|Intro to Spinal Cord
Coordinated movement includes the need to contract and relax opposing pairs of muscles ina productive synchrony.
Corticospinal arise from the motor cortex and innervate via one synapse only alpha motor neurons. Voluntary movement.
rubrospinal typically arise in the red nucleus and is involved with reaching and grasping of the limbs and maintaining posture during movement.
Both cortico and rubro are for the transmission of commands for skilled movements.
The tectospinal tract descends from the superior colliculus to cervical levels of the spinal cord and is responsible for the reflec of turning the head in reponse to visual and other stimuli.
reticulospinal activates spinal motor programs for stepping and stereotypic movements. Also, the control of upright body posture.
vestibulospinal is used for the generation of tonic activity in antigravity muscles.
There is a somatotopic organization of the spinal cord where the more proximal muscles are more medial and distal are more later. This is all in the ventral horn for muscle control. Dorsal would be for sensation.
Alpha motor neurons innervate muscle fibers.
There is a temporal summation effect with stimulation of muscle tension. In order to accommodate an essentially linear response to force, there are several kinds of motor units:
Fast fatigable, which can exert high grams of force, but have a rapid decay and then fast-fatique resistant that can respond very quickly as well, but not as powerful and can last longer. Then there is slow, which is never as forceful, but can last long times. In cats, fast fatigable would be used to jump/gallop. fast fatigue resistant would be for running and walking. Slow would be for standing.
The size principle governs which threshold units are recruited first and then which successively after. Since V=IR, and the large the size of the cell, the less resistance, then the same input to a pool of motor neurons will selectively fire the larger neurons first.
In the stretch-reflex, the golgi tendon organs and spindle receptors will sense a stretch, relay to the dorsal root, which will then adjust, via the ventral alpha motor neurons to act accordingly usually by contracting the muscle that is getting stretched and inhibiting the opposing muscle.
What must be noted is that if a muscle is actively contracting, then the spindle will be “unloaded” since it detects “change”. However, if you coactivate gamma (gamma-spindle coactivation) then you can retain information about position as informed by muscle spindles (which wouldn’t have been firing without the gamma). Essentially, gamma will affect the gain of the system. ‘
Golgi tendon organs are also involved in negative feedback regulation. The Ib afferents from tendon organs contact inhibitory interneurons that decrease the activity of alpha motor neurons innervating the same muscle. The Ib inhibitory interneurons also receive input from other sensory fibers, as well as from descending pathways. This arrangement prevents muscles from generating excessive tension and helps maintain a steady level of tone. This also increase the extensor (opposing muscle).
A great way to get a feel for muscle circuitry is by examing the flexion-crossed extension reflex which starts with an input from a cutaneous afferent fiber from a nociceptor . If you step on a tack with your right leg, the circuity will enter the right dorsal root ganglion, excite flexor muscles (hamstrings) and inhibit extensor (quads) so that you can lift up. We also need to extend support to the opposite leg, so we will increase extensor on left leg(quads) and decreasor flexor (hamstrings) so that the opposite leg can support the load.
Breathing and Rhythmic movement
Breathing is a robust and labile behavior.
Eupnea is normal, regular breathing.
The lungs consist of alveoli. They are wet inside, which makes them slightly harder to open due to surface tension. Once your lung collapses, you need to reinflate the lung so it can exchange gas. We sigh about 12 times an hour. Every several minutes we take an uncontrollable large breathe in order to accomadate for this.
With locked-in-syndrome, there is usually a lesion to caudal pons, but lateral movements of the eyes and breathing remains due to their distance from this region.
Dyspnea (breathlessness) is a symptom of cardiopulmonary disease, anxiety, and panic disorders. Neurodegenerative diseases like ALS and parkinsons cause serious breathing problems during sleep.
Sleep disordered breathing is a large problem. Sleep apnea is usually due to central obstructive problems. Our airways are at 90 degress and we have large tongues, so we are not ideally designed for sleep breathing. Loss of muscle tone in upper airways reduces airway caliber and results in snoring.
When your temperature rises, you tend to pant. Panting is the same as thermal polypnea (heat related multiple breathing). You lose heat by panting and get a lot more air and evaporate water from your ventilation. The amount of air in and out is about the same per minute, but you move air more regularly.
the prebotzinger complex has neurons necessary for respiration. The phrenic motoneurons are in the phrenic nucleus. An isolated brainstem (like removing one from a goldfish) shows rhythmic, breath-like activity.
the hypoglossal nerve (XII) can come in and modulate the activity of the prebotzinger complex and increase breathing. Direct glutamate insertion here also excites.
NK1Rs demark the prebotzinger complex. Their birth parallels the adoption of rhythmic breathing. Losing these neurons disturbs breathing. They can’t regulate during sleep. The same problem happens with PD and MSA where they lose NK1R and can’t thrythmically breathe during sleep.
There are two rhtym generators: inspiration and expiration. Diaphragm is for inspiration. Abdomen for expiration. Activating the pRFG enhances abdominal activity. There is an active pumping of air instead of one that cycles. Why two oscillators? Maybe water to air breathing? Maybe development of diaphradm. The most efficient way to move air into a lung if you are a reptile is to actively expire and then relax. However, their lunds are much less complex than ours. Our lung membranes can stretch much further. The development of the diaphragm allowed for accommodation of this increase in surface area and allow for high level oxygenation. This, in turn, allows us to maintain a high temperature and go on to develop big brains. The diaphragm allows for powerful inspiratory efforts and thus more real estate for metabolic processes.
Descending Motor Control
The lateral white matter of the spinal cord consists of white matter from the motor cortex. Medial white matter (ventral) consists of axons from the brain stem.
Brainstem ventral pathway medial motoneurons axial/proximal muscles that support posture and balance
Cortex anterior pathway lateral motorneurons distal muscles for skilled mvoements.
Colliculospinal carries visual and auditory information to the cervical spinal cord for neck movements in response to visual and auditory tracking.
Rubrospinal from the red nucleus helps with precise movements of the fingers (lateral pathway).
reticulospinal helps with postural information in conjunction with the cerebellum
vestibulospinal get info from the semicircular canals about the position and angular acceleration of the head and then goes on to help with posture.
Pyramidal tract lesions affect the use of extremities. This includes paresis (loss of fine movement) and the Babinski reflex.
M1 has a topographical map of body musclulatory and stimulation can activate single muscles. Execution of movement. They converge and diverge onto single muscles.
Premotor/SMA is involved in planning. stimulation brings about complex movement.
Face (more lateral part of the pre-central gyrus) is what forms the corticobulbar.
Primary motor cortex has Betz cells, the largest cells in the brain…necessary for movement. have long axons that make up the corticospinal tract.
A single spike of a cortical motor neuron can cause 9000 spikes in a spinal motor neuron.
There is a direction tuning of upper motor neurons in the primary motor cortex. These neurons fire before and after movement in the preferred direction, but also have a tuning curve to nearby directions. We can take a neuron and calculate its vector (and value) for each direction of movement. Then average those vectors and get the preferred direction.
Autonomic Motor Control
Somatic is mechano to cell body (direct). Sympathetic has autonomic ganglion near the cell body of the spinal cord neuron(far from the target organ). Parasympathetic synapses just near innervation.
Most have their initial cell bodies in the intermediolateral cell column.
Sympathetic primarily uses norepinephrine. Parasymp uses mostly acetylchline and nicotine.
Vagal nucleus sends to gut, heart, striated muscle of throat (pharynx, esophagus, larynx). Nucleus ambiguous sends to heart and throat.
Glossopharyngeal takes from inferior salivatory nucleus in the rostral medulla and feeds the vestibule of mouth (parotid gland).
Nucleus of the solitary tract gets output from the glossopharyngeal with chemoreceptor afferents to carotid bodies. It also sends axons to the preganglionic neurons in the ineteromdeiolateral cell column to then go to sympathetic chain ganglion which then send postganglionic parasympathetic fibers to the heart. This tract also has baroreceptor afferents that innervate the heart.
Nucleus ambiguous via the vagus nerve innervates the cardiac plexus and the SA Node of the heart (nueclueus of solitary tract also reaches here via postganglionic parasympathetic fibers).
Bladder function comes from orbital-medial prefrontal to the midbrain periaqueductal gray (with stops in the amygdala and hypothalamus), then to pontine micruition, then to parasympathetic route for contraction of bladder and to inhibitory local circuits and somatic motor neurons for relaxation of sphincter, etc.
Endothelium derived relaxing factor (Nitrous Oxide) helps to modulate autonomic control of sexual function in the human male. EDRF is a signaling molecule that leads to relaxation of vascular smooth muscle (thus increasing blood flow).
Caudate and putamen make up the striatum.
Substantial nigra pars compacta has dopaminergic projects to the striatum. Reticulata(more ventral in the midbrain) has GABAergic that project outside of basal ganglia (like the superior colliculus).
Basal ganglia are hypothesized to contribute to the automatic execution of movement (sequencing), modulate movement, and select/brake movement.
Direct and Indirect pathways coordinate GO and NO-GO Signals respectively.
Direct is by SNpc to D1 receptors in the striatum (which are excited by the release of dopamine). This then inhibits the globus pallidus internal segment (which has a tonic inhibition on the VA/VL). So, by inhibiting gpi, you disinhibit the thalamus and allow for movement.
Indirect is by NNpc to D2 receptors in the striatum (which are inhibited by the release of dopamine). Indirect is typically inhibiting the Gpe. When you release dopamine, then you see less inhibition of the Gpe which then goes on to inhibt the STN and the Gpi. This works in conjunction with the cortex which will will excite the straitum, which will then allow for Gpe to get inhibited and release its inhibition on the subthalamic which can then go on to excite the Gpi and inhibit movement.
Gpe is tonically inhibiting the STN, which would excite the GPi (and thereby inhibit movement). If you increase activity in the GPe then you decrease STN activity and thus decrease excitation of Gpe and make movement easier.
Dopamine, thus facilitates movement by exerting opposite effects on the direct (increase) and indirect (decrease) pathways.
Medium spiny neurons in putamen and caudate get input from cerebral cortex via glutamate, substantia nigra via dopamine and then go on to wrap around the dendrites (similar to climbing fibers) of globus pallidus.
You can think of a center-surround system where indirect will suppress competing motor programs of opposing muscles and direct will activate intended motor programs.
Damage to striatum make voluntary movements slow and may produce involuntary movements. Huntington’s is marked by loss of striatal GABAergic neurons.
damage to STN could cause large amplitude involuntary movements.
damage to gp could cause slowness of movement, abnormal postures, but does not delay movement initiation.
SNpr could cause abnormal eye movements (has projectiosn to Superior colliculus)
SNpc shows tremor at rest, rigidity, and postural instability. Marked by loss of nigrostriatal dopaminergic neurons (Parkinson’s)
With less dopamine inserted into the striatum, we see less inhibition of the GPi by the direct pathway (the D1 won’t get excited and go on to inhibit). We also see increased inhibition of the Gpe (since the D2 receptors aren’t getting inhbitied by dopamine and their role is to inhibit the Gpe). This then causes less inhibition of the STN and excitement of the GPe, which inhibits movement. This, in turn, makes voluntary movement very hard. This is known as hypokinetic.
Hyperkenetic like Huntingont’s is marked by loss of neurons in the striatum which causes an imbalance between direct andindirect, but D2 are affected first, and thus the indirect pathway. This leads to an inhibition of the STN (Since Gpe is tonically inhibiting the STN and won’t be getting inhibited by the D2 from striatum). This inhibition will decrease its excitement to the Gpi, which will make GPi less inhibited and movement more likely. Also remember that GPe has direct inhibitions to Gpi, so if Gpe is getting disinhibited, then the Gpi is getting inhibited. This is why huntington’s is characterized my huge involuntary movement.
Body movement goes from premotor and somatosensory to putamen to pallidum to thalamus(VL/VA).
occulomotor goes from FEF to caudate to pallidum and SNpr and then to mediodorsal and VA thalamus.
There are also prefrontal loops with RLPFC to caudate to pallidum/ SNpr to MD Thalamus
There are also limbic loops from limbic system to ventral striatum to ventral pallidum to MD thalamus.
All in all, basal ganglia are responsible for the execution of automatic movement sequences. Other mechanisms may intiate, but basal ganglia carry out completion.
Opposing parallel paths adjust the madnitude of the Gpi to increase or decrease movement. Increased Gpi slows movement. Decrease Gpi inreases. Furthermore, selects movement by permitting desired and inhibiting unwanted.
The cerebellum functions as a rapid, corrective feedback loop that smooths and coordinates movements.
Spinocerebellum is vermis. floculus and nodulus are vestibule. rest is cerebro.
Frontal and parietal regions of the cortex project to pontine nuclei, which then cross the midline and enter the cerebellum through the middle cerebellar peduncle to enter into the cerebellar cortex and deep nuclei, which also gets inputs from the inferior olive, the spinal cord, and the vestibular nucleus.
Cerebro is concerned with dentate nucleus for premotor planning. Spino uses fastigial nuclei for motor execution. vestibule uses vestibular nuclei for ocular and vestibule regulation.
Cerebellar cortex projects to deep cerebellar nuclei (dentate/interposed), exit through superior cerebellar peduncle, cross the midline and goes to VL of thalamus and then to primary and premotor cortex.
Other outputs that directly descend do not cross the midline. Cerebellar cortex foes to fastigial nuclei to hit the superior colliculus and reticular formation thatn then travel via the anterior-medial white matter to affect lower motor neurons in the medial ventral horn. Cerebellar cortex goes straight to bestibular nuclei (bypassing the fastigial).
Deep to the molecular later is a single layer of purkinje cells that sit with their axons sprawled in a “Mohawk” type fashion in a saggital view. Purkinjes are the only neurons whose axons leave the cerebellar cortex.
adjacent to the medullary center is the granular layer. Each granule cell send its axon to the molecular layer where it bifurcates to form a fine, unmyleinated parallel fiber that extends along the long axis of the folium and synapses on many purkinjes.
The afferent fibers to the cerebellar cortex are the climbing fibers and the mossy fibers. A single climbing fiber ends directly on one purkinje cell like ivy, climbing up the purkinje’s dendrites. It makes tens of thousands of excitatory synapses, making it the most powerful excitatory input in the entire brain. All of these climbing fibers arise in the contralateral inferior olive of the medulla and enter through the inferior cerebellar peduncle. The rest of the afferents are the mossy fibers which end on the dendrites of granule cells in an indirect route to the purkinje cells.
Purkinje cells axons project to the deep nuclei and some actually leave without hitting these nuclei. The ones that don’t go to the deep nuclei exit via the juxtarestiform and end in the vestibular nuclei. Climbing fibers and mossy fibers also send collateral branches to the deep nuclei. These latter inputs seem to have a tonic excitatory drive for the nuclei and purkinje modulate this firing rate through inhibition.
Still need: stellate/basket
Cortex and spinal cord and vestibular system will feed the mossy fibers which excite granules, which then birth parallel fibers. The mossy fibers also excite the deep cerebellar nuclei. Inferior olive is the sole source of climbing fibers which excite both deep cerebellar nuclei and purkingje cells. Purkinje’s are inhibitory on deep cerebellar nuclei, so there is a clear handshaking that occurs here with inhibition and excitement.
1 climbing fiber innervates about 4-5 purkinje cells. However, 1 Purkinje receive from only 1 climbing fiber. a purkinje also receives input from over 150k mossy fibers since 10 mossy fibers converge on 1 granule cell and one granule cell projects to 80-800 purkinje cells.
Simple spikes are typical action potentionals in a purkinje cell. Complex spikes occur when there is climbing fiber excitation. These complex spikes indicate errors. The rate of complex spikes increases with errors in a novel task. Rate of complex spikes decreases after learning corrects errors in performance. Climbing fibers, thus, function as “teachers” and adaptively shape cerebellar output.
Vestibular input is fast to the deep cerebellar nuclie. Ultrafast to eye movement. but the visual to cerebellar cortex to deep cerebellar nuclei for error correction is slow before there is output to eye movement.
In their air-puff and tone classical conditioning, the tone(CS) is put into the cerebellar system by the mossy fibers. The puff (US) is via the climbing fibers. The deep cerebellar nuclei output to motor systems responsible for the eyelid response.
Parallel fibers witness a removal of AMPA receptors on purkinke cells during learning (particularly simultaneous activation of parallel and climbing on the purkinje cells). So the input from parallel gets weakened.
Mossy fibers come from pons and spinal cord. Climbing fibers are from inferior olive. Purkinje sends to red nucleus, thalamus, inferior olive, and vestibular nuclei.
eye movements bring and hold selected images with the fovea and prevent image slips on the retina.
Abducens nerve contracts the lateral rectus.
occulomotor does medial, superior, inferior, and oblique.
trochlear does superior oblique. (only nerve to exit dorsally)
Vesitbular Ocular Reflex
primary afferents have their cell bodies in the vestibular ganglion, interneurons in the vestibular nuclei, and motor neurons in the abducens, trochlear, and occulomotor nuclei.
the flocculus and the brainstem can cancel our the VOR due to a conscious decision or in the case of a smooth pursuit.
secondary vestibular fibers project sthrough the MLF and adjacent reticular formation to the motor neurons of the oculomotor, trochlear, and abducens
a spin to the left would cause the cupula of the left horizontal canal to bulge toward the utricle and depoalirze the hair cells of this canal and increase CN VIII firing
The left vestibular nuclei would project to the right abducens which would innervate the right lateral rectus and also project to the occulomotor (by way of the MLF) to contract the left medial rectus so that the left eye adducts.
the left vestibular will also inhibit the ipsilateral abducens (so that it’s easier for the occulomotor to adduct via medial rectus contraction). This indirectly causes inhibition of the contralateral occulomotor
The gain of the VOR can be adapted if there is some type of physical affect/ailment. This helps adapt for mechanical changes. Normally the gain is 1 (ratio of head angle vs. eye in head angle).
With the cerebellum, the vestibular signal gets sent to the mossy fibers and then granule cells. The retinal image will come in via the climbing fibers with projections onto both purkinje and the floccular target nucleus which then sends outputs to eye rotation.
The optokinetic reflex uses image slip to rotate the eyes. It’s a bit slow, as it must wait for error before producing movement. It seems to be involved with self-rotation and artificial situations. makes for the sense that the self is moving, not the environment.
The eyes general saccade in order to keep objects of interest on the fovea, which has the highest acuity. The direction is determined by a combinatorial effect of each muscle. It happens in a pulse-step sequence in order to compensate for intertia. the brain suppresses the blur that should occur during a saccade. Subjects are asked to watch a spot on a monitor and then saccade to a new spot. LEDs along the path cannot be seen.
Saccadic eye movements are slower than the VOR to get to target position.
If we need to abduct, then we pulse the abducens and also decrease occulomotor to reduce as much tension as possible.
The saccade circuitry is made up the actual motoneuron and excitatory burst nerions that fire just before movement (in the PPRF) and then also inhibitory bust neurons. There are also long lead burst neurons here that lead up to the movement. There is also an omnipause neuron (in the RIP that gets innervated from the EBN)
The FEF to the superior colliculus to the PPRF (horizontal gaze center in the pons) seems to be responsible for the descending pathway of controlling gaze shifts.
FEF begins responding almost 100ms before the actual saccade. There are particular response fields within the visual field that the FEF neurons will respond to.
You can induce saccades if you stimulate the superior colliculus. There is a mapping of where the saccased will go depending on the tonic mapping of the superior colliculus.
In superior colliculus, the retina projects to the visual layer where there are visual cell dendrites. The visual cell axons project to the motor layer (which has convergence with other inputs). This motor layer then projects to gaze center for saccades.
We achieve a “smooth pursuit” when we are tracking. Without tracking, we make a bunch of mini saccades as we move our eyes across a scene. The evolution of smooth pursuit is thought to parallel development of the fovea. Predators need to keep prey being chased, which were directly ahead, in view. If smooth pursuit needs to move the head, then it can also cancel the VOR.
Smooth pursuit is achieved by PPRF, cerebellum, and nucleus prepostitus hypoglossi. The neurons of the pons are tuned to eye velocity and are directionally selective, and can be stimulated to change the velocity of pursuit. The pontine nuclei project to the cerebellum, specifically the vermis and the paraflocculus. These neurons code for the target velocity and are responsible for the particular velocity profile of pursuit. The cerebellum, especially the vestibulo-cerebellum, is also involved in the online correction of velocity during pursuit. The cerebellum then projects to optic motoneurons, which control the eye muscles and cause the eye to move.
The first step in smooth pursuit is a jolty saccade to the target roughly .25s into the target’s movement in what is known as a “catch-up-saccade”.
In smooth pursuit you want to activate both a lateral rectus and contralateral medial rectus in a velocity dependent manner.