{{Short description|Interneuron relaying signals between sensory and motor neurons in the spinal cord}} {{Infobox anatomy | Name = Spinal interneuron | Latin = | Image = Anatomy and physiology of animals Relation btw sensory, relay & motor neurons.jpg | Caption = Spinal interneuron integrates sensory-motor input | Image2 = | Caption2 = | IsPartOf = | Components = | Artery = | Vein = }}
A '''spinal interneuron''', found in the [[spinal cord]], relays [[Action potential|signals]] between (afferent) [[sensory neuron]]s, and (efferent) [[motor neurons]]. Different classes of spinal interneurons are involved in the process of [[Sensory-motor coupling|sensory-motor integration]].<ref name=Rose>{{cite journal |vauthors=Rose PK, Scott SH |title=Sensory-motor control: a long-awaited behavioral correlate of presynaptic inhibition |journal=Nature Neuroscience |volume=6 |issue=12 |pages=1243–5 |date=December 2003 |pmid=14634653 |doi=10.1038/nn1203-1243|s2cid=14213819 }}</ref> Most interneurons are found in the [[grey column]], a region of [[grey matter]] in the spinal cord.
==Structure== The [[grey column]] of the [[spinal cord]] appears to have groups of small [[neuron]]s, often referred to as spinal interneurons, that are neither [[Sensory receptor|primary sensory cells]] nor [[motor neuron]]s.<ref name=Marg>{{cite journal |vauthors=Lowrie MB, Lawson SJ |title=Cell death of spinal interneurones |journal=[[Progress in Neurobiology]] |volume=61 |issue=6 |pages=543–55 |date=August 2000 |pmid=10775796 |doi=10.1016/S0301-0082(99)00065-9|s2cid=36074193 }}</ref> The versatile properties of these spinal interneurons cover a wide range of activities. Their functions include the processing of [[Sensory processing|sensory]] input, the modulation of motor neuron activity, the coordination of activity at different spinal levels, and the relay of sensory or [[Proprioception|proprioceptive]] data to the [[brain]]. There has been extensive research on the identification and characterization of the spinal cord interneurons based on factors such as location, size, structure, connectivity, and function.<ref name=Marg /> Generally, it is difficult to characterize every aspect of the neuronal anatomy of a vertebrate's spinal cord. This difficulty is due not only to its structural complexity but also to the morphology and the connectivity of neurons. For instance, in the spinal cord of a 19-day-old rat embryo, at least 17 different subclasses of interneurons with [[ipsilateral]] [[axon]] projections were found. In addition, 18 types of [[Commissure|commissural]] interneurons have been identified on the basis of [[Neuromorphology|morphology]] and location.<ref name="Silso 1992">{{cite journal |vauthors=Silos-Santiago I, Snider WD |title=Development of commissural neurons in the embryonic rat spinal cord |journal=The Journal of Comparative Neurology |volume=325 |issue=4 |pages=514–26 |date=November 1992 |pmid=1469113 |doi=10.1002/cne.903250405|s2cid=33624862 }}</ref><ref name="Silso 1994">{{cite journal |vauthors=Silos-Santiago I, Snider WD |title=Development of interneurons with ipsilateral projections in embryonic rat spinal cord |journal=The Journal of Comparative Neurology |volume=342 |issue=2 |pages=221–31 |date=April 1994 |pmid=8201033 |doi=10.1002/cne.903420206|s2cid=24821413 }}</ref>
=== Location ===
In particular, the [[Soma (biology)|cell bodies]] of the spinal interneurons are found in the grey matter of the spinal cord, which also contains the motor neurons. In 1952, the grey matter of the cat's spinal cord was investigated, and it was shown to have ten distinct zones referred to as [[Rexed laminae]]. Eventually, the lamination pattern was also observed in several species including humans. [[Rexed laminae|Rexed laminae VII]] and [[Rexed laminae|VIII]] are locations where most of the interneurons are found.<ref name=GH>{{cite book|last=Goshgarian|first=HG|title=Neuroanatomic Organization of the Spinal Gray and White Matter|year=2003|publisher=Demos Medical Publishing|location=New York|url=https://www.ncbi.nlm.nih.gov/books/NBK9443/}}{{dead link|date=July 2025|bot=medic}}{{cbignore|bot=medic}}{{page needed|date=May 2014}}</ref> [[File:Medulla spinalis - Substantia grisea - English.svg|thumbnail|center|Rexed laminae]]
==Development==
In the mouse's [[Dorsal (anatomy)|dorsal]] [[alar plate]], six [[Progenitor cell|progenitor]] domains give rise to [[dI1-dI6]] neurons and two classes of dorsal interneurons.<ref name=Circuit>{{cite journal |author=Goulding M |title=Circuits controlling vertebrate locomotion: moving in a new direction |journal=Nature Reviews. Neuroscience |volume=10 |issue=7 |pages=507–18 |date=July 2009 |pmid=19543221 |pmc=2847453 |doi=10.1038/nrn2608}}</ref> In addition, in the [[Anatomical terms of location|ventral]] half of the neural tube, four classes of (CPG) interneurons known as [[V0 neuron|V0]], [[V1 neuron|V1]], [[V2 neuron|V2]], and [[V3 neuron|V3]] neurons are generated.<ref name=Circuit /> V0 neurons are [[Commissure|commissural]] neurons that extend their axons [[Anatomical terms of location|rostrally]] for 2-4 spinal cord regions in the embryonic spinal cord.<ref name=Circuit /> V3 neurons are excitatory commissural interneurons that extend [[Anatomical terms of location|caudally]] projecting primary axons.<ref name=Circuit /> The V1 neurons are inhibitory interneurons with axons that project [[Anatomical terms of location|ipsilaterally]] and [[Anatomical terms of location|rostrally]].<ref name=Circuit /> V2 neurons, which include a population of [[glutamatergic]] [[V2a neurons]] and inhibitory [[V2b neurons]], project ipsilaterally and caudally across multiple spinal cord regions.<ref name=Circuit /> The class V1 neurons give rise to two [[Interneuron|local]] circuit inhibitory neurons known as Renshaw cells and Ia inhibitory interneurons.<ref name=Circuit /> {| class="wikitable" |- ! CPG interneurons !! Type !! Axon projection in embryonic cord |- | V0 || Commissural || [[Anatomical terms of location|Rostrally]] |- |V1 || Inhibitory (Renshaw cells and Ia interneurons) || Rostrally and [[Anatomical terms of location|ipsilaterally]] |- | V2 || Glutamatergic V2a and Inhibitory V2b || Ipsilaterally and [[Anatomical terms of location|caudally]] |- | V3 || Excitatory Commissural || Caudally |-
|}
==Function==
The integration of the sensory feedback [[Action potential|signals]] and central motor commands at several levels of the [[central nervous system]] plays a critical role in controlling movement.<ref name=Nielsen>{{cite journal |author=Nielsen JB |title=Sensorimotor integration at spinal level as a basis for muscle coordination during voluntary movement in humans |journal=Journal of Applied Physiology |volume=96 |issue=5 |pages=1961–7 |date=May 2004 |pmid=15075316 |doi=10.1152/japplphysiol.01073.2003}}</ref> Research on cat's spinal cord has shown that at the spinal cord level [[Afferent nerve fiber|sensory afferents]] and descending [[Pyramidal tracts|motor pathways]] converge onto common spinal interneurons.<ref name=Nielsen /> Human studies since the 1970s have documented how this integration of motor commands and sensory feedback signals is used to control [[Muscle contraction|muscle activity]] during movement.<ref name=Nielsen /> During locomotion, the sum of convergent inputs from the [[central pattern generator]] (CPG), sensory feedback, descending commands and other intrinsic properties turned on by different [[Neuromodulation|neuromodulators]] give rise to the activity of the interneurons.<ref name=Serge>{{cite journal |vauthors=Rossignol S, Dubuc R, Gossard JP |title=Dynamic sensorimotor interactions in locomotion |journal=Physiological Reviews |volume=86 |issue=1 |pages=89–154 |date=January 2006 |pmid=16371596 |doi=10.1152/physrev.00028.2005}}</ref> Further, this interneuronal activity was either recorded directly or inferred from the modulation of response in their postsynaptic targets, most often motoneurons.<ref name=Serge/> The most efficient way to gate sensory signals in reflex pathways is to control the firing level of interneurons. For example, during locomotion, the interneuronal activity is modulated via excitation or inhibition depending on the reflex pathways.<ref name=Serge/> Thus, different patterns of interneuronal activity will determine which pathways are open, blocked, or modulated.<ref name=Serge/>
=== Neurotransmitter ===
The sensory information that is transmitted to the spinal cord is modulated by a complex network of [[Neurotransmitter#Excitatory and inhibitory|excitatory]] and [[Neurotransmitter#Excitatory and inhibitory|inhibitory]] interneurons. Different neurotransmitters are released from different interneurons, but the two most common neurotransmitters are [[GABA]], the primary [[inhibitory]] neurotransmitter and [[glutamate]], the primary [[excitatory]] neurotransmitter.<ref name=":0">{{cite journal|last1=Manent|first1=Jean-Bernard|last2=Represa|first2=Alfonso|title=Neurotransmitters and Brain Maturation: Early Paracrine Actions of GABA and Glutamate Modulate Neuronal Migration|journal=The Neuroscientist|date=1 June 2007|volume=13|issue=3|pages=268–279|doi=10.1177/1073858406298918|pmid=17519369|s2cid=17362858 |url=http://www.hal.inserm.fr/inserm-00483861|url-access=subscription}}</ref><ref>{{cite journal |vauthors=Bardoni R, Takazawa T, Tong CK, Choudhury P, Scherrer G, Macdermott AB |title=Pre- and postsynaptic inhibitory control in the spinal cord dorsal horn |journal=Annals of the New York Academy of Sciences |volume=1279 |pages=90–6 |date=March 2013 |issue=1 |pmid=23531006 |doi=10.1111/nyas.12056|pmc=7359868 |bibcode=2013NYASA1279...90B }}</ref> [[Acetylcholine]] is a neurotransmitter that often activates interneurons by binding to a receptor on the membrane.<ref>{{cite journal|last1=Alkondon|first1=M|last2=Peirera|first2=EF|last3=Eisenberg|first3=HM|last4=Albuquerque|first4=EX|title=Nicotinic receptor activation in human cerebral cortical interneurons: a mechanism for inhibition and disinhibition of neuronal networks|journal=Journal of Neuroscience|date=1 January 2000|volume=20|issue=1|pages=66–75|pmid=10627582|pmc=6774099|doi=10.1523/jneurosci.20-01-00066.2000}}</ref>
===Cell types===
=== Renshaw cells === [[Renshaw cells]] are among the first identified interneurons.<ref name=H>{{cite journal |vauthors=Nishimaru H, Kakizaki M |title=The role of inhibitory neurotransmission in locomotor circuits of the developing mammalian spinal cord |journal=Acta Physiologica |volume=197 |issue=2 |pages=83–97 |date=October 2009 |pmid=19673737 |doi=10.1111/j.1748-1716.2009.02020.x|s2cid=34421703 }}</ref> This type of interneuron projects onto [[Alpha motor neuron|α-motoneurons]], where it establishes inhibition by expressing its inhibitory neurotransmitter glycine.<ref name=H /><ref name=Hans>{{cite journal |author=Hultborn H |title=Spinal reflexes, mechanisms and concepts: from Eccles to Lundberg and beyond |journal=Progress in Neurobiology |volume=78 |issue=3–5 |pages=215–32 |year=2006 |pmid=16716488 |doi=10.1016/j.pneurobio.2006.04.001|s2cid=25904937 }}</ref> However, some reports have indicated that Renshaw cells synthesize calcium-binding proteins [[Calbindin|calbindin-D28k]] and [[parvalbumin]].{{Clarify | date = October 2019 | reason = It's not obvious how this relates to the prior sentence, the following setence, or the rest of the paragraph. Or maybe better to just drop/change some of the connecting words like 'however' or 'further', etc?}} Further, during [[spinal reflex]], Renshaw cells control the activity of the spinal motoneurons. They are excited by the [[axon collaterals]] of the motor neurons. In addition, Renshaw cells make inhibitory connections to several groups of motor neurons, Ia inhibitory interneurons as well as the same motor neuron that excited them previously.<ref name=Hans /> Furthermore, the connection to the motor neurons establishes a [[negative feedback]] system that may regulate the [[Action potential|firing rate]] of the motor neurons.<ref name=Hans /> Moreover, the connections to the Ia inhibitory interneurons may modulate the strength of the [[reciprocal inhibition]] to the antagonist motor neuron.<ref name=Hans />
=== Ia inhibitory interneuron ===
Joints are controlled by two opposing sets of muscles called [[Extensor muscle|extensors]] and [[Hip flexors|flexors]] that must work in synchrony to allow proper and desired movement.<ref name=James>{{cite book|last=Knierim|first=James|title=Spinal Reflexes and Descending Motor Pathways|year=2013|publisher=UTHealth|location=Houston|url=http://neuroscience.uth.tmc.edu/s3/chapter02.html}}{{page needed|date=May 2014}}</ref> When a [[muscle spindle]] is stretched and the [[stretch reflex]] is activated, the opposing muscle group must be inhibited to prevent from working against the agonist muscle.<ref name=H /><ref name=James/> The spinal interneuron called Ia inhibitory interneuron is responsible for this inhibition of the antagonist muscle.<ref name=James/> The Ia afferent of the muscle spindle enters the spinal cord, and one branch [[synapses]] on to the alpha motor neuron that causes the agonist muscle to contract.<ref name=James/> Thus, it results in creating the behavioral reflex.
At the same time, the other branch of the Ia afferent [[synapses]] on to the Ia inhibitory interneuron, which in turn synapses the [[alpha motor neuron]] of the antagonist muscle.<ref name=James/> Since Ia interneuron is inhibitory, it prevents the opposing alpha motor neuron from firing. Thus, it prevents the antagonist muscle from contracting.<ref name=James/> Without having this system of [[reciprocal inhibition]], both groups of muscles may contract at the same time and work against each other. This results in spending a greater amount of energy as well.
In addition, the reciprocal inhibition is important for mechanism underlying voluntary movement.<ref name=James/> When the antagonist muscle relaxes during movement, this increases efficiency and speed. This prevents moving muscles from working against the contraction force of antagonist muscles.<ref name=James/> Thus, during voluntary movement, the Ia inhibitory interneurons are used to coordinate muscle contraction.
Further, the Ia inhibitory interneurons allow the higher centers to coordinate commands sent to the two muscles working opposite of each other at a single joint via a single command.<ref name=James/> The interneuron receives the input command from the [[Pyramidal tracts|corticospinal descending axons]] in such a way that the descending signal, which activates the contraction of one muscle, causes relaxation of the other muscles.<ref name=H /><ref name=Hans /><ref name=James/><ref name=":1">{{cite book |vauthors=Nógrádi A, Vrbová G |title=Anatomy and Physiology of the Spinal Cord |url=https://www.ncbi.nlm.nih.gov/books/NBK6229/|publisher=Landes Bioscience |year=2013 }}{{page needed|date=May 2014}}</ref>
=== Ib inhibitory interneuron ===
The [[autogenic inhibition reflex]] is a spinal reflex phenomenon that involves the [[Golgi tendon organ]].<ref name=James/> When tension is applied to a muscle, group Ib fibers that innervate the Golgi tendon organ are activated. These afferent fibers project onto the spinal cord and synapse with the spinal interneurons called Ib inhibitory interneurons.<ref name=James/> This spinal interneuron makes an inhibitory synapse onto the alpha motor neuron that innervates the same muscle that caused the Ib afferent to fire. As a result of this reflex, activation of the Ib afferent causes the alpha motor neuron to become inhibited. Thus, the contraction of the muscle stops.<ref name=James/> This is an example of a [[disynaptic reflex]], in which the circuitry contains a spinal interneuron between the sensory afferent and the motor neuron.<ref name=Hans /><ref name=James/>
The activities of the extensor and flexor muscles must be coordinated in the autogenic inhibition reflex. The Ib afferent branches in the spinal cord. One branch synapses the Ib inhibitory interneuron. The other branch synapses onto an excitatory interneuron. This excitatory interneuron innervates the [[alpha motor neuron]] that controls the antagonist muscle. When the agonist muscle is inhibited from contracting, the antagonist muscle contracts.<ref name=James/>
=== Excitatory interneurons mediating cutaneous inputs === An important reflex initiated by [[cutaneous receptor]]s and [[pain receptor]]s is the [[flexor reflex]].<ref name=James/> This reflex mechanism allows for quick withdrawal of the body parts, in this case a limb, from the harmful stimulus. The signal travels to the spinal cord and a response is initiated even before it travels up to the brain centers for a conscious decision to be made.<ref name=James/> The reflex circuit involves the activation of the [[A delta fiber|Group III afferents]] of pain receptors due to a stimulus affecting a limb, e.g. a foot. These afferents enter the spinal cord and travel up to the [[lumbar region]], where they synapse an excitatory interneuron.<ref name=James/> This interneuron excites the alpha motor neuron that causes contraction of the thigh flexor muscle.
Also, [[Muscle spindle|Group III afferent]] travels up to [[Vertebral column|L2 vertebra]], where they branch onto another excitatory interneuron. This interneuron excites the alpha motor neurons, which then excite the [[Hip flexors|hip flexor muscle]].<ref name=James/> This synchronized communication allows for the removal of the whole leg from the painful stimulus. This is an example of the spinal cord circuitry coordinating movement at several joints simultaneously. In addition, during flexor reflex, when the [[Knee|knee joints]] and hip joints are flexed, the antagonist extensor muscles must be inhibited.<ref name=James/> This inhibitory effect is achieved when Group III afferents synapse inhibitory interneurons that in turn synapse the alpha motor neurons innervating the antagonists muscle.<ref name=James/>
The flexor reflex not only coordinates the activity of the leg being removed but also the activity of the other leg. When one leg is removed, the weight of the body needs to be distributed to the opposite leg to maintain the body's balance. Thus, the flexor reflex incorporates a [[crossed extension reflex]]. A branch of the Group III afferent synapse an excitatory interneuron, which extends its axon across the midline into the [[Anatomical terms of location|contralateral]] spinal cord. At that location, the interneuron excites the alpha motor neurons that innervate the extensor muscles of the opposite leg. This allows for balance and body posture to be maintained.<ref name=James/>
=== Excitatory commissural interneurons === A group of commissural interneurons present in lamina VIII in mid-lumbar segments mediates excitation of contralateral motoneurons by reticulospinal neurons.<ref name=":0" /> These neurons receive monosynaptic inputs from ipsilateral reticular formation and are not directly activated by group II afferents.<ref name=":1" />
Another class of lamina VIII commissural neurons includes a group that is activated by both reticulospinal and vestibular systems. These cells can also be activated indirectly by group I and group II afferents.<ref>{{Cite journal |last1=Maxwell |first1=David J. |last2=Soteropoulos |first2=Demetris S. |date=2020-01-01 |title=The mammalian spinal commissural system: properties and functions |journal=Journal of Neurophysiology |volume=123 |issue=1 |pages=4–21 |doi=10.1152/jn.00347.2019 |issn=1522-1598 |pmc=6985854 |pmid=31693445}}</ref> These cells have also been shown to be active during locomotion.
== References == {{reflist}}
[[Category:Neurons]] [[Category:Spine]] [[Category:Neuroanatomy]]