LECTURE 16: AUTONOMIC AND NEUROENDOCRINE SYSTEMS

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LECTURE 16 AUTONOMIC AND NEUROENDOCRINE SYSTEMS
REQUIRED READING Kandel text, Chapter 49

• Autonomic nervous system mediates visceral reflex
  responses that are involuntary and largely
  unconscious
• Autonomic nervous system consists of
• Motor neurons which act on smooth muscle, cardiac
  muscle, and exocrine glands
• Preganglionic CNS neurons whose axons synapse
  on these motor neurons
• Visceral sensory neurons
• Branches and subsets of external-sensing neurons
  (including somatosensory , olfactory, and
  retinal)
• Autonomic postganglionic neurons release
  neurotransmitters which act through metabotropic
  receptors on target cells
• Autonomic responses are coordinated with one
  another and with behavioral responses and
  emotions through the hypothalamus in the CNS

nicotinic receptors
always cholinergic
cholinergic or adrenergic
muscarinic or adrenergic receptors
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EXAMPLES OF AUTONOMIC FUNCTION
Regulation of heartbeat rate Regulation of
vascular constriction/dilation Pupil and lens
ocular reflexes Exocrine gland
secretion Glucose mobilization Sweating and
hair follicle erection Bladder filling and
emptying Sexual responses Alimentary and
bronchial reflexes Gut peristalsis
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THREE DIVISIONS OF THE AUTONOMIC NERVOUS SYSTEM
Sympathetic nervous system
Sympathetic system controls visceral responses
that prepare the body for rapid, intense
activity, often refered to as FIGHT-OR-FLIGHT
REACTION. Responses include accelerated
heartbeat, central artery constriction,
peripheral vascular dilation, liver glycogen
metabolism, rapid breathing. Other sympathetic
responses also work in balance with countering
parasympathetic responses to maintain body
homeostasis (counteraction to body stress).
Parasympathetic nervous system
Parasympathetic responses sometimes refered to as
the REST-AND-DIGEST STATE. Almost all visceral
targets receive both sympathetic
parasympathetic neuronal inputs.
Enteric nervous system
Enteric neurons form plexuses that surround and
extend along the length of the gut, including
stomach, small and large intestines. Enteric
system activate coordinated contraction of smooth
muscles to cause peristaltic constriction of
the gut. Most of enteric nervous system
functions independently of higher CNS control.
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ANATOMY OF SYMPATHETIC PARASYMPATHETIC NERVOUS
SYSTEM
Most SYMPATHETIC postganglionic neurons
are adrenergic (release E or NE) Most
PARASYMPATHETIC postganglionic neurons
are cholingeric
Site of spinal cord lesion injury can be rapidly
assessed by surveying damaged and surviving
autonomic reflex responses
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ANATOMY OF SYMPATHETIC PARASYMPATHETIC NERVOUS
SYSTEM
Generalized FIGHT response mediated by
sympathetic activation of the adrenal
gland, triggering epinephrine secretion into
circulation
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ANATOMY OF ENTERIC NERVOUS SYSTEM
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SENSORIMOTOR CONNECTIONS IN ENTERIC NERVOUS
SYSTEM ARE PREDOMINANTLY LOCAL
A local circuitry drives peristalsis in the
intestines
Pressure-sensing neuron senses gut
distension Acts through interneurons to activate
enteric motor neurons with axons projecting
rostrally causing squeezing of circular muscle
behind the distension Simultaneous inhibition of
other motor neurons with axons projecting
caudally relaxes downstream circular muscle
PERISTALSIS
FOOD DISTENSION
PRESSURE SENSING NEURON
CIRCULAR MUSCLE MOTOR NEURONS
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POST-GANGLIONIC NEUROTRANSMISSION LACKS
TYPICAL PRE- AND POST-SYNAPTIC SPECIALIZATIONS
Post-ganglionic neurons axon terminal lacks
clear-vesicle docking machinery. Multiple axonal
swellings (varicosities) are sites of
neurotransmitter vesicle accumulation. Post-synap
tic target (smooth muscle, gland, etc.) lacks
post-synaptic density. Target cell
neurotransmitter receptors are broadly
distributed on surface. Released
neurotransmitter acts diffusely over distances up
to 1 mm. Highly branched axons with multiple
varicosities enable post-ganglionic neuron to act
upon many cells in the target structure.
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DIFFUSE TRANSMISSION FROM GANGLIONIC AXONS
FACILITATED DISCOVERY OF THE FIRST CHEMICAL
NEUROTRANSMITTER
Parasympathetic vagus nerve activity slows
heartbeat rate, while sympathetic accelerator
nerve activity speeds heartbeat rate
TWO BEATING FROG HEARTS DISSECTED AND MAINTAINED
IN SMALL VOLUME SOLUTION HEART 1 DISSECTED WITH
INNERVATING NERVES ATTACHED HEART 2 DISSECTED
WITHOUT NERVES
Stimulation of vagal nerve slowed beating of
heart 1 After stimulation, transfer of heart
1s bathing solution to heart 2 slowed its
beating Stimulation of accelerator nerve speeds
beating of heart 1 After stimulation, transfer
of heart 1s solution to heart 2 sped its
beating THEREFORE, NERVE-INDUCED CARDIAC
RESPONSES ARE THROUGH SECRETED CHEMICAL
NEUROTRANSMITTERS (Vagal transmitter later
shown to be ACh, accelerator transmitter is NE)
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MECHANISMS OF AUTONOMIC MODULATION OF CARDIAC
FUNCTION
Parasympathetic release of acetylcholine reduces
cardiac output in two ways

• Muscarinic generation of Gbg directly activates a
  potassium channel (GIRK) in pacemaker
• cardiocytes, which slows their
  depolarization and rate of heartbeat.
• Muscarinic generation of Gai in heart muscle
  lowers cAMP and PKA levels, causing
• reduced opening of L-type calcium
  channels, thereby reducing force of heart
  contraction.

Sympathetic release of norepinephrine increases
cardiac output in two ways

• b1-adrenergic generation of Gas in pacemaker
  cardiocytes elevates cAMP and PKA levels,
• which reduces the threshold voltage for
  action potential initiation, thereby increasing
• rate of heartbeat.
• b1-adrenergic elevation of cAMP and PKA in heart
  muscle increases opening of L-type
• calcium channels, thereby increasing
  force of heart contraction.

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SENSORY INPUTS TO AUTONOMIC FUNCTION

• Our bodies sense deleterious changes and
  undertake automatic responses
• to maintain homeostasis.
• Sensory inputs eliciting autonomic responses
  include
• External sensations which trigger corrective
  reflexes
• Examples a) Ocular reflexes -- pupil dilation
  or constriction in response to light,
• lens stretching to adjust focus
• http//library.med.utah.edu/kw/hyperbrain/anim/ref
  lex.html
• b) Painful laceration -- vasoconstriction to
  limit blood loss
• sympathetic activation of coordinated
  fight/flight responses
• Visceral sensations induce homeostatic responses
• Examples
• a) Opposing sympathetic/parasympathetic control
  of heartbeat and blood pressure --
• If sympathetic activity drives heartbeat and
  artery constriction too much,

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PREGANGLIONIC FIBERS RELEASE SMALL MOLECULE AND
PEPTIDE NEUROTRANSMITTERS TO ELICIT COMPLEX
GANGLIONIC NEURON RESPONSES
Single or low-frequency preganglionic firing
releases Ach which activates nicotinic receptors
triggering fast EPSP in postganglionic
neuron. High-frequency stimulation releases more
Ach and LHRH peptide. The complex postganglionic
response consists of fast EPSP, slow IPSP
mediated by muscarinic receptor activation of
GIRKs, and delayed EPSP resulting from LHRH
binding to peptidergic receptors.
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SENSORY PATHWAYS OF SYMPATHETIC AND
PARASYMPATHETIC SYSTEMS PASS LOOP THROUGH BRAIN
STEM, BUT ALSO PROJECT TO CONSCIOUS CORTICAL AREAS
ASCENDING VISCERAL SENSORY PATHWAYS
DESCENDING AUTONOMIC RESPONSE PATHWAYS
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HYPOTHALAMUS COORDINATES PHYSIOLOGY AND
BEHAVIOR IN RESPONSE TO VISCERAL SENSORY INPUTS
EXAMPLE BLOOD OSMOLARITY HOMEOSTASIS
VISCERAL SENSORY INPUTS
Blood pressure Blood osmolarity
HYPOTHALAMUS COORDINATED OUTPUTS
Autonomic -- action on smooth muscles in
central and peripheral vasculature Behavioral
-- conscious thirst which drives search for
fluid intake Endocrine -- secretion of
vasopressin into blood, which promotes water
resorption by kidneys
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HYPOTHALAMUS CONTROLS HORMONE RELEASE FROM
PITUITARY GLAND BOTH DIRECTLY AND INDIRECTLY