Sensory Systems

The nematode Caenorhabditis elegans is among the most intensely studied animals in modern experimental biology. Its amenability to classical and molecular genetics, compact nervous system, and transparency to optogenetic recording and manipulation have led to its being widely used to investigate how individual gene products act in the context of neuronal circuits to generate behavior. C. elegans was the first animal neuronal connectome to be characterized at the level of individual neurons and synapses, and the wiring organization shows significant parallels with the micro- and macro-level structures of more complex brains. It uses a wide array of sensory cues (mechanical, gustatory, olfactory, and thermal), with impressive precision, to determine an appropriate behavioral response, in the form of changes in locomotion and other motor outputs. The small number of neurons (302) and their highly stereotyped morphology have enabled the interrogation of the precise function of individual neurons, in terms of both the genes that they express and the behaviors in which they function. Approximately one third are sensory neurons, located around the mouth and in the tail, as well as along the length of the body. A complex network of interneurons connects these to the motor neurons, the majority of which output to the body wall muscles, arranged along the body, determining the changes in direction and speed of locomotion required for behaviors such as taxiing up gradients of food-related cues or avoiding noxious cues. The ability to combine information about the precise function of individual neurons with circuit knowledge, genetics, and optogenetic approaches has been critical in advancing the molecular and circuit-level understanding of the mechanisms underlying C. elegans’s behavior. In common with that of other animals, C. elegans’s behavior is subject to change in response to prior experience, and this same complement of experimental approaches has provided significant insight into how plasticity and changes in behavioral states are achieved.

Chronic pain lasting months or longer is very common, poorly treated, and sometimes devastating. Nociceptors are sensory neurons that usually are silent unless activated by tissue damage or inflammation. In humans their peripheral activation evokes conscious pain, and their spontaneous activity is highly correlated with spontaneous pain. Persistently hyperactive nociceptors mediate increased responses to normally painful stimuli (hyperalgesia) in chronic conditions and promote the sensitization of central pain pathways that allows low-threshold mechanoreceptors to elicit painful responses to innocuous stimuli (allodynia). Investigations of rodent models of neuropathic pain and hyperalgesic priming have revealed many alterations in nociceptors and associated cells that are implicated in the development and maintenance of chronic pain. These include chronic nociceptor hyperexcitability and spontaneous activity, sprouting, synaptic plasticity, changes in intracellular signaling, and modified responses to opioids, along with alterations in the expression and translation of thousands of genes in nociceptors and closely linked cells.

Synaptic connections in the brain can change their strength in response to patterned activity. This ability of synapses is defined as synaptic plasticity. Long lasting forms of synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), are thought to mediate the storage of information about stimuli or features of stimuli in a neural circuit. Since its discovery in the early 1970s, synaptic plasticity became a central subject of neuroscience, and many studies centered on understanding its mechanisms, as well as its functional implications.

To survive, animals must properly sense their surrounding environment. The types of sensation that allow for detecting these changes can be categorized as tactile, thermal, aural, or olfactory. Olfaction is one of the most primitive senses, involving the detection of environmental chemical cues. Organisms must sense and discriminate between abiotic and biogenic cues, necessitating a system that can react and respond to changes quickly. The nematode, Caenorhabditis elegans, offers a unique set of tools for studying the biology of olfactory sensation. The olfactory system in C. elegans is comprised of 14 pairs of amphid neurons in the head and two pairs of phasmid neurons in the tail. The male nervous system contains an additional 89 neurons, many of which are exposed to the environment and contribute to olfaction. The cues sensed by these olfactory neurons initiate a multitude of responses, ranging from developmental changes to behavioral responses. Environmental cues might initiate entry into or exit from a long-lived alternative larval developmental stage (dauer), or pheromonal stimuli may attract sexually mature mates, or repel conspecifics in crowded environments. C. elegans are also capable of sensing abiotic stimuli, exhibiting attraction and repulsion to diverse classes of chemicals. Unlike canonical mammalian olfactory neurons, C. elegans chemosensory neurons express more than one receptor per cell. This enables detection of hundreds of chemical structures and concentrations by a chemosensory nervous system with few cells. However, each neuron detects certain classes of olfactory cues, and, combined with their synaptic pathways, elicit similar responses (i.e., aversive behaviors). The functional architecture of this chemosensory system is capable of supporting the development and behavior of nematodes in a manner efficient enough to allow for the genus to have a cosmopolitan distribution.