PP EXAM 2

Nervous System Function

master controller of communication

send fast, efficient, and specific electrical and chemical signals

external/internal sensory input

integration (interpretation of sensory input)

motor output (response to stimuli by activating effector organs)

Central Nervous System (CNS)

integration/command center

brain + spinal cord

Peripheral Nervous System (PNS)

outside of the CNS

messages to and from brain and spinal cord

spinal and cranial nerves

Neurotransmitters

chemical

type is determined by receptor

Excitatory Neurotransmitters

cause depolarizations

ex) glutamate

Inhibitory Neurotransmitters

cause hyperpolarizations

ex) GABA

Dopamine

have both excitatory and inhibitory effects

General NT Release

1) action potential reached axon terminal

2) voltage-gated Ca+ channels open

3) Ca+ binds to sensor protein in cytoplasm (synaptotagmin)

4) Ca+ protein complex stimulates fusion and exocytosis of neurotransmitter in vesicle (which were previously bound by SNARE proteins

Synaptotagmin

Ca+ sensor in cytoplasm of cell

displaces part of SNARE so vesicle can fuse

Opening Na+/ Ca+ Channels

depolarization

EPSP (excitatory)

closer to firing

Opening K+/Cl- Channels

hyperpolarization

IPSP (inhibitory)

move membrane potential farther from threshold

Determining whether AP occurs or not

summation of EPSP/IPSP at inital segment of axon (next to axon hillock)

Spacial Summation

convergence of signals onto a single postsynaptic neuron; nearly simultaneous graded potentials combine

Temporal Summation

successive waves of NT release that add together

Generation of Acetylcholine

pyruvate dehydrogenase (glycolysis → krebs)

acetate thiokinase/ acetyl CoA synthetase

choline production = rate-limiting step; provided from diet

Acetylcholine Receptors

nicotinic and muscarinic

Nicotinic ACh Receptors

muscle + neuronal

stimulated by nicotine; ligand gated ion channels

found on motor end plate of skeletal muscle cells, autonomic ganglia, and parts of CNS

Muscarinic ACh Receptors (M1-5)

M1,3,5: excitatory

M2,4: inhibitory

stimulated by muscarine (from poisonous mushrooms)

found in CNS and plasma membrane of smooth + cardiac muscles and glands from autonomic motor neurons

GPCRs

Biogenic Amines

catecholamines (dopamine, norepinephrine, epinephrine)

indolamines (serotonin, histamine)

Catecholamine Biosynthesis

tyrosine → tyrosine hydrolase → dopa → dopa decarboxylase → dopamine → dopamine B-hydroxylase → norepinephrine → phenylethanolamine → epinephrine

Norepinephrine

used in both PNS + CNS

symphathetic neurons on PNS: smooth muscles, cardiac muscles, and glands

binds to GPCRs

used in CNS for wakefulness

Serotonin

used by neurons in middle region of brainstem

implicated by mood, behavior, appetite, and cerebral circulation

LSD + other hallucinogenic drugs agonist at 5-HT receptors

SSRIs used for depression

Amino Acids

GABA

Glycine

Aspartate

Glutamate

GABA

most common NT in brain (used by 1/3 of brains neurons)

inhibitory (opens Cl- channels)

involved in motor control; degeneration of GABA-secreting neurons in cerebellum result in Huntingtons Disease

Glycine

inhibitory (opens Cl- channels); hyperpolarization

allows for antagonistic muscle groups to relax (ex bicep/tricep movement)

important for relaxation of diaphragm + digestion

blocked by strychnone (causes death via asphyxiation)

Glutamate

major excitatory NT in brain (EPSPs)

all receptors are ligand-gated ion channels (NMDA, AMPA, Kainate)

Endogenous Opioids

polypeptides

produced by brain + pituitary gland

produce euphoria post workout

Endocannabinoids

bind to same receptors that bind THC

released directly from plasma membrane without vesicle

retrograde NTs inhibit more NT release

allow EPSPs to have greater effect by inhibiting IPSP neurotransmitters

may enhance learning + memory and have been shown to induce appetite

THC impairs learning + memory bc it is widespread and not controlled

Nitric Oxide

produced in CNS + PNS from L-arginine (amino acid)

no vesicle needed

activates cGMP as second messenger

causes blood vessel dilation

may act as retrograde NT

Carbon Monoxide

derived from heme breakdown

activates production of cGMP in target cells

used in olfactory epithelium and cerebellum

ATP and Adenosine

cotransport released via vesicles with another neurotransmitter

classified as purines → bind to purinergic receptors

P1 for ATP (purinergic receptors)

P2 for Adenosine

co-released with norepinephrine → stimulate blood vessel constriction

co-released with Ach → intestinal contraction

Autonomic Nervous System

motor neurons

innervate smooth muscle, cardiac muscle, glands, and adipose tissue

make fast adjustments to ensure optimal support for body activities

subconscious control

Efferent Pathways

heavily mylinated axons (CNS -→ SNS)

axons are 2 neuron chain (pregang and postgang

Preganglionic Neuron

lightly myelinated axon

Ach

Postganglionic Neuron

no myelin

extends to effector organ

NE/ACh

Somatic Nervous System

effector = cardiac muscle

voluntary + stimulatory

N = Ach

fast conduction due to thick myelinated fibers

denervation → paralysis/spasm

Autonomic Nervous System

effectors = cardiac + smooth muscle, glands

involuntary

efferent pathways = 2 neurons

slower conduction because only preganglionic neurons are myelinated

NTS = Ach (pregang), NE/ACh (postgang)

target organ response = stumulatory/inhibitory

denervation: denervation hypersensitivity

balance of parasympathetic vs sympathetic activities

Heart Transplant

denervated heart; cannot be activated by ANS

elevated resting heart rate

blunted exercise rate response

loss of heart rate variability

alter drugs that work on ANS

Sympathetic Division of ANS

mobilizes body during extreme situations

fight-or-flight responses

E activities: exercise, excitement, emergency, embarrassment

main NT: NE (acts via adrenergic receptors)

preganglionic fibers leave CNS via thoracic and lumbar nerves

ganglions located along spinal column

Parasympathetic Division of ANS

performs maintenance activities and conserves body energy; slows heart, dictates normal activity levels of the digestive + urinary systems

main NT: ACh

housekeeping; parachute brings back down

D activities: digestion, defecation, diureses

most preganglionic fibers located within target organs

Neurotransmitter for Sweat Glands

ACh

(even though sympathetic)

Divergence

one pregang neuron synapses on several postganglionic neurons at different levels

Convergence

several preganglionic neurons at different levels synapse on one postganglionic neurons

Collateral Ganglia (SNS)

neurons that exit spinal cord below diaphragm (T5-L3) → splanchnic nerves

ex) celiac ganglion, superior mesenteric ganglion, inferior mesenteric ganglion

postganglions that innervate the digestive, urinary, and reproductive systems

Adrenal Medulla

fibers of thoracic splanchnic nerve pass directly to adrenal medulla (no ganglions)

sympathetic stimulation of EPI and NE into blood (as hormones)

Parasympathetic Cranial Nerves

Oculomotor Nerve (III), Facial Nerve (VII), Glossopharyngeal Nerve (IX), Vagus Nerve (X)

Oculomotor Nerve

(III)

narrows pupil and focuses lense

Facial Nerve

(VII)

tear, nasal, and salivary glands

Glossopharyngeal Nerve

(IX)

protoid salivary gland

Vagus Nerve

(X)

cardiac, pulmonary, and esophageal plexus

thoracic and abdominal viscera

Cholinergic Neurotransmitter

ACh

only NT released by PNS

released from all preganglionic neurons (sym/parasym)

axon terminals/boutons of the presynaptic neuron contain vescicles filled with Ach and other cotransmitters (ATP)

Choline Acetyl Transferase

rapidly synthesizes ACh
located in cytoplasm

Acetylcholinesterase

breaks down ACh and makes it into choline and acetate

Cholinergic Receptors

two types:

• nicotinic (Nm/Nm)

• muscarinic (M1-5)

Nicotinic Receptor (ACh)

found on neuromuscular junction (SNS), all postganglionic cell bodies of both sym/parasym divisions, cells of adrenal medulla, ligand0gated ion channels

fast, short-acting

always stimulatory; causes depolarization; producing APs

Muscarinic Receptors (ACh)

occur on all effector cells of PNS and sweat glands

g-protein coupled receptors

effects are slow + long lasting

can either be inhibititory/excitatory

depends on receptor subtype

Muscarinic M3/M5 Receptor

smooth muscle, glands

depolarization → stimulatory

secretion of glands, contraction of smooth muscle

GPCR actived by Ach

Muscarinic M2 Receptor

heart

inhibitory/ relaxes

hyperpolarization

Adrenergic Neurotransmitter

usually norephrine (NE)

dopamine in kidney

only sympathetic NS uses

Adrenergic Receptors

alpha (α1 and α2), beta (β1. β2, β3)

all act using G-proteins and second messenger systems

α → more sensitive to NE

β → more sensitive to blood EPI

α1 Adrenergic Receptor

Gq protein (IP₃ increases intracellular Ca²⁺)

constricts smooth muscle cells

vasoconstriction

pupil dilation

GI tract sphincter constriction (slower emptying)

α2 Adrenergic Receptor

Gi inhibitory protein

located on presynaptic axons

stimulation → inhibition of NE

inhibits pancreas insulin secretion

inhibits secretion in GI tract

slows BP

β1 Adrenergic Receptor

Gs (stimulatory)

heart contractions

kidney renin release

stimulated by NE

β2 Adrenergic Receptor

Gs or Gi

heart (lesses extent)

blood vessel to skeletal muscle vasodilation

smooth muscle of lungs bronchodilation

uterine and GI tract smooth muscle relaxation

β3 Adrenergic Receptor

Gs

bladder

adipose tissue → triglyceride breakdown

urinary bladder → relaxation + prevention of urination

Adrenergic Neurotransmission Termination

1. diffusion away from synapse (later metabolism in liver + plasma)

2. reuptake into neurons (metabolized or recycled by presynaptic transporters

3. uptake into glia/ smooth muscle (metabolized)

Metabolism Enzymes

for third step of adrenergic neurotransmission termination

Catecholamines are metabolized by 2 enzymes

COMT (catechol-o-methyl transferase)

MAO (monoamine oxidase)

Why Sympathetic Effects Last Longer than Parasympathetic Effects

main neurotransmitter: Norepinephrine

→ inactivated more slowly than ACh

→ indirectly acting NT; uses second messenger system

→ EPI is released into blood and remain there until destroyed by liver

Unique Roles of Sympathetic Nervous System*

adrenal medulla

sweat glands

arrector pili muscles

kidneys

most blood vessels

Unique Roles of Sympathetic Division

thermoregulation

release of renin from kidneys

metabolic effects

Thermoregulatory Responses to Heat

heat to skin → reflec dilation of blood vessels

fever → widespread dilation of blood vessels bringing warm blood to surface and activating sweat glands to cool the body

low temperature → blood vessels constriction and blood is retained in deeper vital organs

Sympathetic Metabolic Effects That are not Reversed by the Parasympathetic Division

increase if metabolic rate of body cells

increase blood glucose levels

mobilizes fat as a food source

stimulates the reticular activating system (RAS) of the brain; increased mental alertness

Sympathetic Tone/Vasomotor Tone

SD: controls blood pressure and keeps the blood vessels in a continual state of partial constriction

ST: constricts blood vessels and causes blood pressure to increase as needed

prompts vessels to dialate if blood pressure is to be decreased