Neurophysiology and Regulation of the Balance Between Excitation and Inhibition in Neocortical Circuits

Abstract

Brain function relies on the ability of neural networks to maintain stable levels of activity, while experiences sculpt them. In neocortex, the balance between activity and stability relies on the co-regulation of excitatory and inhibitory inputs onto principal neurons. Shifts of excitation or inhibition result in altered excitability impaired processing of incoming information. In many neurodevelopmental and neuropsychiatric disorders, the excitability of local circuits is altered, suggesting that their pathophysiology may involve shifts in synaptic excitation, inhibition or both. Most studies focused on identifying the cellular and molecular mechanisms controlling network excitability to assess whether may be altered in animal models of disease. The impact of changes in excitation/inhibition (E/I) balance on local circuit and network computations is not clear. Here we report findings on the integration of excitatory and inhibitory inputs in healthy cortical circuits and discuss how shifts in E/I balance may relate to pathological phenotypes.

Nucleus accumbens neurochemistry in human anxiety: A 7 T1H-MRS study

“…Although previous 1 H-MRS studies in humans have supported opposite associations for glutamate and GABA with anxiety (Ende, 2015), our study did not identify significant associations between anxiety and glutamate, GABA or E/I balance. E/I imbalance is a key biomarker of neuropsychiatric disorders (Tatti et al, 2017). Given the strong comorbidity of stress with neuropsychiatric disorders (Peters et al, 2017;Sandi and Richter-Levin, 2009), our study suggests that self-perceived acute stress might be an important contributing factor on the E/I imbalances observed in neuropsychiatric disorders.…”

Chronic chemogenetic activation of forebrain excitatory neurons in postnatal life evokes long-lasting changes in mood-related behavior

“…In this regard, both the MS and PNFLx models have critical periods spanning from P2-14 and P2-11 respectively 74,76,77 . These temporal windows overlap with distinct critical periods including the stress hyporesponsive period 107-109 , a neurodevelopmental window for the refinement of multiple cortical circuits 1,2 , including the maturation of serotonergic afferents to the cortex 110,111 , and the tuning of excitation-inhibition balance across cortical microcircuits 34,112,113 . A recent report indicates that hM3Dq DREADD activation of the medial prefrontal cortex during postnatal life can abrogate the influence of maternal separation on oligodendrogenesis and despair-like behavior 83 .…”

Sensory Processing Sensitivity in the Context of Environmental Sensitivity: A Critical Review and Development of Research Agenda

“…Brain activity responses as measured by fMRI reflect a summation of complex synaptic signalling events. Since information integration is dependent on the co-regulation of glutamatergic excitatory and GABAergic inhibitory inputs onto excitatory principal neurons (Tatti, Haley, Swanson, Tselha, & Maffei, 2017), the excitation-inhibition balance in the brain may well be the basis of the neural mechanisms driving increased sensitivity to environments. Using 5-HTT knockout rats as an animal model for Environmental Sensitivity, approximating high SPS (Homberg et al, 2016), it was found that faster sensory processing was associated with reduced inhibitory control over excitatory principal neurons in the somatosensory cortex, leading to increased excitability and sensory gating (Miceli et al, 2017).…”