Excitation Inhibition Balance

Cross references: 
Glutamate    Excitation   GABA   Inhibition     
Lamprey Fast-Slow Twitch          
Sympathetic Nervous System     


08-08-18 

After reviewing the original 1096 references identified in the "excitation inhibition balance" search, I finally narrowed the results down to six High Priority References that are listed at the bottom of this page.  The next step is to look at the Motor Programs  which determine the sequence of excitations and inhibitions which manifest themselves as purposeful behavior.      


08-05-18 

My interest in the  Excitation vs. Inhibition  balance was based on my assumption that it reflected an  active vs. passive balance.    For the most part, it doesn't seem to.  Most of the references I found were concerned with levels of nerve activity rather than levels of observable behavior.  Perhaps I should go back and look specifically for levels of observable behavior. 


Searching PubMed for "excitation inhibition balance" originally located 1093 references but this rose to 1096 references on 7-18-18: 
    NOTE:  These 1096 references were sorted by Publication Date rather than by Link. 
   

1976  1091<1093
    Excitation-mediating and inhibition-mediating dopamine-receptors: a new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data. 
    My comment
        D1R & D2R     

   
1996  1027<1093. 
    "We conclude that lateral connections could produce and maintain a cortical network having dynamic properties without the need to invoke synaptic plasticity. Individual neuron properties could be modified by changing the balance of cortical layer excitation and inhibition."  


1998  999<1093
    "Using dual recordings from excitatory pyramidal neurons and inhibitory fast-spiking neurons in neocortical slices, we report that sustained activation by trains of several hundred presynaptic spikes resulted in much stronger depression of synaptic currents at excitatory synapses than at inhibitory ones"
    My comment
Although the paper doesn't explicitly say so, I think that the stronger depression at excitatory synapses indicates that they are more reactive.   


1999  988<1093
   "The function of cortical circuits depends critically on the balance between excitation and inhibition. This balance reflects not only the relative numbers of excitatory and inhibitory synapses but also their relative strengths. Recent studies of excitatory synapses in visual and somatosensory cortices have emphasized that synaptic strength is not a fixed quantity but is a dynamic variable that reflects recent presynaptic activity."  
    My comment
Synapes.  Not behavior. 


*1999  984<1093

Objective: To examine inhibition in the human motor cortex before and during voluntary movements.

Methods: The balance between the excitation and inhibition of corticospinal neurons in the human motor cortex was tested by conditioning the motor evoked potentials (MEP) evoked in forearm muscles by transcranial magnetic stimulation with a preceding subthreshold stimulus delivered through the same coil.

Results: When normal individuals (n = 9) made a tonic wrist extension, inhibition of the forearm extensor MEP decreased, whereas that of the forearm flexors was unchanged. When these individuals made a tonic wrist flexion, inhibition of the forearm flexor MEP diminished, whereas that of the forearm extensors was unchanged. When normal individuals (n = 10) made a phasic wrist extension in response to an auditory signal, inhibition of the extensor MEP began to decline about 95 msec before the onset of the agonist EMG activity.

Conclusions:    "The changes in balance of excitation and inhibition of corticospinal neurons associated with a voluntary movement precede the movement and are directed at the corticospinal neurons projecting to the agonists. These changes may help to select the population of cortical neurons responsible for the movement."
    My comment:

Come back to this. It could be very important. Behavior
    186 Similar articles:
https://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed&from_uid=10489033



2002  933<1093

   "Cortical excitability reflects a balance between excitation and inhibition. Glutamate is the main excitatory and GABA the main inhibitory neurotransmitter in the mammalian cortex. Changes in glutamate and GABA metabolism may play important roles in the control of cortical excitability. Glutamate is the metabolic precursor of GABA, which can be recycled through the tricarboxylic acid cycle to synthesize glutamate."  
    My comment
Cortical excitability, not behavior. 


2004  899<1093
    "Libet discovered that a substantial duration (> 0.5-1.0s) of direct electrical stimulation of the surface of the somatosensory cortex at threshold currents is required before human subjects can report that a conscious somatosensory experience had occurred."
    My comment:
Consciousness, not behavior.


2004  898<1093

   "In the intact brain, neurons are constantly subjected to both excitatory and inhibitory inputs to their dendritic trees."  
    " Liu's most important finding of a functional nature is that inhibition appears to act quite locally; that is, an inhibitory synapse effectively opposes an excitatory synapse only when it is very close by within the same dendritic branch "  
    My comment
This implies that synapses of opposing polarity can influence the same dendrite.   

  
2006  842<1093
   "This ongoing temporal evolution between excitation and inhibition, which exhibits remarkable proportionality within and across neurons in active local networks, may allow for rapid transitions between relatively stable network states, permitting the "modulation of neuronal responsiveness in a behaviorally relevant manner."  
     My comment
I don't see any reason why the "ongoing temporal evolution" should "modulate neuronal responsiveness". 


2006  840<1093
    My comment
Neurotransmitters and receptors.  Not behavior. 


2006  839<1093
    "The GABA(B) receptor-mediated modulation of glutamatergic excitation in the ICC provides a likely mechanism for preventing overstimulation and/or regulating the balance of excitation and inhibition involved in processing auditory information."  
    My comment
Neurotransmitters and receptors.  Not behavior. 


2006  827<1093
    "Primary cultures of mouse parietal cortex, prepared between postnatal day 3 (P3) and P9, were studied using transmission electron microscopy and HPLC of 
   excitatory (aspartate and glutamate) and  
    inhibitory neurotransmitters (glycine, GABA and taurine) to determine their morphological and functional development."  
    My comment
Parietal cortex cultures.  Not behavior. 


2007  789<1093
    "The findings suggest that recruitment of inhibition and excitation within the sensorimotor cortex correlate. However, inhibitory effects are recruited at lower intensities and saturate earlier than excitation."  
    My comment
Receptors.  Not behavior. 


2007  779<1093
    My comment
Neurons.  Not behavior. 


*2008  769<1093
     " A detailed analysis of the E/I balance during evoked spike activity further shows that the firing strength results from a
    simultaneous decrease of evoked inhibition and  
    increase of excitation."  
My comment:  Not surprising. 


*2008  756<1093
In vitro and in vivo measures of evoked excitatory and inhibitory conductance dynamics in sensory cortices.
    " A detailed analysis of the E/I balance during evoked spike activity further shows that the firing strength results from a  
    simultaneous decrease of evoked inhibition and  
    increase of excitation."  
 My comment:  Same as above. 


2008  745<1093
Retrograde GABA signaling adjusts sound localization by balancing excitation and inhibition in the brainstem.   
    "Central processing of acoustic cues is critically dependent on the balance between excitation and inhibition. This balance is particularly important for auditory neurons in the lateral superior olive, because these compare  
    excitatory inputs from one ear and  
    inhibitory inputs from the other ear
to compute sound source location. "  
    My comment
Neurons.  Not behavior. 



2880  739<1093
    "It is predicted that schizophrenia patients treated with acamprosate-like compounds will not exhibit progressive cortical atrophy associated with the anti-dopaminergic effect of classical antipsychotic exposure."      
    My comment
Neurons.  Not behavior. 


2009  717<1093
   "Since the days of Cajal, the CA1 pyramidal cell has arguably received more attention than any other neuron in the mammalian brain. Hippocampal CA1 pyramidal cells fire spikes with remarkable spatial and temporal precision, giving rise to the hippocampal rate and temporal codes. "      
    My comment
Neurons.  Not behavior. 


2010  687<1093 
    "gamma-Amino butyric acid is an extremely important inhibitory neurotransmitter in the mammalian central nervous system and is essential for the overall balance between neuronal excitation and inhibition. It is well documented that GABA deficiency is associated with several important neurological disorders such as Huntington's chorea, Parkinson's and Alzheimer's disease and other psychiatric disorders, like anxiety, depression, pain, panic, or mania"  
    My comment
"psychiatric disorders"  


2010  685<1093 
    "Recordings of synaptic currents during gamma activity revealed that NMDAR-mediated increases in oscillation frequency correlated with a progressive synchronization of phasic excitation and inhibition in the network. Thus, the balance between tonic excitation and tonic inhibition of interneurons may modulate gamma frequency by shaping interneuronal synchronization."  
    My comment
"synchronization of phasic excitation and inhibition"  


2010  684<1093   
"learning deficits and synaptic plasticity" 


2010  665<1093 
    "We find that, immediately after the onset of hearing, sensory-evoked excitatory and inhibitory responses are equally strong, although inhibition is less stimulus-selective and mismatched with excitation. However, during the third week of postnatal development, excitation and inhibition become highly correlated. Patterned sensory stimulation drives coordinated synaptic changes across receptive fields, rapidly improves excitatory-inhibitory coupling and prevents further exposure-induced modifications. Thus, the pace of cortical synaptic receptive field development is set by progressive, experience-dependent refinement of intracortical inhibition."  
    My comment
"cortical synaptic receptive field development"  


2010 650<1093 
     "Here we report that up-states in BLA principal neurons up-states begin with an excitatory drive that is rapidly (within ∼50 ms) overwhelmed by inhibitory input. This excess of inhibitory drive is short lasting (300-400 ms), after which up-states are maintained by a tight balance between excitation and inhibition. This initial large inhibitory input restricts action potential generation and reduces the firing frequency of these cells. These results indicate that, in contrast to cortical neurons, up-states in BLA neurons show an initial period of strong cortically driven feed-forward inhibition. For the remainder of the up-state, feedback inhibition then acts to balance excitatory input."   
    My comment
Neurons, not behavior. 


2011  646<1093 
     "This paper summarizes recent findings showing that the inhibition-excitation balance controls adult brain plasticity and is at the core of the pathogenesis of neurodevelopmental disorders like autism, Down syndrome, and Rett syndrome."  
    My comment
"neurodevelopmental disorders 


2011  643<1093 
    My comment
Somatosensory cortex, not behavior. 


2011  636<1093    



2011  620<1093 
    "These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms." 
    My comment
Cellular E/I balance. 


2011  619<1093 
    "In this review, we discuss how impairments at different stages in GABAergic development can lead to disease states. We also highlight recent studies which show that modulation of the GABAergic system can successfully reverse cognitive deficits in disease models and suggest that therapeutic strategies targeting the GABAergic system could be effective in treating neurodevelopmental disorders." 
    My comment
GABAergic dysfunction. 


2011  610<1093   
  The ongoing balance of cortical excitation and inhibition during early development.
    My comment
Neurons during development.  Not behavior. 



2011  609<1093   


2011  604<1093   
    My comment
Sensory pathways and memory networks.  Not behavior. 


2012  598<1093 
The biochemical anatomy of cortical inhibitory synapses.
    My comment
Synapses.  Not behavior. 



2012  585<1093 


*2012  579<1093 
     "Approximately one in five neurons is GABAergic in many neocortical areas and species, forming a critical balance between inhibition and excitation in adult circuits. During development,
    cortical GABAergic neurons are generated in ventral telencephalon and migrate up to developing cortex where the  
    excitatory glutamatergic neurons are born."  
My comment
    I should come back to this. 


2012  574<1093 
Altered excitation-inhibition balance in the brain of patients with diabetic neuropathy.
    My comment
Diabetic neuropathy.  Not behavior. 


*2012  567<1093 
A mechanism for value-guided choice based on the excitation-inhibition balance in prefrontal cortex.
    "Although the ventromedial prefrontal cortex (vmPFC) has long been implicated in reward-guided decision making, its exact role in this process has remained an unresolved issue.  
    Here we show that, in accordance with models of decision making, vmPFC concentrations of GABA and glutamate in human volunteers predict both behavioral performance and the dynamics of a neural value comparison signal. These data provide evidence for a neural competition mechanism in vmPFC that supports value-guided choice.   
   Free PMC Article
My comment
    I didn't really understand any of this.   


2012  560<1093 
Selective functional interactions between excitatory and inhibitory cortical neurons and differential contribution to persistent activity of the slow oscillation.

My comment
    I should come back to this. 


07-18-18 

Just to confuse things further, the number of references identified by searching PubMed for "excitation inhibition balance" has risen from 1093 to 1096. 


2012  562<1096 



2013  490<1096 


2013  477<1096  
Activity-dependent adaptations in inhibitory axons.    
    My comment
Neurons.  Not behavior. 


*2013  476<1096 
Dysfunctional astrocytic and synaptic regulation of hypothalamic glutamatergic transmission in a mouse model of early-life adversity: relevance to neurosteroids and programming of the stress response.
    "Adverse early-life experiences, such as poor maternal care, program an abnormal stress response that may involve an altered balance between excitatory and inhibitory signals. Here, we explored how early-life stress (ELS) affects excitatory and inhibitory transmission in corticotrophin-releasing factor (CRF) Corticotropin-releasing hormone (CRH)-expressing dorsal-medial (mpd) neurons of the neonatal mouse hypothalamus.  
    We report that ELS associates with enhanced excitatory glutamatergic transmission that is manifested as an increased frequency of synaptic events and increased extrasynaptic conductance, with the latter associated with dysfunctional astrocytic regulation of glutamate levels."  
  
    The neurosteroid 5α-pregnan-3α-ol-20-one (5α3α-THPROG) is an endogenous, positive modulator of GABAA receptors (GABAARs) that is abundant during brain development and rises rapidly during acute stress, thereby enhancing inhibition to curtail stress-induced activation of the hypothalamic-pituitary-adrenocortical axis. In control mpd neurons, 5α3α-THPROG potently suppressed neuronal discharge, but this action was greatly compromised by prior ELS exposure. This neurosteroid insensitivity did not primarily result from perturbations of GABAergic inhibition, but rather arose functionally from the increased excitatory drive onto mpd neurons. Previous reports indicated that mice (dams) lacking the GABAAR δ subunit (δ(0/0)) exhibit altered maternal behavior. Intriguingly, δ(0/0) offspring showed some hallmarks of abnormal maternal care that were further exacerbated by ELS. Moreover, in common with ELS, mpd neurons of δ(0/0) pups exhibited increased synaptic and extrasynaptic glutamatergic transmission and consequently a blunted neurosteroid suppression of neuronal firing.  

    "This study reveals that increased synaptic and tonic glutamatergic transmission may be a common maladaptation to ELS, leading to enhanced excitation of Corticotropin-releasing hormone (CRH)-releasing neurons, and identifies neurosteroids as putative early regulators of the stress neurocircuitry."  
    My comment
See also:   
    "2013 
Dysfunctional astrocytic and synaptic regulation of hypothalamic glutamatergic transmission in a mouse model of early-life adversity: relevance to neurosteroids and programming of the stress response.
  

    I should come back to this. 


2014  472<1096


2014  414<1096 
    "... excitation/inhibition ratios across cortical pyramidal neurons are equalized by activity-dependent modulations of parvalbumin-neuron mediated feed forward inhibition."  
    My comment
Neurons.  Not behavior. 

NOTE: 

    I'm stopping here for the time being because I feel I already have enough references for this search.  I may come back to these references at some time in the future, but for now, I think I have enough to work on.   



HIGH PRIORITY REFERENCES: 

    I've gone through the references a second or third time and given asterisks to the few I want to look at again.  There are 6 of them.  They are:   

    "The changes in balance of excitation and inhibition of corticospinal neurons associated with a voluntary movement precede the movement and are directed at the corticospinal neurons projecting to the agonists. These changes may help to select the population of cortical neurons responsible for the movement."  
    187 Similar articles
    43 Cited by's




    "Although the ventromedial prefrontal cortex (vmPFC) has long been implicated in reward-guided decision making, its exact role in this process has remained an unresolved issue. Here we show that, in accordance with models of decision making, vmPFC concentrations of GABA and glutamate in human volunteers predict both behavioral performance and the dynamics of a neural value comparison signal. These data provide evidence for a neural competition mechanism in vmPFC that supports value-guided choice."      
        Free PMC Article   
    115 Similar articles
    46 Cited by's
       
    ""This study reveals that increased synaptic and tonic glutamatergic transmission may be a common maladaptation to ELS (Early Life Stress), leading to enhanced excitation of CRF-releasing neurons, and identifies neurosteroids as putative early regulators of the stress neurocircuitry."    Free PMC Article 
    My comment:  This might provide a physiological substrate for later psychological problems.     
    155 Similar articles
    32 Cited by's






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