Talk:Balance of excitation and inhibition

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    We would like to thank the two reviewers for taking the time to go over the article and their helpful suggestions. At this time, we did not yet receive the review of Referee B.

    Response to Reviewer A

    In response to the main comment, we have revised the introductory part of the article to explicitly state that the term ‘excitatory-inhibitory balance’ has different meanings. We tried to describe these distinct meanings by saying that “excitatory and inhibitory inputs of a neuron are said to be balanced if across a range of conditions of interest the ratio between the two inputs is constant”. The exact meaning of the balance depends on the ‘conditions of interest’ (e.g., brief sensory stimuli of varying strength or spontaneous activity measured across seconds or minutes) and on the way the synaptic inputs are measured (as currents, conductances, etc.).

    The section on excitatory-inhibitory sensory selectivity was updated to explicitly state that there is a transient imbalance due to the earlier onset of the excitatory synaptic input.

    Finally, the paragraph on forward suppression, which suggests that inhibition has absolutely no role in the phenomenon, was changed to imply that inhibition is not the primary cause for the suppression.

    Reviewer A comments

    A major suggestion is that the article be revised to highlight that “balance of excitation and inhibition” has several different meanings in the current neurobiological literature.

    The definition currently stated in the abstract “Excitatory and inhibitory inputs of a neuron are said to be balanced if across a range of conditions of interest the ratio between the two inputs is constant.” This definition, from Wehr and Zador (2003) and Shu et al (2003), could apply either to trial-averaged responses (in which, on individual trials, excitation and inhibition may be unbalanced) or hold for single trials, a much more stringent definition of balance (Okun and Lampl 2008). For this definition of balance, the ratio of excitation and inhibition is not important, just that the particular ratio is constant.

    In an alternative definition, it is the magnitude of the ratio between excitation and inhibition that is important. This magnitude is usually defined by averaging across all conditions.  For example, Fagiolini and Hensch (2003) define the magnitude of the ratio between excitation and inhibition with respect to the phenomenon of critical period plasticity. In contrast, van Vreeswijk and Sompolinsky (1996) (also eg. Miller and Troyer, 1997; Renart et al 2003) define the magnitude with respect to the irregular spiking of cerebral cortical neurons.  Renart et al (2003) also note that “voltage-independent” and “conductance based” synaptic current models of irregular spiking only share a loose common definition of balanced excitation and inhibition: “Thus, there is no more ‘balance’ condition to be fulfilled in this situation [conductance-based synaptic currents], unless additional hypothesis are used. In any case, the simple balanced network picture is useful as a metaphor for networks with strong coupling and highly irregular firing of its constituent neurons. We will use the term ‘balanced network’ in this loose sense in the following.”

    It may also be noted that the phenomenon named “balanced inhibition” by Wehr and Zador (2003) has been used to illustrate that “large imbalances can occur transiently during the response to stimuli” (Markram et al 2004).  Both of these descriptions are reasonable given the different definitions of “balanced” used by the respective authors.  

    A very minor debatable point is “Such forward suppression was widely believed to be due to inhibition evoked by the first stimuli. However, intracellular conductance measurements found that the inhibitory synaptic input evoked by the first click ends long before the second click, rendering the above explanation wrong (Wehr and Zador, 2003, 2005).  The debate does not concern Wehr and Zador’s scientific conclusions, but their relation to previous work.  Brosch and Schreiner (1997) determined the mean duration of extracellularly measured forward masking as 143 ms, whereas Wehr and Zador determined the mean duration of intracellularly measured forward masking to exceed 512 ms. Wehr and Zador’s own recordings, and subsequent recordings by Wu et al (2006, 2008) show that intracellularly measured inhibition lasts approximately 100 ms, and contributes to the extracellularly measured forward suppression (Fritz et al, 2005).

    A reference for the cortical response evoked by a single presynaptic thalamic spike is Bruno and Sakmann (2006).

    Additional references not currently in Okun and Lampl’s list:

    Brosch M, Schreiner CE (1997) Time course of forward masking tuning curves in cat primary auditory cortex. J Neurophysiol 77:923-43.

    Fagiolini and Hensch (2003) Excitatory-inhibitory balance controls critical period plasticity.  In Excitatory-Inhibitory Balance, ed. Hensch and Fagiolini, Springer.

    Fritz J, Shamma S, Elhilali M (2005) One click, two clicks: the past shapes the future in auditory cortex.  Neuron 47:325-7.

    Troyer TW, Miller KD (1997) Physiological gain leads to high ISI variability in a simple model of a cortical regular spiking cell.  Neural Comput 9:971-83.

    Renart A, Brunel N and Wang X-J (2003) Mean-field theory of recurrent cortical networks: from irregularly spiking neurons to working memory.  In Computational Neuroscience: A Comprehensive Approach, ed. J. Feng, CRC Press.

    Bruno and Sakmann (2006) Cortex is driven by weak but synchronously active thalamocortical synapses. Science 312(5780): 1622-7

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