Research on sensory adaptation has brought to light a previously overlooked organizing principle of physiology

Research on sensory adaptation led by University of Toronto Engineering professor Willy Wong may have unearthed a previously overlooked organizational principle of physiology.

Biologists have long known that organisms adapt to a constant stimulus in a similar way, says Wong.

“Imagine you walk into a room someone has just painted. You’ll likely think, ‘This smells bad.’ But the sensation decreases as you stay in there. The molecules don’t disappear, not within that time frame. You’ve just gotten used to it.”

From an initial state, the organism’s response activity rises to a peak response, then falls to a new final steady state. Wong has discovered that those three fixed points on the adaptation curve form a mathematical relationship that is obeyed across all sensory modalities and organisms.

“I compared 250 measurements of adaptation from different branches of sensory physiology and found that they are all compatible with a single, simple equation,” says Wong.

His findings, the first quantitative comparison of adaptation responses, are presented in a paper in Frontiers of Human Neuroscience.

Wong’s recent work in brain-machine interfaces, such as a retinal prosthesis to restore vision for blind patients, builds on his long-standing fascination with the neural code – how neurons process information.

Though today’s understanding of the code remains far from perfect, the more researchers understand how our brains convert signals into perceptions, the better they can design technologies to replace lost functions or enhance existing ones.

The idea of a sensory response curve that drops off over time might seem counterintuitive: Shouldn’t a strong sensation return a consistently strong rate of response? But as long ago as the 1920s, physiologists such as Edgar Adrian were demonstrating why not.

Adrian, whose work would win the 1932 Nobel Prize for Physiology or Medicine, used a frog specimen to trace the adaptation phenomenon to the level of single neurons.

He discovered that neurons use a basic unit of communication, a nerve impulse called an action potential, which fires the same signal strength as long as a threshold is reached.

“Action potentials don’t come in half measures,” says Wong. “Either you get one or you don’t. If you do, the neuron needs some time to recharge before it can fire another. In adaptation, the rate of action potential generation falls gradually to some non-zero steady state.”

Adaptation response occurs in all animals, from vertebrates like mammals to invertebrates like insects, and across all sensory modalities. This includes the five traditional senses of vision, hearing, touch, taste and smell, along with somatosensory functions such as proprioception – the body’s awareness of itself – and electroreception, as found in eels.

One of Wong’s biggest surprises was that his equation holds true for some of the oldest multicellular organisms, such as jellyfish, which have very different sensory systems.

“If you shine a light on them, they either fly to the light or away from it – but only because their photoreceptors are hardwired to their motor output,” he says. “Which raises the question, is this equation universal?

In the future, if we find aliens with exobiology never seen on this planet, could they also be constrained by the same limitations or principles?”

In the physical sciences, universality is determined by replication of results, regardless of when, where, or by what method they are obtained. But this is not always possible in biological experiments, which can pose significant barriers to repetition of measurements.

However, when data from unrelated independent studies – cross different time periods, researchers and methods – converge as evidence, it strengthens the case for the conclusion. This principle, called consilience, is based on the premise that science is unified, bolstering consensus in theories such as evolutionary theory and the big bang theory, among others.

“All this data was there,” says Wong, “I took a curve here, a curve there, compared them – even Adrian’s canonical graphs. All conformed to the same geometric mean relationship. It’s not dependent on the researcher, on what equipment was used, or on the organism. From that perspective, it is universal.”

“This is illuminating work from Professor Wong,” says Professor Deepa Kundur, Chair of Electrical & Computer Engineering at the University of Toronto. “It’s a reminder of just how pervasive electrical and computer engineering is – how researchers are able to contribute to many seemingly far-reaching areas of study.”

The discovery of a new physiological equation doesn’t happen every day, and it’s unlikelier still to come from an engineer. Though Wong had been developing these ideas for years, he credits the pandemic with giving him some time to refocus, as well as fruitful periods of research progress.

“I was on the elliptical,” he says, when asked to pinpoint his “a-ha” moment. “Either reading news or thinking about my work. I think that was the moment.”

To live is to adapt to the world around us. This is a notion so embedded in our way of thinking and our language, that even though we all know it when we see it, it remains difficult to define precisely what adaptation means. On long time scales, species evolve to adapt characteristics that are favorable for survival.

Adapt or die! On shorter time scales, individual organisms adapt behaviorally in response to changes in their environment, as, for example, an animal adapts their scavenging behavior to take advantage of a new food source as the previous one is suddenly no longer available.

On even faster time scales, we are all familiar with our eyes adapting as we move from the bright sunlight to a dark room, or as we become accustomed to the sensation of clothing on our bodies, or as we quickly adapt our gait in response to a new pair of shoes. The binding agent between all of these different phenomena seems to be time – adaptation is a change in function that takes time to develop (be it fast or slow) and time to dissipate.

Although it is certainly the case that these different notions of adaptation at disparate time scales arise from different mechanisms and engage different systems within our bodies, they collectively embody something profound that connects them – the ability of organisms to respond to changes in the environment.

On the time scale relevant for an individual organism, there are still many forms of adaptation, but none perhaps as well studied as rapid sensory adaptation of the nervous system, a ubiquitous property of all sensory pathways that has profound effects both perceptually and neurophysiologically (Figure 1).

From a historical perspective, there is documented evidence of the perceptual effects of rapid sensory adaptation going back several centuries. For example, Aristotle observed in 350 B.C. a phenomenon that later came to be referred to as the visual “waterfall” illusion, with perceived visual motion of stationary objects following a fixed gaze on moving objects for just a few seconds.

Over the last few decades, adaptation paradigms have been implemented in psychophysical studies to more precisely determine the extent to which persistent exposure to a sensory input affects our perception. For example, fundamental properties of the visual pathway include adaptation to visual contrast (Georgeson and Harris, 1984; Greenlee and Heitger, 1988), visual orientation (Blakemore and Campbell, 1969a, 1969b), visual motion (Anstis et al., 1998; Sekuler and Ganz, 1963; Wohlgemuth, 1911), and even complex visual features such as faces (Webster and MacLeod, 2011).

For review of visual adaptation, see (Clifford et al., 2007; Kohn, 2007). Although a very wide range of adaptive phenomena has been observed both psychophysically and neurophysiologically at the single neuron level across different sensory pathways, until now we have not been in a position to pose questions in the context of circuits and networks to ultimately enable us to link these to behavior for a more holistic view on rapid sensory adaptation.

In this Perspective, we revisit this classical issue in sensory neuroscience and consider multiple levels of investigation into rapid sensory adaptation to build from intrinsic adaptive properties of a single neuron to adaptive properties within common circuit motifs (Figure 1).

Specifically, we will ask 1) How do we disambiguate adaptation effects occurring within a single neuron from those inherited presynaptically or generated locally in the context of the highly interconnected and detailed anatomy of our sensory pathways? And 2) how does differential adaptation of neurons by synapse type, cell type, or stimulus tuning develop the adaptive circuit properties observed and is this generalized across circuit motifs?

Here, we seek to open these questions up in the context of the modern tools that are making it possible to dissect the function of complex circuits relevant for behavior, and to pose some questions related to how we as organisms navigate the dynamics of the world in which we live.

reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5076890/

reference link :More information: Willy Wong, Consilience in the Peripheral Sensory Adaptation Response, Frontiers in Human Neuroscience (2021). DOI: 10.3389/fnhum.2021.727551