A motor neuron (or motoneuron) is a neuron whose cell body is located in the motor cortex, brainstem, or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly control the effector organs, mainly muscles, and glands.[rx] There are two types of motor neuron – upper motor neurons and lower motor neurons. Axons from upper motor neurons synapse onto interneurons in the spinal cord and occasionally directly onto lower motor neurons.[rx] The axons from the lower motor neurons are efferent nerve fibers that carry signals from the spinal cord to the effectors.[rx] Types of lower motor neurons are alpha motor neurons, beta motor neurons, and gamma motor neurons.
Motor Neuron Classification
MNs are exceptional cell types that can be divided into two main categories according to the location of their cell body: (i) upper and (ii) lower MNs. Upper and lower MNs must be considered as distinct entities despite their shared nomenclature. Neurotransmitter, targeting, and symptoms upon lesion and emphasizes the inappropriateness of a similar appellation to name both entities.
Comparison between upper and lower MNs.
| Upper MNs | Lower MNs | |
|---|---|---|
| Location | Cortex | Brainstem and SC |
| Neurotransmitter | Glutamate | Acetylcholine |
| Targeting | Within the CNS | Outside the CNS |
| Symptoms upon lesion | Spasticity | Paralysis |
Upper and lower MNs diverge in their cell body location, neurotransmitter, targeting and symptoms upon lesion.
Upper motor neurons
Upper motor neurons originate in the motor cortex located in the precentral gyrus. The cells that make up the primary motor cortex are Betz cells, which are a type of pyramidal cell. The axons of these cells descend from the cortex to form the corticospinal tract. Corticomotorneurons project from the primary cortex directly onto motor neurons in the ventral horn of the spinal cord.[rx][rx] Their axons synapse on the spinal motor neurons of multiple muscles as well as on spinal interneurons.[rx][rx] They are unique to primates and it has been suggested that their function is the adaptive control of the hands including the relatively independent control of individual fingers.[rx][rx] Corticomotorneurons have so far only been found in the primary motor cortex and not in secondary motor areas.[rx]
Nerve tracts
Nerve tracts are bundles of axons as white matter, that carry action potentials to their effectors. In the spinal cord, these descending tracts carry impulses from different regions. These tracts also serve as the place of origin for lower motor neurons. There are seven major descending motor tracts to be found in the spinal cord:[rx]
- Lateral corticospinal tract
- Rubrospinal tract
- Lateral reticulospinal tract
- Vestibulospinal tract
- Medial reticulospinal tract
- Tectospinal tract
- Anterior corticospinal tract
Lower motor neurons
Lower MN cell bodies are located in specific nuclei in the brainstem as well as in the ventral horn of the spinal cord and therefore, alike upper MNs, are settling within the CNS. The remarkable characteristic of lower MNs is their axonal extension and connection outside of the CNS. Lower MNs are cholinergic and receive inputs from upper MNs, sensory neurons (SNs) as well as interneurons (INs). Paralysis is a typical clinical symptom of lower MN lesions since once damaged there is no alternative route to convey the information to the muscle targets in the periphery. Lower MNs are classified into three groups according to the type of target they innervate
- (i) branchial,
- (ii) visceral, and
- (iii) somatic MNs.
Lower motor neurons are those that originate in the spinal cord and directly or indirectly innervate effector targets. The target of these neurons varies, but in the somatic nervous system, the target will be some sort of muscle fiber. There are three primary categories of lower motor neurons, which can be further divided into sub-categories.[rx]
According to their targets, motor neurons are classified into three broad categories:[rx]
- Somatic motor neurons
- Special visceral motor neurons
- General visceral motor neurons
Somatic motor neurons
Somatic motor neurons originate in the central nervous system, project their axons to skeletal muscles (such as the muscles of the limbs, abdominal, and intercostal muscles), which are involved in locomotion. The three types of these neurons are the alpha efferent neurons, beta efferent neurons, and gamma efferent neurons. They are called efferent to indicate the flow of information from the central nervous system (CNS) to the periphery.
- Alpha motor neurons – innervate extrafusal muscle fibers, which are the main force-generating component of a muscle. Their cell bodies are in the ventral horn of the spinal cord and they are sometimes called ventral horn cells. A single motor neuron may synapse with 150 muscle fibers on average.[rx] The motor neuron and all of the muscle fibers to which it connects is a motor unit. Motor units are split up into 3 categories:[rx]
- Slow (S) motor units – stimulate small muscle fibers, which contract very slowly and provide small amounts of energy but are very resistant to fatigue, so they are used to sustain muscular contraction, such as keeping the body upright. They gain their energy via oxidative means and hence require oxygen. They are also called red fibers.[rx]
- Fast fatiguing (FF) motor units – stimulate larger muscle groups, which apply large amounts of force but fatigue very quickly. They are used for tasks that require large brief bursts on energy, such as jumping or running. They gain their energy via glycolytic means and hence don’t require oxygen. They are called white fibers.[rx]
- Fast fatigue-resistant motor units – stimulate moderate-sized muscles groups that don’t react as fast as the FF motor units, but can be sustained much longer (as implied by the name) and provide more force than S motor units. These use both oxidative and glycolytic means to gain energy.[rx]
- Beta motor neurons – innervate intrafusal muscle fibers of muscle spindles, with collaterals to extrafusal fibers. There are two types of beta motor neurons: Slow Contracting- These innervate extrafusal fibers. Fast Contracting- These innervate intrafusal fibers.[rx]
- Gamma motor neurons – innervate intrafusal muscle fibers found within the muscle spindle. They regulate the sensitivity of the spindle to muscle stretching. With the activation of gamma neurons, intrafusal muscle fibers contract so that only a small stretch is required to activate spindle sensory neurons and the stretch reflex. There are two types of gamma motor neurons: Dynamic- These focus on Bag1 fibers and enhance dynamic sensitivity. Static- These focus on Bag2 fibers and enhance stretch sensitivity.[rx]
- Regulatory factors of lower motor neurons
- Size Principle – this relates to the soma of the motor neuron. This restricts larger neurons to receive a larger excitatory signal in order to stimulate the muscle fibers it innervates. By reducing unnecessary muscle fiber recruitment, the body is able to optimize energy consumption.[rx]
- Persistent Inward Current (PIC) – recent animal study research has shown that constant flow of ions such as calcium and sodium through channels in the soma and dendrites influence the synaptic input. An alternate way to think of this is that the post-synaptic neuron is being primed before receiving an impulse.[rx]
- After Hyper-polarization (AHP) – A trend has been identified that shows slow motor neurons to have more intense AHPs for a longer duration. One way to remember this is that slow muscle fibers can contract for longer, so it makes sense that their corresponding motor neurons fire at a slower rate.[rx]
Special visceral motor neurons
These are also known as branchial motor neurons, which are involved in facial expression, mastication, phonation, and swallowing. Associated cranial nerves are the oculomotor, abducens, trochlear, and hypoglossal nerves.[rx]
| Branch of NS | Position | Neurotransmitter |
|---|---|---|
| Somatic | n/a | Acetylcholine |
| Parasympathetic | Preganglionic | Acetylcholine |
| Parasympathetic | Ganglionic | Acetylcholine |
| Sympathetic | Preganglionic | Acetylcholine |
| Sympathetic | Ganglionic | Norepinephrine |
| Except for fibers to sweat glands and certain blood vessels Motor neuron neurotransmitters |
||
General visceral motor neurons
These motor neurons indirectly innervate cardiac muscle and smooth muscles of the viscera ( the muscles of the arteries): they synapse onto neurons located in ganglia of the autonomic nervous system (sympathetic and parasympathetic), located in the peripheral nervous system (PNS), which themselves directly innervate visceral muscles (and also some gland cells).
Branchial motor neurons
Branchial MNs are located in the brainstem and form, together with SNs, the cranial nuclei. They innervate branchial arch derived muscles of the face and neck through 5 cranial nuclei: the trigeminal
- (V), facial
- (VII), glossopharyngeal
- (IX), vagus
- (X) and accessory
- (XI) nerves. Despite their similar function, muscles of the neck and the face differ from other skeletal muscles in their embryological origin since they do not derive from the somites, but instead from the branchial arches. Such developmental difference is mirrored by specific characteristics reviewed in depth by Chandrasekhar.
Visceral motor neurons
Visceral MNs belong to the autonomic nervous system (ANS) responsible for the control of smooth muscles (i.e., heart and arteries) and glands. The ANS can be described as the association of two components: (i) preganglionic MNs located in the CNS connected to ganglionic neurons belonging to the peripheral nervous system (PNS). In turn, peripheral ganglionic neurons target the final effector organ. Additionally, the ANS is anatomically and functionally divided into two structures:
- (i) the sympathetic system and
- (ii) the parasympathetic system.
Motor neurons of the sympathetic system.
The sympathetic nervous system is involved in the traditional “fight or flight” responses, recruiting energy storage, increasing awareness, and leading to a global activation of body metabolism. Central MNs of the sympathetic system is located in the spinal cord from the thoracic segment 1 (T1) to the lumbar segment 2 (L2). These MNs have an intermediate-lateral position and constitute the preganglionic column (PGC) that will be described below. They connect to 3 different targets: two chains of ganglia adjacent to the spinal cord named
- (i) paravertebral and
- (ii) prevertebral as well as directly to
- (iii) the chromaffin cells of the adrenal medulla responsible for the release of the catecholamines (i.e., adrenaline and noradrenaline) in the circulation, in response to stress stimuli. On the other hand, paravertebral and prevertebral ganglia connect to a wide variety of targets including the heart, lungs, kidneys, intestines and colon.
Motor neurons of the parasympathetic system
The parasympathetic system controls glands secretion and activates the gastrointestinal tract as well as sexual behavior, which are summarized as “rest and digest” functions. Central MNs of the parasympathetic system are located in the brainstem and contribute to the formation of the cranial nerves (III, VII, IX, and X). Parasympathetic MNs are also found in sacral segments 2 to 4 (S2–S4) of the spinal cord. They innervate ganglia located in the proximity of the peripheral targets such as the heart, bladder, lungs, kidneys, and pancreas.
In summary, visceral central MNs from the sympathetic and parasympathetic systems relay information from the CNS to ganglionic neurons of the PNS. In turn, those ganglia antagonistically control a large number of various visceral targets. In contrast to branchial mentioned previously and somatic MNs described below, visceral MNs do not directly connect to the final effector. As a result, they constitute an anatomical and functional exception among lower MNs.
Somatic motor neurons
Somatic MNs are located in the Rexed lamina IX in the brainstem and the spinal cord and innervate skeletal muscles responsible for movements. MNs form coherent groups connecting to a unique muscle target defined as MN pools. Somatic MNs can be divided into 3 groups:
- (i) alpha,
- (ii) beta, and
- (iii) gamma according to the muscle fiber type they innervate to within a specific muscle target. A motor unit defines a single MN together with all the muscle fibers it innervates. Interestingly, motor units are homogeneous: an MN innervates muscle fibers of a single type. This observation suggests selectivity in the establishment of neuromuscular connectivity and/or a coordinated maturation between an MN and its targeted fibers. Intuitively, the diversity of MNs mirrors the diversity of targets they innervate. Therefore, to better describe somatic MN diversity, a brief description of skeletal muscle physiology will be provided.
Alpha motor neurons
Alpha MNs exclusively innervate extrafusal muscle fibers and are the key to muscle contraction. Anatomically, alpha MNs are characterized by a large cell body and a well-characterized neuromuscular ending. They have an important role in the spinal reflex circuitry by receiving monosynaptic innervation directly from SNs thus minimizing the delay of the response. Alpha MNs can be further divided into 3 different subtypes depending on the extrafusal fiber type they innervate:
- (i) SFR,
- (ii) FFR, and
- (iii) FF. There are no universal criteria distinguishing alpha MNs subtypes; however, some trends are observed in terms of size, excitability, and firing pattern. SFR MNs tend to have a smaller cell body diameter and thus a higher input resistance making them responsive to a lower stimulation threshold. As a result, SFR MNs are recruited first during muscle contraction. They also have the capacity of maintaining a persistent activity even after the stimulation ceased. On the other hand, FF MNs have often a larger cell body and are firing after the initial recruitment of SFR neurons giving extra strength to the activated muscle. In terms of conduction velocity, MNs innervating fast fibers are substantially faster (100 m/s) than SFR MNs (85 m/s). Lastly, little is known about FFR MNs physiology; yet, they are considered to have intermediate characteristics between FF and SFR MNs
Characteristics of alpha and gamma MNs
Schematic showing the principal characteristics of alpha and gamma MNs. Within the ventral spinal cord (SC light gray), MN pools (dashed lines) are composed of gamma MNs (blue) as well as three types of alpha MNs: αFF (light brown), αFFR (dark brown), αSFR (green). Alpha MNs have a larger diameter than gamma MNs. Beta MNs are not represented for simplicity. The proportion of alpha MN subtypes varies between MN pools. In the periphery, a muscle is composed of three types of extrafusal fibers:
- fast-twitch fatigable muscle fibers (light brown, IIb) are innervated by αFF MNs, fast-twitch fatigue-resistant muscle fibers
- (dark brown, IIa) are innervated by alpha αFFR MNs and slow-twitch fatigue-resistant muscle fibers (green, I) are innervated by αSFR MNs.
- Intrafusal muscle fibers (blue) reside within a muscle spindle (gray) and are exclusively innervated by gamma MNs. A single MN innervates multiple fibers all of the same type; however, for schematic simplicity, only one fiber is represented.
Beta motor neurons
Beta MNs are smaller and less abundant than other somatic MN subtypes. As a result, beta MNs are poorly characterized. They innervate both intrafusal and extrafusal muscle fibers. Therefore, beta MNs constitute an exception to the homogeneity observed in motor-units and control both muscle contraction and responsiveness of the sensory feedback from muscle spindles. They are further subdivided into two subtypes depending on the type of intrafusal fibers they innervate:
- (i) static, innervating nuclear chain fibers and
- (ii) dynamic, innervating the nuclear bag fibers of muscle spindles. Static beta MNs increase the firing rate of type Ia and type II sensory fibers at a given muscle length whereas dynamic beta MNs increase the stretch-sensitivity of the type Ia sensory fibers by stiffening the nuclear bag fibers. Beta MNs are mainly characterized by anatomically and functionally, further molecular and electrical properties remain to be identified.
Detailed innervation of a muscle spindle
Schematic of an adult muscle spindle (MS, light gray) on the longitudinal section. Alpha MN (red) exclusively innervates (incoming arrow) extrafusal fibers (EF, brown). Beta MNs (green-brown) innervate both EF and intrafusal fibers (IF, blue). Gamma MNs are divided into two subtypes: static (blue) connecting to nuclear chain (CH, light blue) and nuclear bag 2 (B2, dark blue) fibers and dynamic (purple) connecting to nuclear bag 1 fibers (B1, intermediate blue). Sensory afferent axons Ia (light green) and II (pink) convey information (outgoing arrows) to sensory neurons located in the dorsal root ganglia. The outer capsule (OC) is a dedicated membrane isolating the muscle spindle from the extrafusal fibers. A single MN innervates multiple fibers all of the same type; however, for schematic simplicity, only one fiber is represented.
Gamma motor neurons
Gamma MNs control exclusively the sensitivity of muscle spindles. Their firing increases the tension of intrafusal muscle fibers and therefore mimics the stretch of the muscle. Like beta MNs, gamma MNs are functionally divided into two subtypes:
- (i) static, innervating nuclear chain fibers and static nuclear bag fibers and
- (ii) dynamic, innervating the dynamic nuclear bag fibers. Gamma MNs receive only indirect sensory inputs and do not possess any motor function. Therefore, gamma MNs do not directly participate to spinal reflexes but instead contribute to the modulation of muscle contraction.
References