The Tiniest Brain Is Not Simple

The nematode worm Caenorhabditis elegans has the smallest brain in a free-living animal. There are two forms of C. elegans, male and hermaphrodite. The hermaphrodite brain contains only 302 neurons and the male 385 neurons. The physical characteristics and brain design are different, but there is much in common. The entire body contains approximately 900 cells and is only one millimeter long. Because of its small size, scientists have conducted a significant amount of research on the brain, in the hope of discovering how brains in general function. A few years ago, researchers were able to determine the entire map of the brain, called a connectome, and published the results in the journal Nature.¹ C. elegans is the first animal where this was accomplished.

Even a cursory examination of the connectome shows the complexity of the brain, despite its tiny size. Additional complexity is exhibited by the diversity of the types of neurons and the variety of connections. There are three basic types of neurons — sensory neurons, motor neurons, and interneurons. Sensory neurons respond to various stimuli (chemical, physical, etc.). Motor neurons connect to muscles to control movement. Interneurons are generally intermediate between sensory and motor neurons. 

C. elegans Behaviors

C. elegans exhibits a number of behaviors, some that are complex. That is surprising considering it is a simple organism with such a small brain. The basic behaviors include feeding, fasting, mating, egg laying, and several forms of movement. These include swimming when in liquid media and “crawling” on solid surfaces. They also exhibit a non-movement behavior called quiescence. Research has found that the behaviors are controlled by various neural networks as well as being regulated by neurotransmitters such as serotonin and dopamine and neuropeptide signaling.² These forms of neural signaling exist in all animal brains. The conclusion of the same research regarding these behaviors is that, “Episodic regulation of C. elegans behavior is complex because episode incidence and timing are regulated by the interplay between multiple circuit systems.”

In addition to basic behaviors, C. elegans is also capable of learning, including associative and non-associative learning. A paper published in the Journal of Neurochemistry documented the learning behaviors, including attraction and aversion to salt, temperature, and other substances.³ What might be surprising to many is that this learning involves both short-term and long-term memory mechanisms, which include regulation of neurotransmitters. The conclusion of the same paper was the expectation that the findings “Will provide critical insights in the context of learning and memory disorders in higher organisms, including humans.”

General Characteristics of the Brain

A recent study led by scientists at Hebrew University analyzed the structure of neural networks in C. elegans. One of the findings is that, “The positions of the chemical synapses along the neurites are not randomly distributed nor can they be explained by anatomical constraints. Instead, synapses tend to form clusters, an organization that supports local compartmentalized computations.”⁴ On the other hand the study shows that, “The vast majority of the 302 neurons in C. elegans nematodes lack elaborate tree-like structures. In fact, many of these neurons consist of a single (unipolar) neurite extension, on which input and output synaptic sites are intermittently positioned.” That contrasts with larger brains of advanced animals which do have complex neuron structures. There is a total of 83 sensory neurons and 108 motor neurons. There are approximately 100 classes of neurons that have been identified. There are approximately 5,000 chemical synapses and 1,500-1,700 electrical synapses (gap) junctions.

In the paper that describes the connectome, some of the complexity is summarized as follows, “The major motor neurons as well as their primary pre-motor interneurons are highly interconnected and receive some input from most of the remaining neurons, defying simple interpretation of motor output. The complex circuitry must underlie both the many known behaviours in C. elegans, and the underpinnings for less well understood or novel behaviours, such as learning and memory, inter-animal communication, social behaviour and the complexities of mating.”⁵ Another important finding concerning the connectome is, “The notable similarity in the placement of the nodes to the neuroanatomy of the worm reflects economical wiring, a property commonly found for nervous systems, including in C. elegans.” 

Examination of Neuron Triplets

One notable aspect of the neural networks is that there are a number of triplets, meaning a cluster of three neurons. The paper by the Hebrew University scientists observes, “The clustered organization of synapses is found predominantly in specific types of tri-neuron circuits, further underscoring the high prevalence for evolved, rather than for random, synaptic organization that may fulfill functional role.” One simple instance of a three-neuron cluster is a “feed forward” loop. For example, neuron A is a sensory neuron, neuron B is an interneuron, and neuron C is a motor neuron. Feed forward networks are common in both biological and artificial neural networks. The significance of this is likely that, “The ubiquitous appearance of these circuits in biological networks suggests that they may carry key computational roles, including noise filtering and coincidence detection.” Other research has found that the number of feed forward connections increases as the worm matures.⁶

Additional detailed examination of three neuron clusters found that, “For three different layouts, where each of the three neurons can be either sensory, inter, or motor neuron, there are 63 possible circuit combinations. Of these 63 combinations, few circuits emerged as forming clustered synaptic connections, significantly more than randomly expected.”⁷ The two combinations that are the most common are: (1) two sensory neurons form a postsynaptic contact with an interneuron; and, (2) an interneuron that is presynaptic with two motor neurons. The researchers theorize that combination (1) may function as a signal integrator, and combination (2) may function by synchronizing activation. It seems logical that these would be common circuits as these two functions are likely common in controlling animal behavior.

The Touch Response Neural Network

An interesting example of one neural network in C. elegans that has been elucidated is the “tap withdrawal circuit,” also called the touch response, which controls how the worm responds to being physically touched. The behavior is interesting for a number of reasons, one being that the response exhibits habituation. The neural network is illustrated in Figure 2 here. The network consists of four sensory neurons (red triangles), five interneurons (circles), and two motor neurons (blue triangles). There is a total of seven excitatory chemical synapses (green lines with arrows) and 15 inhibitory chemical synapses (red lines with circles). There are also six electrical (gap junction) synapses (blue lines with squares). The response is activated when the sensory neurons detect a tap. The stimulus is then transferred via the interneurons (PVC and AVD), which then pass it to the command neurons (AVA and AVB). The two output states are either “move forward” (FWD motor neuron) or “move in reverse” (REV motor neuron). The response is modulated through competition between the two command neurons. The competition between commands for moving forward or reverse is evident based on the number of inhibitory synapses. It is obvious that even for such a simple behavior the neural circuit is relatively complex.

Tiny But Not Simple

There are several observations that can be drawn from research into the brain of C. elegans. One is that even though the brain is tiny, it does not have a simple structure. One might expect the smallest known brain to have a structure that is either relatively uniform or random. An example of a uniform structure is that found in crystals, which form a symmetrical lattice. A random structure would be expected if the positions of the neurons were not specified, but rather develop through a random process. Contrary to being either uniform or random, the brain does have a complex structure that is specified and repeatable.

A second observation is that the brain contains a large number (approximately 100) of different types of neurons, both in terms of design and function. They are not all identical. That also would not be expected for the smallest brain. A third observation is that small neural networks within the brain control various behaviors, such as the touch response network. It is possible that some of these neural networks are irreducibly complex.

The fourth observation concerns the origin of the C. elegans brain. The usual Darwinian evolution explanation is given in the paper that documented the organization of the synapses, “The mere existence of such structures may actually further underscore the directed evolution to form such clusters, which presumably carry fine functional roles along the neurites. Taken together, local compartmentalized activities, facilitated by the clustered synaptic organizations revealed herein, can enhance computational and memory capacities of a neural network. Such enhancement may be particularly relevant for animals with a compact neural network and with limited computational powers, thereby explaining the evolutionary forces for the emergence of these synaptic organizations.”⁸ The key phrases are “evolutionary forces” and “directed evolution.” Such terms have never been generally accepted as valid scientific explanations, particularly regarding the origin of novel biological structures. 

In contrast, the design of the brain of C. elegans exhibits a number of characteristics associated with intelligent design. They include the specified complexity of the overall design and small neural networks. It also includes engineering design, including the efficient wiring. Also apparent is that a significant amount of information is needed to specify the design and function of the brain.

Notes

1. Cook, et al., “Whole-animal connectomes of both Caenorhabditis elegans sexes,” Nature, Vol. 571, 4 July 2019.
2. McCloskey, et al., “Food responsiveness regulates episodic behavioral states in Caenorhabditis elegans,” J Neurophysiol117: 1911-1934, 2017.
3. Aelon Rahmani and Yee Lian Chew, “Investigating the molecular mechanisms of learning and memory using Caenorhabditis elegans,” Journal of Neurochemistry, 2021; 159.
4. Ruach, et al., “The synaptic organization in the Caenorhabditis elegans neural network suggests significant local compartmentalized computations,” PNAS, 2023, Vol. 120, No. 3.
5. Cook, et al.
6. Witvliet, et al., “Connectomes across development reveal principles of brain maturation,” Nature, Vol. 596, 12 August 2021.
7. Ruach, et al.
8. Ruach, et al.