Selective Threshold Modulation by Inhibitory Neurons Increases Information Transmission

Article: How Neurons Get Past "No"
Source: Salk Institute, via NEI
Published: June 24, 2021

Information (red line) changes convexity
(dashed vs. solid curves) as a function of threshold

Researchers at the Salk Institute explored modulation of neuronal thresholds via inhibitory neurons, testing their theory with cells in the retina. Although ubiquitous in the brain, threshold modulation also reduces the strength of the original signal, prompting the question as to why such a dampening effect is so widespread. The researchers found that the decrease in information transmission can be nearly completely eliminated if modulation by inhibitory neurons is applied selectively to the most sparsely responding neurons (i.e., neurons with the lowest spike rate) in a circuit or group of neurons. The authors provide a mathematical (but intuitive) explanation for this outcome relating to the curve of the information function of a single neuron with respect to its threshold. As they explain in the paper, "This function is concave for small thresholds and convex for large thresholds. This is important because concave functions decrease their value upon averaging of their inputs, as occurs as a result of threshold modulation, while convex functions increase their value. This means that neurons with small thresholds, i.e., high spike rates, will suffer a decrease in information transmission upon modulation. In contrast, neurons with large thresholds, i.e., small spike rates, will increase information transmission upon threshold modulation." Therefore, neurons with the smallest spike rates will experience the greatest increase in information transmission upon threshold modulation. The researchers tested their predictions on retinal (sustained Off-type) amacrine cells modulating pairs of ganglion cells, termed "adapting" and "sensitizing," with "the main differences between these cell types are that adapting cells have higher thresholds and larger noise levels than sensitizing cells." They found that the amacrine cells exert a stronger effect on the threshold of adapting ganglion cells than on the threshold of sensitizing ganglion cells. The exploratory techniques involve intracellular current injection of the neurons, which is far from clinical applications. Nonetheless, these findings at the cellular level are relevant in providing knowledge in foundational science that could inform later clinical treatments.

My rating of this study: ⭐⭐⭐

Hsu WM, Kastner DB, Baccus SA, et al. "How inhibitory neurons increase information transmission under threshold modulation." Cell Reports.  35(8):109158. 25 May 2021. https://doi.org/10.1016/j.celrep.2021.109158