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The Vertebral Column and Spinal Cord  The Vertebral Column Dorsal spinous Vertebral Canal Process The spinal cord is surrounded by...

The Vertebral Column and Spinal Cord  The Vertebral Column Dorsal spinous Vertebral Canal Process The spinal cord is surrounded by the VERTEBRAL COLUMN, a Articular Process boney structure that protects the nervous tissue while allowing Transverse movement. Process The vertebral column is composed of individual boney elements called vertebrae (singular: vertebra) whose central cavities, when lined up, form the spinal or vertebral canal. Images from: Compendium 3: 639, 1981 The Vertebral Column Divided into Regions: Cervical, thoracic, Lumbar, Sacral, Coccygeal. Minor species differences exist in number and shape of vertebrae in each region. Canine: C-7, T-13, L-7, S-3, Cg~20. AtestA * some animals have extra lumbar vertebrae  The Vertebral Column Adjacent vertebrae (except sacral and coccygeal) are separated by intervertebral discs These act as “shock absorbers” and points of gallikesubstance flexion/extension which Annulus Fibrosis help allow the spine to move uniformly without nashvillevetspecialists.com thick" outer ring compromising the spinal cord The Vertebral Column Prolapse of intervertebral discs and subsequent neurological signs is a major clinical syndrome in dogs. Called intervertebral disc disease (IVDD) X Localizing and treating/ managing theses diseases is often a significant clinical challenge. www.vetmedcenter.com  The Vertebral Column Prolapse of intervertebral discs and subsequent neurological signs is a major clinical syndrome in dogs. Called intervertebral disc disease (IVDD) Localizing and treating/ managing theses diseases is often a significant clinical challenge. y Interesting video from UCSF: www.vetmedcenter.com http://www.youtube.com/ watch?v=hlBvhlL-X98 narrower-bones closer together scauses what was there to move up : causing ↑ opacity above  The Vertebral Column: Atlas, Axis 1st and 2nd cervical vertebrae have evolved modified structure to support skull and allow enhanced movement compared to the rest of the vertebral column. No intervertebral disc is present between C1 and the skull nor between C1 and C2. anatomy.wikispaces.com Atlas-holds head Axis - mouvement The Vertebral Column: The Sacrum B cows have horses xS 3 Sacral vertebrae are fused to form a single boney structure with defined foramina through which nerves pass. Species variation in numbers fused: 3 dog and cat, 5 horse and cow. From: Khalil, tuskegee.edu  Meninges * test A set of 3 tissue membranes surrounding brain and spinal cord. Provide protection, support for blood vessels and containment of cerebrospinal fluid (CSF) Membranes – Dura mater: outermost layer, strongest – Pia mater: bound tightly to surface of brain and spinal cord, most blood vessels present in this layer – Arachnoid mater: thin, “spiderweb” of membranes between pia and dura. Spaces – Epidural: external to the dura Anesthestics injected here – Subdural space: serous fluid – Subarachnoid: between pia and arachnoid - Filled with CSF  Spinal Cord A column-shaped continuation of the brainstem (medulla), extending from the foramen magnum (base of the skull) to the lumbar region of the vertebral column. Runs through the vertebral canal Regions – Cervical (C) – Thoracic (T) – Lumbar (L) – Sacral (S) – Caudal (Cd) Gives rise to spinal nerves – All spinal nerves are mixed nerves (sensory and motor) ↳ nerves fused into vanat.cvm.umn.edu  Spinal Cord comes Spinal Nerves: Paired dosat structures (L and R) formed all sensory o from the fusion of the dorsal ↑ and ventral nerve roots at each level of the spinal cord. The region of the spinal cord from which they originate Fused defines a “spinal segment” (eg. nong C6 segment is the source of 4 info the C6 spinal nerves) motor leaves.lumenlearning.com Spinal nerves extend out of the ventral rost A vertebral column via the TESTE A No ON intervertebral foramina ganglion between adjacent vertebrae  Spinal Cord The rea of skin innervated by the sensory fibres from an individual spinal nerve/spinal segment is called a dermatome. Similarly, the muscles innervated by the motor fibres from an individual spinal nerve/segment Bovine dermatomes is called a myotome.  Spinal Cord: Anatomical Features Cl - C7 - > nerves leaves in front of vertebrae Spinal segments do not correspond exactly with “equivalent” vertebrae. There is an additional cervical spinal SEGMENT relative to the number of cervical VERTEBRAE. As a result, spinal nerves exit the vertebral canal via the intervertebral foramen cranial to the vertebra after which they are named between C1 and C7….. Then C8 exits caudal to the 7th cervical vertebra….. C7 SN C7 Vert Then all subsequent spinal nerves exit caudal to the vertebra after which they are C8 SN named (T1-T13, L1-L7, S1-S3, etc.) vanat.cvm.umn.edu  Spinal Cord: Anatomical Features The caudal spinal segments of spinal cord are smaller than the cranial segments. Caudal spinal This results in the spinal cord ending segments cranial to the end of the vertebral column, with the terminal spinal segments found clustered in a short stretch of the spinal canal in the area of L4 – L6 (vertebrae) The spinal nerves from the terminal segments course caudally and form a structure called the cauda equina which occupies the canal caudal to L6 (vertebra) vanat.cvm.umn.edu  Spinal Cord: Anatomical Features Spinal cord is not uniform in diameter along entire length Cervical (cervicothoracic) enlargement: Spinal segments that supply nerves to forelimbs (Segments C6, C7, C8, T1, (T2)) Lumbosacral enlargement: Spinal segments that supply nerves to hindlimbs (Segments: L4, L5, L6, L7, S1 (S2)) vanat.cvm.umn.edu Spinal Cord: Gray and White Matter of myellin mattera prense Axons-white matter neurons-grey Any given cross section of the spinal cord contains a central area of gray matter and an outer area of white matter. - Rutgers  Spinal Cord: Gray and White Matter Gray matter: Primarily composed of neuron cell bodies Dorsal column Divided into gray matter horns: Dorsal horn (Sensory neurons (2°)) Ventral horn (Motor neurons (1°)) Lateral horn (Autonomic neurons - in thoracic and first few lumbar and sacral segments only) NS ↳ only in autonomic Lateral horn White matter: Primarily composed of axons. Divided into white matter columns (or funiculi) which contain Lateral column individual tracts (axons carrying specific type of “information” (sensory or motor)): Ventral column Dorsal column (Sensory tracts) Lateral column (Mix of sensory and motor tracts) Ventral column (Mix of sensory and motor tracts)  Spinal Cord: Gray Matter Horns Types of neurons in the different gray matter horns is consistent with their relationship to the dorsal and ventral Dorsal horn roots. The dorsal root is where axons from sensory neuron enter the spinal cord, so the first neurons that they usually synapse upon (called a 2° neuron) are the first neurons encountered. Similarly, the ventral root is where axons of motor neuron exit the spinal cord, and Ventral horn the nerve cell bodies where these axons.lumenlearning.com originate are physically close to this root.  Spinal Cord: White Matter Tracts Tracts: Specific neuronal pathways in white matter through which action potentials relaying specific types of information (sensory, motor) pass. Organized somatotopically, meaning there is a strict relationship between where the tract/neuron is and the kind of information it conducts or mediates. This extends to other areas of the CNS, where there is a specific regional distribution of the function of neurons. This is why, when a specific area of spinal cord is injured, there are specific signs that can be explained by the damage to specific neuron types (both in tracts and in gray matter).  Spinal Cord: White Matter Tracts Importance: Understanding the significance of somatotopic structure of tracts will help you to understand why regional injuries/diseases lead to specific signs, to localize lesions based on those signs and sometimes, to predict the course/progress of a particular disease based on the tracts affected.  Spinal Cord: White Matter Tracts “General” Features Tracts are anatomically and functionally distinct from each other – each carries a specific “type” of sensory or motor information Most consist of a chain of two or three neurons Tracts are often named according to where they originate and terminate (eg. spinothalamic tract contains axons relaying APs from the spinal cord to the thalamus). Neurons in tracts often (but not always) decussate (cross over) at some point in the pathway between the spinal cord and brain. All pathways are paired: one tract on left and right sides of the spinal cord Spinal Cord: White Matter Tracts Note: Tracts are BILATERAL even though sensory tracts are shown on left side and motor tracts on the right in this image.  Spinal Cord: Blood Supply Spinal cord is segmentally supplied by branches that arise from the vertebral artery (in cervical and anterior thoracic regions), the intercostal artery (in thoracic region), and the aorta (in lumbar region) that feed into three arteries that run the length of the cord: 1) A single ventral spinal artery - follows ventral surface of cord. 2) Paired dorsolateral spinal arteries - run along base of dorsal roots of spinal nerves. Radial branches split off these arteries, supplying the core of the spinal cord.  A no diagrams on exams Spinal Cord: Blood Supply Dorsolateral Spinal artery Ventral Spinal artery Radial branch Dorsolateral Spinal artery Ventral Intercostal arteries Spinal artery  Spinal Cord: Blood Supply - Damage Fibrocartilagenous embolic myelopathy (FCEM): Disruption of the blood supply to a segment or segments of the spinal cord due to vascular obstruction by cartilage fragments, usually from the intervertebral disc. http://www.petsurgery.com/ Spinal Reflexes student.blogspot.com  The Reflex Arc A Reflex Arc is a simple neuronal circuit in which a sensory neuron enters the CNS and, after one or more synapses, leads to an action potential in a motor neuron and a detectable response in an effector organ such as a muscle. The Reflex Arc: Relevant Microanatomy Recall that neurons “communicate” via synapses…… Reflexes involve at least one (and often more) synapse(s)  The Reflex Arc: Relevant Anatomy Also recall the two main divisions of the nervous system. Brain and spinal cord: Central Nervous System (CNS) Peripheral nerves and ganglia: Peripheral Nervous System (PNS) Somatic reflexes start and end in the PNS, but the synapse(s) are in the CNS (the arc enters and exits the CNS)  The Reflex Arc: Relevant Anatomy Finally, remember that paired Spinal Nerves enter and exit the spinal cord at each spinal level and reflexes can occur on each side at each level (as well as the brain)..lumenlearning.com Spinal reflexes are present on both sides of the animal and occur along the length of the spinal cord. Their presence reflects the activity in the PNS and/or in the CNS at the level they enter and leave the spinal cord.  The Reflex Arc Components of most reflex arcs: 1) Sensory receptor 2) Sensory neuron 3) Interneuron (not always present) 4) Motor neuron 5) Effector organ Reflexes: Classification/Terminology Effector division (Does it involve skeletal or smooth muscle?) – Somatic (Skeletal muscle) – Autonomic (Smooth muscle) Integration site (Where in the CNS are the neurons and synapses involved?) – Spinal Cord – Spinal Reflexes – Brain – Cranial Nerve Reflexes Number of synapses/neurons (How many neurons in pathway?) – Monosynaptic > - 1 – Polysynaptic It > -  Reflexes: Common Spinal Reflexes this > - withdraw) reflex know 16/09/20 8  Common Spinal Reflex Types Types of Reflex Arc Monosynaptic Multisynaptic Multisynaptic Ipsilateral (same side) Ipsilateral (same side) Contralateral (opposite side)  Common Spinal Reflex Types Myotatic (stretch) reflex: Tap patellar tendon, observe rapid extension of the knee Monosynaptic Ipsilateral (Same Side) e.g. Patellar (knee-jerk) reflex Muscle stretch stimulates muscle spindle à sensory neuron synapses with motor neuron to same muscle  Common Spinal Reflex Types Flexor Reflex (Withdrawal Reflex): Pinch toe and observe flexion of the leg Multisynaptic Ipsilateral (same side as stimulus) Response to pain in limb à flexors in same limb contract  Common Spinal Reflex Types Crossed-extensor reflex: Pinch toe (like flexor reflex) and observe extension of the opposite leg Multisynaptic Contralateral (opposite side) Response to pain in limb àextensors in opposite limb contract and extend leg.  Basis for a Simple Monosynaptic Reflex: The Muscle Spindle Muscle spindle organ (Intrafusal fibre) Intrafusal fibre - A type of mechanoreceptor - Fires when muscle stretched, stops when muscle shortens - “Senses” muscle length and sends that signal to the CNS  Basis for a Simple Monosynaptic Reflex: The Muscle Spindle Response to Stretch à Sensory fibre synapses directly with alpha motor neuron Intrafusal fibre à Muscle contraction à Maintenance of posture through muscle tension à Gamma motor then neuron tenses the intrafusal fibre to just below threshold tension Sensor has to be ready to respond regardless of position  Reflexes in the Clinical Context Because they are present at individual spinal levels, and in many cranial nerves, reflex arcs form the basis of a very significant portion of the clinical neurologic examination of our patients. Evaluating reflexes helps us determine where a lesion is in the nervous system and obtain some sense of how severe the problem is.  Reflexes in the Clinical Context The video at the URL below is worth a look, even though you may not yet understand all the details! http://www.youtube.com/watch?v=NFqFABsIa7Q Spinal Tracts  Spinal Tracts “General” Features of All Tracts Tracts are anatomically and functionally distinct from each other. Ascending tracts carry sensory information to the brain, descending tracts carry motor information from the brain. Most consist of a connected series of two or three neurons Tracts are often named according to where they originate and terminate (eg. spinothalamic tract contains axons relaying APs from the spinal cord to the thalamus). Neurons in tracts often (but not always) decussate (cross over) at some point in the pathway between the spinal cord and brain. All pathways are paired: one tract on left and right sides of the spinal cord Ascending (Sensory, Afferent) Tracts: General Features The primary neuron ALWAYS enters the spinal cord via the dorsal root. The primary neuron's (nerve) cell body is ALWAYS in the Dorsal Root Ganglion. Sensory information usually crosses the midline (decussates) to the CONTRALATERAL side. Exception: some proprioception fibres - the axon enters the spinal cord and ascends on the same (IPSILATERAL) side.  Ascending Tracts Carrying Conscious Sensory Information In veterinary medicine we consider two “defined” primary sensory tracts carrying conscious sensation (sometimes called GSA: general somatic afferent) and a third poorly defined group of tracts. Spinothalamic (AKA: Anterolateral, Ventrolateral) Tract: Relays action potentials carrying pain and temperature “information”. Located in the ventrolateral areas of the spinal cord white matter. Carries pain and temperature sensations in fibres of moderate or small diameter and myelination Relatively resistant to injury  Ascending Tracts Carrying Conscious Sensory Information Dorsal Column (AKA Fasciculus Cuneatus and Fasciculus Gracilis): Carry information concerning conscious proprioception (ie: where limbs are in space), touch. Located at the most dorsal aspect of the spinal cord, it includes the medial Fasciculus Gracilis (hindlimbs, caudal to T6) and the more lateral Fasciculus Cuneatus (forelimbs, cranial to T6). Composed of large myelinated fibres. Information travelling in these tracts ultimately ascends to the cortex (after several synapses in other brain areas). These fibres have a relatively high susceptibility to injury due to myelination and location. if damaged you will see: * Ataxia /flip , Knuckling paw over & they don't flip it back) Defined Conscious Sensory Pathways/Tracts  Ascending Tracts Carrying Conscious Sensory Information Non-specific, multisynaptic pathways There are several poorly-defined pathways, with different names that ascend bilaterally in the spinal cord, usually involving poorly myelinated neurons. These poorly defined tracts ascend in white matter throughout the spinal cord and terminate as part of the reticular activating system (RAS) in the brain. They synapse multiple times as they ascend and, because of their wide distribution and low myelination, appear resistant to injury. NOT actually a single defined tract.  Ascending Tracts Carrying Unconscious Sensory Information There is one defined somatic afferent (sensory) tract carrying unconscious sensation: Spinocerebellar Pathway/Tracts: Unconscious proprioception – the sense of where your limbs/body are in space. This is “used” by interneurons in the cerebellum to modify the activity of motor neurons. These fibres usually do NOT decussate, instead ascending on the ipsilateral side of the spinal cord and entering the cerebellum via the caudal cerebellar peduncle. These fibres have a relatively high susceptibility to injury due to heavy myelination and location in spinal cord. Spinocerebellar Pathway Proprioception – Clinical Exam Knacking > dorsal spine & Spinocerebellum issue - http://www.youtube.com/watch?v=IXpGX6xhJdM  Fig 6-6 Descending Tracts: General Features Carry the motor fibres that control "somatic" muscle movement in the body. As with sensory pathways, motor impulses travels in specific tracts found in white matter. Similarly, the pathways are named based on origin and destination - there are three major and two minor pathways of significance (for domestic species). A major portion of the clinical neurologic examination involves the examination of responses mediated by the motor tracts (in veterinary medicine), although the sensory pathways must also be intact in order for the test to be 'normal’ so we often evaluate both sensory and motor together.  Fig 6-6 Descending (Motor) Tracts Three major descending pathways and two minor (typically considered less important in animals other than primates) pathways are commonly described in veterinary medicine. These pathways have 2-3 neurons in a series which start at specific nuclei in the brain and end at a specific spinal level where they synapse on a lower motor neuron (details in subsequent slides). Moderately myelinated, so susceptibility to injury falls between proprioceptive pathways (very sensitive) and pain pathways (least sensitive).  Fig 6-6 Descending (Motor) Tracts Major Tracts Rubrospinal Tract - Red Nucleus to spinal cord, decussates in midbrain. Probably the most important tract in domestic species. Reticulospinal Tract - Reticular Formation (in medulla) to spinal cord. Involved in balance and posture. Mostly ipsilateral, with some decussation to the contralateral side. Vestibulospinal Tract - Vestibular Nuclei to spinal cord. Involved in synergy of muscle movements, equilibrium, and balance. Entirely ipsilateral.  Fig 6-6 Descending (Motor) Tracts Minor Tracts: Corticospinal Tract - Cortex to spinal cord, similar to Rubrospinal Tract, but originates in the cortex. Sometimes called a “pyramidal” tract. Tectospinal Tract – like the corticospinal tract but to cervical cord segments only, responsible for head movements in response to auditory/visual stimuli.  cordFig 6-6 Descending (Motor) Tracts inspired function > - Motor tracts contain UPPER MOTOR NEURONS that initiate muscle contraction and movement after synapsing on LOWER MOTOR NEURONS that leave the spinal cord at each level to innervate muscle. Upper Motor Neuron (UMN) - Refers to all the neurons in a motor tract, except the final neuron which leaves the spinal cord and directly innervates a muscle fibre. UMNs are entirely in the CNS (brain and spinal cord). UMNs are in tracts. Lower Motor Neuron (LMN) – Refers to the final neuron in a motor pathway, which exits the spinal cord and travels, via the ventral root, to a target muscle. LMNs start in the CNS and terminate in the PNS. UMNs from multiple different motor tracts can all synapse on a single LMN, which carries impulses to a muscle.  Descending (Motor) Tracts: Upper and Lower Motor Neurons UMNs travel from the brain in different tracts then synapse on LMNs which leave the spinal cord and innervate muscle. UMNs can ONLY be injured if the spinal cord is injured. ↳ S brain y LMNs can be injured if the spinal cord OR the peripheral nerve - in which they travel is injured. Spinal Cord: Descending (Motor) Tracts nusa startsinrd ↑ Rubrospinal Tract: Major descending pathway in animals. Responsible for voluntary muscle movement. Spinal Cord: Descending (Motor) Tracts Corticospinal Tract(s): Minor descending pathway in animals (important in humans and other primates) ↳ fine muscle movement Spinal Cord: Descending (Motor) Tracts in brain stem start ↑ Reticulospinal and Vestibulospinal Tracts Responsible for involuntary movements controlling posture, balance etc. Often contain inhibitory neurons to prevent excessive responses to stimuli etc.  Motor and Sensory Pathway Integration: Complexity! Through complicated feedback from sensory pathways, motor impulses are constantly fine-tuned both consciously and subconsciously. The cerebellum and vestibular apparatus provide both excitatory and inhibitory APs through the vestibulospinal and reticulospinal pathways that adjust posture and balance subconsciously that modifies the primary motor impulse in the rubrospinal and corticospinal tracts. FOR BACKGROUND ONLY UMNs, LMNs, Brachial and Lumbosacral Plexus’  Features of the Spinal Cord and Peripheral Nerves Spinal nerves leave the spinal cord on each side at each segment. However, most peripheral nerve lesions we see are in specific “named” nerves (eg. Radial Nerve, Femoral Nerve etc.) that travel in the forelimbs and hindlimbs. What is the relationship between these named nerves and the different spinal nerves and segments?  Refresher: Spinal Cord Anatomy Cervical (cervicothoracic) enlargement: supplies forelimbs (Segments C6, C7, C8, T1, (T2)) – Forelimb reflexes, Forelimb LMNs Lumbosacral enlargement: supplies hindlimbs (Segments L4, L5, L6, L7, S1, (S2) – Hindlimb reflexes, Hindlimb LMNs vanat.cvm.umn.edu  RS forelimbs one on one on LS windlimbs one on RS on LS Fig 6-6 one ↑ ↑ ↑ ↑ The Brachial Plexus and Lumbosacral Plexus A pattern of organization of the peripheral nerves that originate from spinal cord levels C6 to T2 (Brachial Plexus) and L4 to S2 (Lumbosacral Plexus) merga Spinal nerves coalesce in a specific manner to allow innervation (sensory and motor) of specific regions/muscles by nerves from more than one spinal level. The spinal nerves from two to four different (but adjacent) spinal levels give rise to specific peripheral nerves, e.g. the Radial Nerve is composed of C7, C8, T1 and the Sciatic Nerve comprises L6, L7, S1. A single spinal segment may provide axons for more than one peripheral nerve, (e.g. the subscapular and median nerves have roots in C8).  The Brachial Plexus and Lumbosacral Plexus (BILATERAL!) Bilateral: Brachial plexus to is here ↑ & -Whiches - which Si ↑ to T2 nerve ↑ T2 ↑ ↑ cercothoracI ement a brachial plexus  Relationships Between “Enlargements” and “Plexuses” Lumbosacral Lumbosacral Plexus Cervicothoracic Brachial Plexus Enlargement Enlargement  Upper vs. Lower motor neuron damage proprioception = sensory neuron motorrasu, ans How do we clinically distinguish between upper and lower motor neuron damage (UMN vs. LMN damage)?  Upper vs. Lower motor neuron damage 1. Evaluate the “tone” in the muscles of the affected limb. LMN damage leads to DECREASED tone (flaccid paresis/paralysis) and, after a week or so, NEUROGENIC ATROPHY. UMN damage leads to INCREASED tone (spastic paresis/paralysis). Disuse atrophy develops over a longer time period as the animal no longer uses the limb effectively. Increased tone (spastic) Disuse atrophy X Loss of tone (flaccid) Neurogenic atrophy X  Upper vs. Lower motor neuron damage ↓ tone neurogenic atrophy s signs of LMN damage > - , diminished reflex 2. Evaluate the reflexes (Remember, LMNs are a key part of the reflex arc). With LMN damage reflex will be: 1) exaggerated 2) normal 3) diminished  Upper vs. Lower motor neuron damage UMN damage - exaggerate - normal reflex , ↑ tone muscle 2. Evaluate the reflexes (Remember, LMNs are a key part of the reflex arc). With UMN damage reflex will be: 1) exaggerated 2) normal 3) diminished Loss of inhibitory inputs by UMN in descending tracts. How do we use our knowledge of spinal cord anatomy, tracts, reflexes and plexuses to “Localize a Lesion”?  Algorithm for Localizing a Lesion in Spinal Cord vs Peripheral Nervous System 1. Does the animal have a neurologic lesion? Neurologic exam reveals decrease or loss of function in one or more limbs: proprioceptive abnormalities, abnormalities in gait (ataxia, positioning abnormalities), weakness (paresis/paralysis), decrease or absence in pain sensation. 2. What limb(s) are affected? 1 limb only – likely a peripheral nerve problem. 2 or 4 limbs affected (bilateral) – likely in the spinal cord. 3. Is there ataxia? Presence of ataxia supports the conclusion that lesion is likely in the spinal cord (shows that proprioceptive tracts are damaged). 4. What reflexes are decreased? If lesion is in the spinal cord at the cervicothoracic enlargement, reflexes in the forelimb will be DECREASED (ALSO: tracts that pass through the area to the hindlimbs will be affected). If lesion is in lumbosacral enlargement, hindlimb reflexes will be DECREASED. If lesion is between C1 and C5 (audio is incorrect) or T3 and L3 NO decrease in reflexes will be observed in the limbs. Algorithm for Localizing a Lesion in Spinal Cord vs Peripheral Nervous System 5. Consider again what limbs are affected? Hindlimbs ONLY affected – Lesion must be caudal to T2 - This is where the last spinal nerves for the forelimb enter/exit, so the lesion doesn’t affect the motor or sensory fibres above that level and the forelimbs appear normal. Forelimbs AND Hindlimbs affected (Note: the severity and signs don’t need to be the same in fore and hind, only whether or not they have ANY neurologic signs) – Lesion must be above T2 because it is affecting the sensory and motor tracts pathways in ALL legs. 6. Consider #4 and #5 together: If hind limbs only are affected AND hindlimb reflexes are affected, lesion is L4 – S2. If hind limbs only are affected and NO reflexes are decreased, lesion is T3 – L3. If forelimbs and hind limbs are affected AND forelimb reflexes are decreased, lesion is C6 – T2. If forelimbs and hind limbs are affected and NO reflexes are decreased, lesion is C1 – C5.  Summary: signs when lesions are present in different spinal regions (Note: Signs will be bilateral, but may differ in severity). C1 – C5: Ataxia, proprioceptive decrease in ALL 4 limbs (tracts affected). MAY see paresis/paralysis (if motor tracts affected) and decreased pain (if pain tracts affected). Normal to increased reflexes in all 4 limbs (UMN affected, reflex arcs/LMN for limbs NOT affected) C6 – T2: Ataxia, proprioceptive decrease in ALL 4 limbs (effects on tracts, LMN, reflex arcs). MAY see paresis/paralysis (if motor tracts or LMN affected) and decreased pain (if pain tracts affected). Decreased reflexes in forelimbs (LMN affected), normal to increased reflexes in hindlimbs (UMN affected). T3 – L3: Ataxia, proprioceptive decrease in hindlimbs only (effects on tracts). MAY see paresis/paralysis (if motor tracts affected) and decreased pain (if pain tracts affected). Normal reflexes in forelimbs, normal to increased reflexes in hindlimbs (UMN affected). L4 – S1: Ataxia, proprioceptive decrease in hindlimbs only (effects on tracts, LMN, reflex arcs). MAY see paresis/paralysis (if motor tracts or LMN affected) and decreased pain (if pain fibres/tracts affected). Decreased reflexes in hindlimbs ONLY (LMN and reflex arcs affected). Normal reflexes in forelimbs. vanat.cvm.umn.edu Where is the “Lesion”? http://www.youtube.com/watch?v=S8piNrhIGic 1. Does this animal have a neurologic lesion? YES – abnormal gait/ataxia. Neurologic exam would reveal proprioceptive abnormalities in all four limbs with some weakness. Pain is normal. 2. What limb(s) are affected? All 4 limbs – lesion is in spinal cord. Must be above T2. 3. Is there ataxia? YES - Confirms that lesion is likely in the spinal cord (proprioceptive tracts damaged – only seen in CNS disease). 4. What reflexes are decreased? Neurologic exam would reveal mild exaggeration in reflexes in ALL 4 limbs with NO decreased reflexes. 5. and 6. – Because the lesion is in all 4 limbs, with no decreased reflexes, lesion must be between C1 and C5 in the spinal cord. Proprioceptive pathways are affected, leading to ataxia. Some evidence of weakness (stumbling, delayed movement) and exaggerated reflexes suggests motor pathways (UMN) are affected. Pain sensation intact. This is a mild to moderate severity lesion as all signs are mild but multiple pathways are affected.  Radiograph: Cervical “Lesion” t too wobblers-growL quicklynormal becomes > - spinef t horses& great danes endotracheal - tube -shoulder cal.vet.upenn.edu/projects/saortho/chapter_63/63mast.htm single limb- Where is the Lesion? chial plans peripheral specefic nerve nerve in RF injury ↓ ↓ not in spinal cord radial newve ? ↓ ? injurysuckling brachial plexus avoltion = ↳issue in nerves in brachial plexus - All nerves in brachial plexus effected ↳ no reflexes http://www.youtube.com/watch?v=Fzvzg_Pq_NQ Reflexes and Motor Pathways http://www.youtube.com/watch?v=NFqFABsIa7Q  Neuromuscular Physiology Myostatin mutants in cattle and dogs  Neuromuscular Physiology Skeletal (Voluntary) Muscle My(o-) from Greek mys = Muscle Sarco- from Greek sarkos = Flesh Myocyte: Muscle cell with single nucleus Myofibre: Multinucleated muscle cell Sarcolemma: Myofibre plasma membrane Sarcoplasm: Myofibre cytoplasm S. Yamashiro, U of G.  Neuromuscular Physiology Skeletal (Voluntary) Muscle - Made of cylindrical, multi- nucleated myofibres - Each fibre spans the length of the muscle - Most are attached to the skeleton across joints à contraction causes gross movement - Microscopically, fibres have a striped or “striated” appearance, hence also called striated muscle - S. Yamashiro, U Guelph  Neuromuscular Physiology - Each myofibre has one neuromuscular junction (NMJ)  Neuromuscular Transmission 1. Sodium influx 2. Depolarization 3. Release of Ca2+ 4. Interaction of actin and myosin 5. Shortening of the sarcomere 6. Na+ channels close and Na+ pumped out 7. Repolarization 8. Ca2+ channels close and Ca2+ pumped into SR 9. Sarcomere relaxes  Neuromuscular Physiology Skeletal Myofibres - Contain myofibrils, which are bundles of myofilaments, made of the contractile proteins actin & myosin - Actin & myosin arranged in regular pattern between attachment plates called Z-lines or Z- disks - Area between two Z- disks called a sarcomere  Neuromuscular Physiology Electron microscopic image of a sarcomere in one myofibril - A Young Titin filament  Neuromuscular Physiology Skeletal Myofibres Contain myofibrils, which are bundles of myofilaments, made of the contractile proteins actin & myosin - Region between two “Z” lines (or disks) is a sarcomere T-tubules wrap around each myofibril at the Z- disk; Sarcoplasmic reticulum (SR) (containing Ca2+) stretches between T- tubules along surface of myofibril  Neuromuscular Physiology Sarcomere - The contractile unit of skeletal muscle - Actin (thin filaments) anchored at Z-line - Myosin (thick filaments) located between actin - A Young  Neuromuscular Physiology Myosin - Each myosin protein is a homodimer: 2 molecules coil together to form a tail region with 2 head groups - Head groups are hinged - Many myosin molecules combine to form a thick filament  Neuromuscular Physiology Actin Thin filaments are composed of: - actin - troponin - tropomyosin “F-actin” (filamentous) consists of chains of globular actin (G-actin) G-actin Actin has binding sites for myosin; they are hidden by the tropomyosin strand. Troponin has high affinity for Ca2+. A troponin molecule is bound to each tropomyosin strand.  Neuromuscular Physiology Excitation- contraction coupling AP in motor neuron causes voltage- gated Ca2+ channels in axon terminus to open à triggers NT vesicle fusion à NT released into cleft Note: Motor End Plate (MEP) is part of NMJ  Neuromuscular Physiology Excitation- contraction coupling NT is ACh - Binds to nicotinic AChRs in specialized region of muscle membrane at motor end plate (MEP) - AChRs open à Na+ enters cell à local depolarization at MEP Note: Motor End Plate (MEP) is part of NMJ  Neuromuscular Physiology Excitation- contraction coupling Y MEP depolarization triggers AP in surrounding sarcolemma à Spreads into T-tubules How does depolarization of T-tubules cause muscle to contract? Two Excellent Videos Explaining Muscle Excitation and Contraction Excitation-Contraction Coupling: https://www.youtube.com/watch?v=LlgaziPCFU0 “Rachet” or Sliding-Filament Contraction: https://www.youtube.com/watch?v=cf-sjB3WpRo  Neuromuscular Physiology Excitation- contraction coupling Voltage-gated Ca2+ channels (Cav1.1) in T-tubules sense depolarization - 4 of these channels tug on the “foot” of a different Ca2+ channel, the ryanodine receptor (RYR), which is in the SR membrane à RYR opens, Ca2+ enters sarcoplasm from SR  Neuromuscular Physiology Excitation- contraction coupling In other words, the voltage sensor in one Ca2+ channel (Cav1.1) opens a different Ca2+ channel (RYR)  Neuromuscular Physiology Actin When Ca2+ is released from SR, it binds troponin It affinity for cast à Causes tropomyosin strand to move à Reveals myosin binding G-actin sites on actin à Cross-bridge forms (between actin and myosin) à Myosin head group tilts à Contraction  Neuromuscular Physiology “Ratchet” theory of contraction ATPase in myosin head group cleaves ATP à Extends headgroup, which binds to actin à Binding is followed by tilting of headgroup, which slides actin about 5-10 nm à New ATP molecule binds myosin head group, which releases actin à ATP then cleaved to tilt head group again à Cycle repeated as long as Ca2+ levels are high  FYI ONLY!! Muscle Contraction is Associated with Cyclical Association and Disassociation of Actin and Myosin ATP is reformed and cycle can be repeated ATP promotes detachment of myosin Change in angle of Hydrolysis of myosin head ATP allows shortens movement of sarcomeres myosin head Calcium allows myosin to bind actin  Energy Generation for Muscle Contraction a cytopla in X AMP > - phosphorylates creative (2ADP à ATP + AMP) ADP CK = Creatine kinase Sources of ATP Over Time muscle to store energy allows in another form X Phospho-creatinine contribute don't slower , muscle rapidcontraction t X Heterogeneity of Skeletal Muscle White or Fast Twitch – Short contraction times – larger in size and more extensive sarcoplasmic reticulum – Adapted for anaerobic metabolism Red or Slow Twitch – Long contraction times – Smaller in size with less extensive sarcoplasmic reticulum – Adapted for aerobic metabolism  Biochemical Differences in Muscle FYI ONLY!  Neuromuscular Physiology Removal of Calcium - Calcium ATPases or “pumps” reset the intracellular calcium level by moving Ca2+ out of the cell or back into the sarcoplasmic reticulum. - Cell surface pump is called the plasma membrane calcium ATPase (PMCA) S - Sarcoplasmic reticulum pump is called sarcoplasmic/ endoplasmic reticulum ATPase (SERCA) · ↓ FEBS Letters redistributes cat when not contracting  Smooth Muscle Smooth (Involuntary) Muscle (a.k.a. single unit smooth m.) Controlled by nervous stimulation Controlled mainly by local stimuli, (ACh or NE) with some nervous regulation - ciliary muscles - cells connected by gap junctions - piloerector muscles - may have spontaneous slow - large blood vessel tone waves that trigger APs - APs or decremental depols may cause contraction  Smooth Muscle Skeletal Muscle Smooth Muscle APs in visceral smooth muscle are slower than in skeletal muscle and persist longer - “Graded” depolarizations can cause contraction, APs cause more forceful contraction