VBMS 212 Neurology Quiz 2

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PERIPHERAL SENSORY FUNCTION: Enteroception
- nociception
- deep receptors
- superficial receptors

Proprioception
- conscious
- unconscious
NOCICEPTORS: Pain and Noxious Stimuli

Respond to potentially tissue damaging stimuli
- Thermal
- Mechanical
- Inflamatory

Bare Nerve Endings

Cell Body in Dorsal Root or Cranial Ganglia

Primary Afferent axons are small with little or no myelination tf slow

High Threshold ie not sensitive
THREE ACTIONS OF NOCICEPTORS: Direct Activation via cold or heat, Mechanical Damage, Chemical Damage

Damage of surrounding tissue causes release of cellular contents (ie Histamine, Bradykinins etc) generating further stimulation

Once activated the receptor RELEASES Glutamate and Substance P, amplifiying inflamation and vasodilation
MINIMUM NUMBER OF NEURONS IN ENTEROCEPTION PATHWAYS: 3
FOUR ENTEROCEPTION PATHWAYS KNOWN IN CATS AND DOGS AND PRESUMED IN OTHER VETERINARY SPECIES: Dorsal Funicular

Spinothalamic

Spinoreticular

Spinocervical
FUNKY FACTS ABOUT DORSAL FUNICULAR PATHWAY: aka Lemniscal

Peripheral Sensory Enteroception

3 Neurons

Primary Sensory Afferents DIRECTLY enter dorsal funiculus via dorsal root

Fasciculus Gracilis carries axons from Caudal regions and Hind Limbs

Fasiculus Cuneatus carries axons from Cranial regions and Fore Limbs

Primary sensory afferents synapse on Nuclei Gracilus and Cuneatus in caudal portion of Medulla

Axons from Nuclei Gracilus and Cuneatus DECUSSATE and travel in the Contra Lateral MEDIAL LEMNISUCUS where they synapse on nuclei in the Rostral thalamus

Axons from the nuclei in the thalamus travel to the SOMATO SENSORY CORTEX
FASICULUS GRACILUS: Medial Portion of Dorsal Funiculus

Carries primary sensory afferents from caudal regions and hind limbs for
- enteroception
- Conscious Proprioception
FASICULUS CUNEATUS: Lateral Portion of Dorsal Funiculus

Carries primary sensory afferents from cranial regions and fore limbs for
- enteroception
- Conscious Proprioception
SOMATOTOPIC ARRANGEMENT: Adjacent areas of the body are represented by axons which run adjacent to each other
SIZZILING SENSATIONS ABOUT SPINOTHALAMIC PATHWAY: Peripheral Sensory Enteroception

3 Neurons

Primary sensory afferents enter dorsal horn via dorsal root and SYNAPSE on nuclei of afferent interneurons

Axons of afferent interneurons cross Grey Commissure and travel in the CONTA LATERAL LATERAL FUNICULUS

Interneurons synapse in the Thalamus

Axons from the nuclei in the thalamus travel to the SOMATO SENSORY CORTEX
ROUSING REVELATIONS ABOUT SPINORETICULAR PATHWAY: Peripheral Sensory Enteroception

3 OR 4 Neurons

Primary sensory afferents enter dorsal horn via dorsal root and SYNAPSE on nuclei of afferent interneurons

Axons of afferent interneurons cross Grey Commissure and travel in the CONTA LATERAL LATERAL FUNICULUS

Interneurons synapse in the Thalamus AND ALSO have COLATERAL neurons which synapse in various regions of brain stem.

Axons from neurons (the 4th neurons) in the various regions in the brain stem synapse in the thalamus

Axons from the nuclei in the thalamus travel to the SOMATO SENSORY CORTEX
CURIOSITIES ABOUT SPINOCERVICAL PATHWAY: Peripheral Sensory Enteroception

4 OR 5 Neurons

Primary sensory afferents enter dorsal horn via dorsal root and SYNAPSE on nuclei of afferent interneurons

Axons of afferent interneurons travel in the IPSO LATERAL LATERAL FUNICULUS

Axons from the distal afferent interneurons synapse on LATERAL CERVICAL NUCLEI in the C1 - C2 spinal segments.

Axons from the LATERAL CERVICAL NUCLEI decussate in the MEDIAL LEMNISCUS and then travel contralaterally to synapse in the Thalamus AND ALSO have COLATERAL neurons which synapse in various regions of brain stem.

Axons from neurons (the 5th neurons) in the various regions in the brain stem synapse in the thalamus

Axons from the nuclei in the thalamus travel to the SOMATO SENSORY CORTEX
NASTY NOTIONS NOCICEPTION PATHWAY: Peripheral Sensory Enteroception

Minimum 3 Neurons

Primary sensory afferents enter dorsal horn via dorsal root and SYNAPSE on nuclei of afferent interneurons

Sensory Afferents travel via
- Spinothalamic Pathway and Bilateral (decusation) Pathway

Multiple multisynaptic bilateral pathways are SLOWER but more ROBUST tf absence of response to Deep Pain Stimulus indicates a severe lesion.
SOMATOSENSORY CORTEX: Receives Enteroceptic Sensory Afferents

Located in ventral rostral region of cerebral cortex

Required for
- conscious perception of pain
- localization of pain
- pain related learning
NOCICEPTION BRAIN STEM: Nociceptive information reaching Pons or Medulla is important for changing STATE OF AROUSAL
NOCICEPTION MID BRAIN: Nociceptive information that reaches midbrain is transferred to structures of LIMBIC SYSTEM that are responsible for EMOTIONAL response to pain
NOCICEPTION HYPOTHALAMUS: Cardiovascular and neural hormonal responses to pain
NOCICEPTION SPINAL COLUMN - DORSAL HORN: Nociception afferent interneuron receives:

- stimulation from nociceptor primary afferent both directly and via inhibition of inhibitory interneurons
- inhibition and stimulation from non nociceptor primary sensory afferents
- inhibition and stimulation from descending brain neurons
- tf high level of control
GATE THEORY OF PAIN: Gating of nonnociceptive inputs blocks transmission of nociceptive transmission to brain at level of dorsal horn neurons

ie pressure sensing neurons can have a net stimulatory effect on nociception inhibitory neurons in short term tf rub to alleviate pain

OR

long term noxious stimulation (ie inflamation) creates hypersensitivity in Dorsal Horn Nociceptor Afferent Interneuron. As a result low levels of stimulation from non nociceptor primary sensory afferents result in net stimulation of nociception afferents tf sensitivity to pressure around wound
NEUROPATHIC PAIN: No source in periphery

Dorsal Horn:
- spontaneously hyperexcited
- or remains hyperexcited after stimulation

Difficult to control

Common in spinal cord injury

tf, in addition to general aneshtetics, use local anesthetics in dorsal horn when AMPUTATING
MIDBRAIN MODULATION OF PAIN: Periaquaductal Grey Matter
- area around mesodermal aqueduct

Neurons in Periaqueductal Grey Matter INHIBIT activity in DORSAL HORN neurons

Responsive to OPTIATES

Stimulated by intense activities ie fighting
TWO OTHER AREAS OF PAIN MODULATION: Synapses in Pons and Medulla

Dorsal Horn Neurons
- receptors for Opiods and NE inhibit tf use opiods or alpha agonists (xylazine) for epidurals
PROPRIOCEPTION: Spatial awareness of musculoskeletal system

sense of location and motion of all body segements

Conscious - pathways end in Cerebral Cortex

Unconscious - pathways end in Cerebellum
PROPRIOCEPTIVE RECPTORS THREE LITTLE PIGGIES: Muscle Spindles
- length of muscles
- speed of change of muscle length
- Ia axons largest and fastest

Golgi Tendon Organ
- force in muscle
- Ib axons large but not largest diameter

Stretch Receptors
- joint Capsules
- skin over joints
- αβ axons mid size diameter

Sensor afferents that conduct information from prorioception receptors are amoungst largest in body
CONSCIOUS PROPRIOCEPTION PATHWAY: Primary sensory afferents DIRECTLY enter dorsal funiculus

Caudal and hind limb afferents travel in Ipsolateral Funiculus Gracilis

Cranial and fore limb afferents travel in Ipsolateral Funiculus Cuneatus

Primary sensory afferents synapse on nuclei gracili and cuneati in Caudal Medulla

Axons from nuclei Gracili and Cuneati decussate and travel in Contralateral Medial Lemniscus and synapse in Thalamus.

Axons from nuclei in thalamus travel to Somatosensory Cortex
UNCONSCIOUS PROPRIOCEPTION PATHWAY CAUDAL AND HINDLIMBS: Primary Sensory afferents enter the dorsal horn and synapse in the dorsal grey columns

Axons from nuclei in the dorsal grey columns then ascend via two tracts:

DORSAL SPINOCEREBELLAR TRACT
- Ipsolateral in the Dorsal Spinocerebellar Tract of the Lateral Funiculus to the Cerebellum via the Caudal Cerebellar Peduncle.

VENTRAL SPINOCEREBELLAR TRACT
- Contralateral in the Ventral Spinocerebellar Tract of the (contralateral) Lateral Funiculus to the Cerebellum via the Rostral Cerebellar Peduncle.
UNCONSCIOUS PROPRIOCEPTION PATHWAY CRANIAL AND HINDLIMBS: Primary Sensory afferents enter the dorsal horn and synapse AS WELL AS BRANCH in the dorsal grey columns

CUNEOCEREBELLAR TRACT
- a branch of the primary sensory afferent directly enters the lateral most part of the Ipsolateral Funiculus Cuneatus and synapse in the LATERAL CUNEATE NUCLEUS in the medulla. Axons from neurons in the Lateral Cuneate Nucleus decussate and travel through the Caudal Cerebellar Peduncle to the Cerebellum.

ROSTRAL SPINOCEREBELLAR TRACT
- axons from nuclei in the dorsal grey columns then ascend ipsolateral in the Rostral Spinocerebellar Tract of the Lateral Funiculus to the Cerebellum.
BRAIN BASICS TELENCEPHALON DIENCEPHALON MESENCEPHALON METENCEPHALON MYELENCEPHALON: Cerebrum
- cerebral cortex
- subcortical structures
- Lateral Ventricles

The Thalamus Family
- epithalamus
- thalamus
- hypothalamus
- third ventricle

Mesencephalon
- mesencephallic aqueduct

Metencephalon
- pons
- cerebellum
- fourth ventricle

Medulla
- fourth ventricle as well
MIDBRAIN: Cerebral Peduncles
- ventral portion
- rostral caudal fibres
- axons of Upper Motor Neurons
- axons of Lower Motor Neurons

Tementum

Tectum
- Dorsally Located Colliculi
- Rostral Colliculi coordination of Visual Reflexes
- Caudal Colliculi coordination of auditory reflexes

Cranial Nerve III
- Oculomotor Nerve
- lower motor neurons
- enervates Extrinsic Eye Muscles

Cranial Nerve IV
- Trochlear Nerve
- also enervates extrinsic eye muscles
- thin
DIENCEPHALON: Epithalamus (Pineal Gland)

Hypothalamus

Thalamus

Cranial Nerve II
- Optic Nerve
PONS: Fibres of Pons
- lateral structure contains fibres which travel to cerebellum

Cranial Nerve V
- Trigeminal Nerve
- lower motor neurons
- enervate muscles of mastication tf BIG

Cranial Nerve VI
- Abducens Nerve
- Lower Motor Neurons to extrinsic muscles of eye
MEDULLA: Nuclei Cuneatus

Nuclei Gracilis

Pyramids
- contain Upper Motor Neurons ONLY

Cranial Nerve VII
- Facial Nerve
- Lower Motor Neurons to facial muscles
- efferents to salivary and lacrimal glands
- afferents for taste
- Rostral Medulla

Cranial Nerve VIII
- Vestibulocochlear Nerve
- afferents from internal ear

Cranial Nerve IX
- Glossopharyngeal
- Efferents/Afferents Pharynx
- Afferents Taste
- Autonomic Salivary Glands

Cranial Nerve X
- Vagus
- Efferent/Afferents larynx, pharynx and viscera

Cranial Nerve XII
- Hypoglossal
- Lower Motor Neurons
- enervates tongue
FOUR CRANIAL NERVES THAT HAVE CLINICAL RELEVANCE: III - Midbrain

V - Pons

VII - Rostral Medulla

XII - Caudal Medulla

Clincially interesting for signs of Lower Motor Neuron Damage
CERVICAL SPINAL CORD: Cranial Nerve XI
- Spinal Accessory Nerve
- Lower Motor Neurons
- enervates certain neck and thoracic limb muscles
RETICULAR FORMATION: All the matter of the brain stem less the muclei associated with cranial nerves

Basically the brain stem is a big mess of neurons with extensive and complicated connections
FOUR FUNCTIONS OF RETICULAR FORMATION: Behavioral Arousal

Motor Control

Modulation of Pain Sensation

Coordination of Some Autonomic Functions
- Respiratory Control
- Cardiovascular Control
- Vomition
RETICULAR FORMATION BEHAVIOURAL AROUSAL: Ascending Reticular Activating System
- required for maintenance of CONSCIOUSNESS ie powers up cerebral cortex
- lesions in brain stem have potential to alter level of conciousness

All inputs of cranial nerves I, II, V and VIII synapse in reticular formation

Neurons in reticular formation synapse int the Thalamus which sends many neurons throughout the cerebral cortex resulting in DIFFUSE DISTRIBUTION
RETICULAR FORMATION MOTOR CONTROL: Some Upper Motor Neurons are present in Reticular Formation
RETICULAR FORMATION MODULATION OF PAIN SENSATION: Periaquaductal Grey matter resides in Reticular Formation

Neurons with opiate receptors synapse in other regions of Reticular Formation. These neurons send axons to spinal cord which inhibit Dorsal Horn Neurons associated with pain
RETICULAR FORMATION RESPIRATORY CONTROL: Maintains normal levels of CO2 and O2 via alveolar ventalation
- respiration rate
- respiration depth

Inputs
- CO2, pH, O2 Receptors
Outputs
- motor neurons that enervate respiratory muscles

PRE BOTZINGER COMPLEX
- source of respiratory rhythm
- located in MEDULLA

DORSAL RESPIRATORY GROUP
- enervates Inspiratory neurons ONLY
- located in Dorsal MEDULLA

VENTRAL RESPIRATORY GROUP
- enervates inspriatory and expiratory neurons
- located in VENTRAL MEDULLA

PONTINE RESPIRATORY GROUP
- acts on Dorsal Respiratory Group to inhibit inspiration
- located in PONS

Voluntary Control Centre
- located in SOMATOSENSORY CORTEX

Mechanical Regulation
- Stretch Receptors in lung inhibit Dorsal Respiratory Centre via Vagus nerve
RESPIRATORY CENTRE LESIONS: Respiratory muscles (abdominal, intercostals and diaphragm) are enervated by Phrenic Nerve tf Spinal Segments C5, C6, C7

Lesion in Pons but not Medulla produces long slow inspiration and low respiration rate

Lesion in Voluntary Control Centre will not stop breathing

Lesion in Medulla will produce loss of rhythmicity and increase or decrease of rate and depth of respiration

Lesion in upper spinal cord will stop breathing

Chemo and Barrow receptors synapse in the Dorsal Respiratory Group
- Aortic Body Receptors are enervated by Cranial Nerve IX
- Carotid Body Receptors are enervated by Cranial Nerve X

Lesion in Vagus stops inhibition of Dorsal Respiratory Centre tf long inspiration and reduction of respiration rate
RESPIRATORY CENTRE CHEMORECEPTOR EFFECTS: CO2-
- has most significant effect
- receptors in CNS detect CO2 changes via changes in in H+ because of BBB
- H+ levels in CSF follow H+ levels in blood because low protein in CFS produces low buffering capacity

O2
- response only when pO2 < 60 mmHg

Animals under anesthesia have reduced response to changes in CO2 because receptors and respiratory centres are suppressed
CARDIOVASCULAR CENTRE: Located in Reticular Centre of Medulla
- Pressor Centre
- Depressor Centre
VOMITION CENTRE 5 SENSORY PATHS: Located in Dorsal Medulla

Receives Sensory Afferents from:
- abdominal vagus nerve
- cerebral cortex
- vestibular nuclei
- olfactory regions of brain
- CHEMORECEPTOR TRIGGER ZONE
(located in medulla near vomition centre)

Blood Brain Barrier is compromised near chemorecptor trigger zone
- tf sensitive to blood glc and drugs
- apomophine, morphine stimulate
- metaelopramide inhibits

Sufficient stimulation from sensory afferents causes vomition centre to initiate a coordinated series of events resulting in regurgitation
THALAMUS FIVE FUNCTIONAL SOUND BITES: Composed of a large number of Nuclei

Acts as a processing and relay system for information going up to the cerebral cortex from spinal system and brain stem

Much of the information from the cerebral cortex synapses in thalamus and is relayed to other parts of brain

Diffusely distributes information received from Ascending Reticular Activating System to Cerebral Cortex

Role in reception of pain
- animals without cerebral cortex still perceive pain in a general way
HYPOTHALAMUS 6 FUNCITONS: Coordination and Regulation of Automomic System

Neuroendocrine Regulation via Adenohypophysis

Coordinates expression of STRONG EMOTIONS ie RAGE

Regulation of Temperature

Regulation of Feeding

Regulation of Circadian Rhythms
TEMPERATURE REGULATION RECEPTORS: - Central located in the PREOPTIC AREA which is in the rostral most part of hypothalamus
- Preoptic area is just rostral to the optic chiasm tf pituitary tumors can affect vision
- Central recepetors are more sensitive to increases in temperature

- Peripheral in skin and visceral
- peripheral receptors are more sensitive to decreases in temperature

- both central and peripheral receptors respond to increases or decreases in temperature
TEMPERATURE REGULATION COORDINATING CENTRES HOW MANY AND WHERE?: Heat Loss Centre
- Rostral Hypthalamus
- stimulation produces loss of heat
- vasodilation, sweating, shade seeking
- lesions produce chronic hyperthermia

Heat Retention Centre
- Caudal Hypthalamus
- stimulation produces retention of heat
- vasoconstriction, piloerection, shivering, shelter seeking
- chronic stimualtion of cold receptors will result in release of thyroid hormones via release of TSH. Produces increased cellular metabolism over several weeks
- lesions not noticeable until animal exposed to cold, results in chronic hypothermia

Deviation from temperature setpoint results in stimulation/suppresion of both centres tf responses driven by net output of both centres

Periphery may have local response which is independent of central centres
PYREXIA: aka Fever

Increase in body termperature above normal

Pyrogens released in pathological conditions (LPS, IL-1 etc)
- increase firing rate of cold sensitive neurons in pre optic area
- same effect as cooling hypothalamus

Halothane and Isoflurane reduce senstivity of temperature sensitive neurons
- tf thermoregulation operates over a wider termperature zone
TEMPERATURE REGULATION INHALATION ANESTHETICS: Holothane and Isoflurane reduce senstivity of termperature sensitive neurons
- tf thermoregulation operates over a wider termperature zone
APPETITE REGULATION CENTRES HORMONES: FEEDING CENTRE
- lateral regions of middle hypothalamus
- stimulation produces eating or searching for food
- bilateral lesions result in starvation (note will eat if food placed in mouth)

SATIETY CENTRE
- ventral medial region of middle hypothalamus
- stimulation stops eating
- chronic stimulation results in starvation
- bilateral lesions result in continuous eating and EXTREMELY AGGRESSIVE BEHAVIOUR
- tf satiety centre inhibits aggressive behaviour

Inputs to centres are received from:
- Cerebral Cortex conscious control
- olfactory system

Outputs of both centres go to Pons and Medulla which regulate the mechanics of eating

Hormonal Influences

- GHRELIN is released from stomach prior to feeding.
- Activity in hypothalus is likely in Feeding Centre

- LEPTIN is released from Adipocytes after feeding.
- Activity in hypothalamus is likely in Satiety Centre
CENTRE: Area of CNS that is FUNCTIONALLY DEFINED by electrical sitmualtion and lesioning

May contain axons or cell bodies tf response of centre may be due to stimulation of either
REGULATION OF CIRCADIAN RHYTHM: Intrinsic Pacemaker (major of several) is located in SUPRACHIASMATIC NUCLEUS
- nuclei active on 24 hour cycle
- afferents from retina and other external inputs
- light cycle maintains 24 hour period
- continous light increases or decreases period depending on species
- synchronizes many other functions
- important role in reproduction via outputs to Pineal Gland which produces melatonin

Note Pineal Gland and Retina are major pacemakers in birds

Circadian Rhythms have significance effects on physiology and pharmacology
-
CORPUS CALLOSUM: Connects left and right halves of Cerebrum
CEREBRUM ANATOMICAL REFERENCES: Relative to Skull Bones

Frontal Cortex

Parietal Cortex

Occipital Cortex

Temporal Cortex

(Olfactory)
CEREBRUM FUNCTIONAL REFERENCES Five: Visual Area

Motor Area

Auditory Area

Somatosensory Area

Prefrontal Area
CREBRUM TOPOGRAPHICAL REPRESENTATION: Structures of cortex relate to distinct areas of body

Right body is represented in Left cortex and visa versa

Somatosensory Cortex
- somatotopic map has disproportionate representation of body areas
- areas with large amounts of receptors ie whiskers have larger representation in somatosensory cortex

Motor Cortex
- representation of muscles is proportionate to enervation ratio
- fine control muscles (extrinsic eye 1:10 motor unit:myocyte) have more representation than coarse control muscles (back 1:1000)

Visual Cortex (Occipital)
- map of visual field
- left eye is represented in right cortex and visa versa
- retnotopic map ie adjacent areas of retina are represented in adjacent areas of cortex

Autitory Cortex (Temporal)
- several maps
- left AND right auditory fields are represented on each side to allow sound location via timing differences of sound arrival between ears
NOTE major map is in Caudal Colliculus
PRORIOCEPTION SIGNS OF LOSS: Loss of Unconscious Proprioception
- cereballar malfunction
- uncoordinated movements
- dysmetria

Conscious Proprioception
- commonly reffered to as Proprioceptive Deficits
- loss of position sense
- involvement of cerebral cortex
- KNUCKLING RESPONSE via correction of weight bearing on dorsum of paw
- HOPPING REFLEX via maintaining leg under body when dangled so that weight is borne on one paw and animal is subjected to rapid lateral movements
- BLIND FOLDED WALKING

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