Sensory Neurons: Mechano-Afferent Neurons

Introduction

• Until now, we have focused on neurons as isolated entities, or interacting with other neurons.

• But neurons play a crucial role in behavior, which in turn allows animals to survive and reproduce. The only way that neurons can do this is if they allow animals to interact with the outside world - to sense what is happening in the surrounding environment, and to act on what is sensed by moving the animal's body.

• Even very simple micro-organisms, like an Amoeba or a Paramecium, have the ability to sense and respond to their environment; but they do this with a single cell, since that is their entire body.

• In more elaborate multi-cellular organisms, the task of sensing is performed by specialized neurons, sensory neurons.

General Principles of Sensory Systems

• Several general principles characterize sensory systems.

• First, sensory neurons contain receptors that are specialized to recognize particular features in the environment. The features that are recognized are forms of energy:
  • chemical energy,
  • radiant energy,
  • thermal energy, or
  • mechanical energy.

• Receptors for these different forms of energy correspond to specialized sensors that give rise to the senses that are familiar to us:
  • chemoreceptors that can bind and respond to molecules are olfactory or gustatory sensors, the first stage in smelling and tasting, and some specialized receptors for molecules signaling tissue damage, that give rise to pain,
  • photoreceptors that can sense light of different colors, the first stage in vision,
  • thermoreceptors, the first stage in sensing heat or cold, and, in response to extremes of temperature, pain,
  • mechanoreceptors, the first stage in sensing touch, hearing, balance, and the sense of self (proprioception), i.e, the position of parts of the body.

• Second, through appropriate ion channels in the specialized sensors, the different energy sources are transformed into changes in potential across the membrane of a neuron. If sensory information needs to be transmitted over long distances, these receptor potentials give rise to action potentials. Transforming the different forms of energy into the common currency of voltage changes and action potentials is called stimulus transduction. At the molecular level, the process involves changes in ion channels, including those we have encountered before (ligand-gated ion channels that respond to chemicals), as well as some new ion channels (e.g., ion channels that respond to light through a chemical cascade induced by the effects of light on light-sensitive molecules, or ion channels that can be gated by mechanical forces, such as stretch-sensitive ion channels). The amplitude and duration of the receptor potential, and the corresponding pattern of neural firing, are proportional to the environmental energy transduced by the receptors.

• Third, each class of sensors has many sub-modalities. Taste sensors in the human tongue can sense sweet, sour, bitter or salty features of a food; in the human eye, different photoreceptors are maximally sensitive to blue, green or red light; mechanoreceptors are sensitive to different frequencies of vibration. The pattern of activity in receptors that are tuned to different components of the energy impinging on the body give rise to particular sensory perceptions.

• Fourth, the receptors and sensory neurons may transform the sensory input through adaptation. Slowly adapting receptors remain active as long as a stimulus is present, though their activity may decline. Rapidly adapting sensors respond primarily to changes - when the stimulus is first encountered, they are strongly activated, and when the stimulus is removed, they are strongly activated. But they rapidly cease to respond if the stimulus remains unchanged for any prolonged period of time.

• Fifth, many senses are organized spatially. For example, the ability to localize touch to different parts of the body, to identify the location of objects in the visual field, or the location of a sound, are all related to the spatial encoding of sensory inputs.

• Sixth, the specificity of senses are maintained by the locations to which the neuron carrying sensory information project within the brain. Thus, if one electrically stimulates neurons that carry visual stimuli, the activity of these neurons will be sensed as light or more complex visual percepts, whereas if neurons that carry touch sensations are electrically stimulated, the result will be sensed as touch or more complex mechanical stimuli, even though the electrical stimulation is simply inducing additional action potentials in both sets of neurons.

• Seventh, sensing is an active process, in three very important ways. The first aspect of active sensing is that we generally obtain sensory inputs during behavior, and the process of sensing is continually altered by behavior. Thus, to look at an object, we often move our eyes, our head, and sometimes our entire body. Similarly, to understand the properties of an object, we often pick it up, turn it around, thus scanning it with the most precise part of our visual system (the fovea, the part of the retina that has the densest concentration of photoreceptors sensitive to fine visual detail), and combining this with the most sensitive parts of our mechanical sensing system (the tips of our fingers, which have the densest concentration of mechanoreceptors). As this example illustrates, active sensing also involves integrating multiple sensory modalities (here, vision and touch). The second aspect of active sensing is that both within the receptor, and certainly within one or two synapses of the original input, the sensory information may be transformed. Thus, for example, inhibitory inputs in regions surrounding the primary sensory inputs may act to sharpen the inputs, enhancing their specificity and their contrast with surrounding features. The third aspect of active sensing is that parts of the nervous system that are more central provide extensive feedback to primary sensory inputs, shaping them, so that certain features of the input may be enhanced or eliminated entirely. It is important to recognize that sensing is not a precise record of what has occurred in the environment, but an extraction of the most salient features that are needed for behavior.

• Eighth, what we sense and how we sense it is also a product of experience. We can learn to make much finer distinctions among colors (think of the many colors that a fashion designer can describe), tastes and smells (think of the many different tastes that a food or wine critic, or a perfumer, can learn to distinguish), or sounds (think of the auditory acuity that develops in someone who is blind, allowing them to sense surfaces, obstacles and oncoming objects through sound alone). A striking example of plasticity is the ability of babies to produce and respond to all the phonemes that are present in all languages initially, but then to lose the sensitivity to all but those phonemes that are characteristic of the language of the adults that are raising them after about a year. All of the mechanisms of plasticity that you learned about in earlier units allow us to shape our sensory inputs.

The Sense of Touch and Mechanoafferents

• In this unit, we will focus on one sense: the sense of touch, which is transduced by mechanoafferents.

• When we grip and lift an object, we need to rapidly deduce many features about it if we are to be successful in completing this apparently simple action. How smooth are the object's edges, and how likely is it to slip from our grasp? How heavy is it, and thus how much force do we need to exert to lift it? How fragile is it, and thus what limits do we need to place on our grip force to keep it from crumbling or shattering as we lift it? How solid is it, and will we need to compensate in some way if it begins to sag or flow away?

• In the hand, there are four key mechanoreceptors: the Merkel cell, the Meissner corpuscle, Ruffini endings, and the Pacinian corpuscle. All play complementary roles during manipulation.

• The Meissner corpuscle is found very close to the skin surface. It is best stimulated by movements along the surface of the skin. The Meissner corpuscle connects to the rest of the nervous system via an axon referred to as a rapidly adapting fiber (RA type 1 or RA1 fiber), it has its peak frequency response at 50 Hz (cycles per second), and it can respond to indentations on the order of 2 micrometers. These fibers can respond to the rate at which force is applied, as well as movements of the hand relative to the object that is being gripped.

• The Pacinian corpuscle is found in much deeper tissue, and is exquisitely sensitive to vibration; its best frequency range is 200 Hz, and it can respond to indentations on the order of a hundredth of a micrometer. Each Pacinian corpuscle is connected to the rest of the nervous system via a single rapidly adapting fiber (RA type 2 or RA2). As an object is grasped, these sensors can respond to vibrations that occur when the hand contacts the object, when the object lifts off a surface, when the object contacts another surface, and when the hand releases its grasp of the object.

• The Merkel cell is found at the tips of the epidermal ridges. It is most sensitive to edges and points of objects, responds most strongly to frequencies at about 5 Hz, and responds to indentations of about eight micrometers. Multiple Merkel cells are connected to the rest of the nervous system via axons referred to as slowly adapting fibers (slowly adapting type 1, or SA1 fibers). These play a crucial role in monitoring grip force.

• The Ruffini endings are in the dermis, and are primarily sensitive to skin stretch. Each is connected to the rest of the nervous system via an axon referred to as a single slowly adapting fiber (slowly adapting type 2 or SA2 fiber). These endings are most sensitive to larger indentations of the skin (about 40 micrometers). During grip, they encode the posture of the hand.

• A recent review of mechanotransducers and their underlying ion channels can be found here.

• The simulation is based on a model of how force is transformed into current (so that the sensitivity of a mechanoafferent neuron has units of picoCoulombs/milliNewton); the model can be found here.

Analyzing the Properties of Mechanoreceptors

• You now have enough information to begin to analyze mechanoreceptors. Below you will find a simulation that allows you to explore the properties of two types of mechanoreceptor: Meissner corpuscles and Merkel cells. Please open the simulation.

• Question 1: We will start by examining the properties of the Meissner corpuscle. Press the Meissner Corpuscle Simulation button.
  • (a) What do you observe about the membrane potential of the Meissner corpuscle? How many action potentials do you observe and when do they occur? Please measure the time it takes for the touch to rise from 0 mN to the maximum value and how long it takes to fall from the maximum value to 0 mN.
  • (b) Now, under Touch Stimulus Properties, set the Applied pressure time constant and Removed pressure time constant to 20 ms and run the simulation. What do you observe about the cell’s response to the touch stimulus? How many action potentials do you observe? Again measure the time it takes for the touch to rise from 0 mN to the maximum value and how long it takes to fall from the maximum value to 0 mN.
  • What do parts (a) and (b) imply about how the Meissner corpuscle responds to rapidly and slowly changing stimuli? Please explain.

• Question 2: Press the Meissner Corpuscle Simulation button to reset the simulation. Under Touch Stimulus Properties, set the Applied and Removed pressure time constants to 40 ms. Does the cell respond?

• Question 3: Based on your observations in questions 1 and 2, what can you conclude about the behavior of Meissner corpuscles? To what types of touch stimuli do they respond?

• Question 4: Now, let’s examine the behavior of Merkel cells. Start by pressing the Merkel Cell Simulation button. Under Touch Stimulus Properties, set the Maximum pressure to 6 mN and the Applied and Removed pressure time constants to 40 ms. Run the simulation. How does the cell respond? How many action potentials do you observe?
  • Now, under Touch Stimulus Properties, set the Maximum Pressure to 3 mN. Run the simulation. How many action potentials do you observe?
  • Now, under Touch Stimulus Properties, set the Maximum pressure to 8 mN. Run the simulation. How many action potentials do you observe?

• Question 5: Push the Merkel Cell Simulation button to restore the default parameters. Under Touch Stimulus Properties, set the Maximum pressure to 3 mN and the Applied and Removed pressure time constants to 40 ms. Run the simulation. What do you observe?
  • Now set the Applied and Removed pressure time constants back to 4 ms. What do you observe about the cell's response? How many action potentials do you observe and when do they occur? Some sensory neurons respond only to changes in stimuli whereas other sensory neurons have a stimulus threshold that must be reached before they will respond. Do you think all sensory neurons respond in only one of these ways, or could they have multiple modes of response? Please explain how these ideas are relevant to what you are observing.

• Question 6: Based on your observations in questions 4 and 5, how does a Merkel cell respond to touch stimuli? Which factors affect its firing rate?

• Question 7: Now press the Both Mechanoreceptors button to get a display for comparing the responses of the two cells to the same sets of stimuli. Note that you can now observe each cell's current.
  • To test your understanding of properties you have examined thus far, can you create a set of stimuli that the Meissner corpuscle responds to strongly, but the Merkel cell does not? Your Merkel cell can still have a response, but it should be much weaker than that exhibited by the Meissner corpuscle. To be more specific, the stimulus should induce the Meissner to fire many action potentials, whereas it should only induce a few action potentials in the Merkel cell. What kind of stimulus did you use and why?
  • Press the Both Mechanoreceptors button to reset the simulation. This time, design a set of stimuli to which the Merkel cell responds much more strongly than the Meissner corpuscle. To be specific, the Merkel cell should fire strongly throughout the stimulus, whereas the Meissner corpuscle should show few or no action potentials. What type of stimuli did you use and why?

• Question 8: A free nerve ending is a type of mechanoreceptor that responds specifically to painful stimuli, including those of a much greater force than the mechanoreceptors we have been examining. Reset the simulation by pressing the Nociceptor button. Increase the Maximum pressure under First Touch Stimulus to 15 mN. How does the nerve cell respond? For the purposes of this question, you can assume that 15 mN is a painful stimulus.
  • Under the Nociceptor Cell Current Properties, you will see three variables: Sensitivity to steady force, Sensitivity to force increase, and Sensitivity to force decrease. These, respectively, control how much the mechanoreceptor responds to the amount of force being applied, how much the force is increasing, and how much the force is decreasing. By altering these properties, can you create a type of mechanoreceptor that responds to painful stimuli (defined as a pressure of 15 mN) with high frequency action potentials throughout the stimulus? What settings did you use and why?