L11: ANS I

ANS- involuntary NS, visceral motor system (blood vessels, sweat glands)- control bodily function, reg organ/tissues- cellular targets

• smooth & cardiac muscle (excitation/inhibition)• epithelial ion transport (absorption/secretion)• hormone & mucous secretion (gut, pancreas, salivary gland)• metabolism (adipose, liver)• immune cells (↔ ANS NT)• some tissues have autonomic nerves with unknown function

- mouse vas deferans: noradrenergic (pro-contractile), cholinergic (unknown)- specific actions at tissue/organ

• simple reflex (hot→remove hand, blood flow) • coordinated regulation of multiple sites• complex behaviour (stress, anxiety, pain)• features: precise, integrative, flexible

- endocrine system• homeostasis: maintain internal set pt for survival• allostasis: maintain balanced system to adapt to envm/need [predictive/reactive] “achieve stability via change”

Functional Anatomy of ANS- 3 components

• sympathetic- in CNS & PNS, ✗ function without CNS

• parasympathetic- in CNS & PNS, ✗ function without CNS

• enteric- in GIT, ✓ function without CNS, ✓ influenced by CNS/symp/para- complete reflex circuit (sensory, interneuron, motor, IPANS/intrinsic primary afferent neurons)

• all 3 depend on CNS activation- symp & parasymp

• defined by anatomy = location of preganglionic neurons

Neurotransmitters- many subtypes of ACh & NA receptors- many transmitters in ANS (NO, ATP, peptide), esp at synapse- co-transmission: >1 transmitter can be released from a synapse- understand this complexity to design treatment with ↑efficacy & specificity

Sympathetic NS- thoraco-lumbar (thorasic part of spinal cord)- central neuron at brainstem/spinal cord- symp ganglia closer to CNS- short preganglionic neuron + long postganglionic neuron

Structure- preganglionic neuron in thoracolumbar cord (intermediolateral nucleus)- preganglionic axons project via spinal nerves → connect with ganglion cells- 2 types of symp ganglia

• paravertebral ganglia (sympathetic chain)• prevertebral ganglia (mesenteric ganglia)• adrenal medulla → activated → ✗ form postganglionic axons but secrete hormones (A & NA) into circ →

widespread effect ꔄ sympathoadrenal system

Neurotransmitters: conventional viewCNS ganglia organs

symp

para ACh

NA (most tissues)

TransmittersACh = acetylcholine NA = noradrenaline

(norepinephrine)

ACh

ACh

Receptorsnicotinic (N) or muscarinic (M) a or b adrenoceptors

ACh (few tissues)*(M)

(N)

(N)

(M)

PNSpreganglionicneuron

postganglionicneuron

autonomicganglia

sweatglands

centralneuron

Sympathetic nervous system: structurePreganglionic neurons in thoracolumbar cordAxons project via spinal nerves

intermediolateral nucleus

Purves et al 2012

There are two types of sympathetic ganglia:

Paravertebral ganglia (aka sympathetic chain)Prevertebral ganglia (aka mesenteric ganglia)

PLUS sympathetic preganglionic neurons innervate the adrenal medulla. If activated, these adrenal cells secrete the hormones, adrenaline and noradrenaline, into the circulation, having widespread effects.Therefore sometimes the term “sympathoadrenal system” is used.

prevertebral

paravertebral

Sympathetic nervous system: structurePreganglionic axon connections with ganglion cells

Gibbins IL (1997) in Encyclopedia of Human Biology, 2nd ed. ISBN 9780122269707

FunctionConventional View- fight-or-flight

• ↑HR, ↑contractile force of heart• ↑blood flow to skeletal muscle• ↓blood flow to gut, ↓gut motility [modulate enteric]• relax airway

- mass activation & coordination of many symp pathways at once to overcome/escape a threat• adrenal medullary nerves → catecholamine hormone spread through bloodstream• CNS activates many preganglionic pathways at once• some preganglionic neurons ✓ many axon collaterals → activate many postganglionic neurons at once (amplification)

Realistic View- fight/flight underestimate diversity & sophistication of symp- symp is essential for normal living (BP, small ∆ temp), mass activation in extreme situation- many functions ✗ link to fight/flight (reproduction, voiding behaviour)- adrenal medulla nerves ✗ always activated- ✓ precisely & independently activate indu cells/tissues/organs

Parasympathetic NS- cranio-sacral (brain stem - bottom sacral)- parasymp ganglia closer/within organ- long preganglionic neuron + short postganglionic neuron

Structure- preganglionic neurons in:

• brainstem nuclei → axons project via cranial nerve(1) Edinger-Westphal nucleus (midbrain)

oculomotor nerve (III) (eye) ciliary ganglion control sphincter pupillae, ciliary muscle

(2) salivatory nuclei (upper medulla)facial nerve (VII) & glossopharyngeal nerve (IX) submandibular, spheno-palatine, otic ganglia control lacrimal, salivary, sublingual, nasal & palatine glands

(3) dorsal motor nucleus of vagus & nucleus ambiguus (middle medulla) vagus nerve (X)unnamed microganglia (near/outer surface of thoracic & abdominal organ) many functions

• sacral spinal cord (intermediolateral nucleus) → axons project via spinal nerve- sacral postganglionic neurons in pelvic plexus (inferior hypogastric plexus)

• pelvic ganglia = mixed ganglia (1/3 is symp neurons)• unusual• ganglion neurons have unusually long axons → vulnerable to surgical injury

FunctionConventional View- rest-and-digest (opposite action to fight/flight)

• ↓HR, ↓contractile force of heart• ↑gut motility• constrict airway

- limited mass activation of diff type of parasymp pathways• nth like adrenal gland → ✗ release A into blood to affect all organs at once• preganglionic neurons has less axon collaterals to simultaneously activate postganglionic neurons • coordination of parasymp pathway btw regions is done by brain mechanism

Realistic View- underestimate diversity of parasymp- parasymp pathway activated in many other situations- assume extreme situation when nth much is happening- some functions ✗ link to rest/digest (bladder, sexual)

Mass activation and coordination is achieved by:• If the adrenal medullary nerves are activated,

catecholamine hormones spread through the bloodstream.

• The CNS activates many preganglionic pathways at once.

• Some preganglionic neurons have many axon collaterals so can activate many postganglionic neurons at once.

PRE

POST

POST

POST

POST

Sympathetic nervous system: functionConventional view: mechanism

intermediolateral nucleus

Parasympathetic nervous system: structurePreganglionic neurons in two sites: (2) sacral spinal cordAxons project via spinal nerves

Purves et al 2012

Are Symp & Parasymp Antagonistic- sometimes- fight/flight & rest/digest = inaccurate & oversimplify ANS function = incorrect assumption that symp & parasymp always act

antagonistically at cellular/tissue/organ- limiting concept for bladder & sexual function

Sympathetic Parasympathetic

genuine antagonism at cellular level ↑HR (SA node)relax airway

↓HRcontract airway

functional antagonism in tissue/organ but via diff cells(common, not necessarily opposite)

contract pupil dilator musclecontract base of bladder (continence)

contract pupil sphincter musclecontract body of bladder (voiding)

diff but ✗ opposite action(some tissues only have 1 type of innervation)

serous salivary secretionsweatlipolysis-

mucous salivary secretion--tear (lacrimal glands)

L16: UPPER MOTONEURON

- central sulcus: separate frontal (movement/planning) & parietal (perception) precentral gyrus = primary motor area

- epilepsy• brain surgery while patient is awake (brain ✗ pain R)• stimulate motor area → contralateral movement• further frontal 1° motor area → need more current, bilateral, multi-joint, complex movement

Cerebral Cortex- cerebral cortex (motor cortex) → brainstem → spinal tract → spinal cord- brainstem locomotor region, postural/anticipatory movement- corticobulbar tract (face)- the rest are corticospinal tract

• cortex → brainstem → 90% cross over at caudal medulla → pyramidal decussation → lateral corticospinal tract go to lateral white matter of spinal cord → directly on motoneuron (20%)

• 10% ✗ cross over, stay ipsilateral via ventral corticospinal tract- brainstem: lower motoneuron, corticobulbar

Topographic Map of Movement in 1° Motor Cortex- magnification = importance ✗ equal cortical space for body part

- digit/lip/face: ↑representation- plastic

Purposeful Movement- from prolonged microstimulation in 1° motor cortex- monkey

• no matter place hand at where → hand always go to mouth• stimulate another location of motor cortex → hands always go to chest• motor cortex encodes the things we always do

Motor Maps- functionally related movements (rather than topographic mapping)- represent movements we do all the time

Mirror Neurons- higher order motor- record lateral premotor cortex → find neurons that respond to reach/grab- the same neuron fire AP when monkey sees other people doing it (gotta be exact action)- learn via copying

Signs / Symptoms

- upper motoneuron• upper motoneuron usually inhibits spinal motoneuron → now ✗ brain input → unmask inhibited signal → more active• Babinski Sign

- clinical diagnostic of motor system damage (brain ✗ link to spinal cord)- run sth on foot- normal plantar response → toes down (flexion)

extensor plantar response → toes up, fanning - unmask inhibited signal → reemergent of infant reflex

Upper Motoneuron Lesion Lower Motoneuron Lesion

- weakness- spasticity (spasm)

• ↑ tone• hyperactive deep reflex• clonus

- Babinski’s sign- loss fine voluntary movement (still ✓ posture)

- weakness, paralysis, ✗ activity- ↓ superficial reflex- hypoactive deep reflex- ↓ tone- fasciculation (brief contraction) & fibrillation - severe muscle atrophy → degenerated

3. The primary motor cortex and the premotor area

The corticospinal and corticobulbar tracts

Cerebellum- supplementary motor- modulatory part of motor control (upper motoneuron)

• cerebellum: ↔ cerebral cortex & brainstem (diencephalon), ✗ project to spinal cord• basal ganglia: ↔ cerebral cortex

- large portion of cerebral cortex projects to cerebellum- function

• coordinate timing & seq of muscle action → smooth movement• maintain muscle tone• motor learning → less clumsy• plastic → modify muscle planning seq for complex movement

- cerebellar cortex, white matterdeep cerebellar nuclei → output → descending tract

- input• motor/sensory cortex (that will project to spinal cord)• spindle via dorsal nucleus of Clarke (proprioception)• vestibular input

- output• motor cortex• motor area in brainstem (colliculospinal, vestibulospinal, reticulospinal) → lower motoneuron in medial ventral horn

- error detector corrector• motor command → error signal• use circuit to modulate descending motor command

Ataxia- cerebellar dysfunction- after repetitive action still ✗ control movement (esp beginning & ending)- cerebellum → smooth movement, precise