collected continuously under the same stimulus condition. As expected, the initial slope of the evoked LFP in the granular layer was unaffected by gabazine injection. We subsequently estimated the excitatory and inhibitory post-synaptic activities through a balanced model of the LFP with delayed inhibition as an explicit constraint, and calculated the amplitude ratio of inhibition to excitation. We found an age-dependent slowing of the temporal dynamics in the somatosensory-evoked post-synaptic activity, as well as a significant age-related decrease in the amplitude of the excitatory component and a decreasing trend in the amplitude of the inhibitory component. Furthermore, the delay of inhibition with respect to excitation was significantly increased with age, but the amplitude ratio was maintained. Our findings suggest that aging reduces the amplitude of neural responses, but the balance between sensory evoked excitatory and inhibitory post-synaptic activities is maintained to support normal brain function during healthy aging. Further whole cell patch clamp experiments will be needed to confirm or refute these findings by measuring sensory evoked synaptic excitatory and inhibitory activities in vivo during the normal aging process.

Highlights

Sensory evoked cortical field potentials have been shown to change during healthy aging (Onofrj et al, 2001; Wong, 2002)
The objectives of the current study were (i) to investigate the effect of healthy aging on the temporal dynamics of somatosensory evoked local field potential (LFP) in the rat barrel cortex; (ii) to further demonstrate that the initial segment of the evoked LFP solely reflected synaptic excitation for all age groups, and (iii) to estimate the excitatory and the inhibitory neural activities from LFP responses using the balanced model of the LFP, and to compare their ratio across age groups to assess the balance of neural excitation and inhibition during the aging process
Posthoc comparisons using the Bonferroni correction indicated that mean respiration as well as heart rates in the PA group were significantly higher than those in the young adult (YA) and the middle-aged adult (MA) groups, but no significant difference in these parameters was found between the YA and the MA groups

Summary

Introduction

Sensory evoked cortical field potentials have been shown to change during healthy aging (Onofrj et al, 2001; Wong, 2002). At the level of single neurons, these currents have been shown to co-vary, i.e., stronger or weaker excitation is accompanied by stronger or weaker inhibition, with inhibition lagging excitation by a few milliseconds (Wehr and Zador, 2003; Zhang et al, 2003; Higley and Contreras, 2006; Okun and Lampl, 2008; Atallah and Scanziani, 2009; Dehghani et al, 2016) This temporal delay of inhibition provides a brief time interval during which the membrane potential of a neuron depolarizes above the threshold for action potential firing. This principle of co-tuning is referred to as the balance between neural excitation and inhibition

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