Lecture 2.13 - SysNeurobio III; Circadian, Myofibers, Innervation

• Circadian cycle - throughout the day, controlled physiologically

  • Controls:

    • Alertness, muscle contraction speed, body temperature, melatonin level, cortisol, blood pressure

  • Doesn’t control homeostasis from moment to moment

Circadian rhythm SCN

• CR relies on a molecular Negative feedback loop

  • BMAL1 and CLOCK are transcribed

  • They begin DNA transcription, producing PERs and CRYs

  • PERs and CRYs inhibits production of transcription factor, working on 24 hour cycle (strong correlation)

• In hypothalamus:

  • In Suprachiasmatic nucleus (SCN)

    • Found there were strong correlations of BMAL1 and Clock transcription or PERs and CRYs production occured within a 24 hour cycle

Specific steps - Circadian Rhythm molecular Neg feedback loop

LOCATION: Occurs inside the neurons of the Suprachiasmatic nucleus (SCN) inside the hypothalamus

STEPS:

1. CLOCK and BMAL1, transcription proteins, form a transcription factor complex

2. They trigger DNA transcription for the proteins PERs and CRYs, which accumulate slowly in the cytoplasm

3. After enough PER and CRY proteins accumulate, they Inhibit CLOCK and BMAL1, which then stops the production of more PERs and CRYs

• Negative Feedback

  • PER and CRY will degrade, and when the levels are lower, CLOCK and BMAL1 will trigger transcription again, and the cycle restarts

  • This occurs over a 24 hour period

Function of Circadian rhythm proteins

• The proteins changes neuron firing rate - Interpret Daytime vs Nighttime

  • When CLOCK/BMAL1 is active (low PER/CRY):

    • SCN neurons fire rapidly

    • → Brain interprets this as daytime

  • When PER/CRY accumulates and shuts BLOCK/BMAL1 off:

    • SCN neurons fire slowly

    • → Brain interprets this as night

• When SCN knows the “time” - sends signals to the rest of the body; regulates

  • melatonin release (pineal gland)

  • cortisol timing

  • body temperature

  • metabolism

  • alertness

  • sleep–wake behavior

• Light → retina → SCN molecular clock → neuron firing rhythm → hormone timing → sleep/wake behavior

Suprachiasmatic nucleus (SCN)

• Located in the hypothalamus

• Determines what “time of day” it is for your body and coordinates daily physiological rhythms

  • Via CLOCK + BMAL1 and PER/CRY 24-hour cycle

    • During DAY - SCN neurons fire FAST (low PERs/CRYs)

    • During NIGHT - SCN Neurons (high PERs/CRYs)

• The firing rhythms of neurons → control hormones (melatonin, cortisol, body temp, sleepiness)

• The reason neurons fire rhythmically is because the genes inside them oscillate

SCN hormone release

• SCN controls many things over 24 hour cycle, including hormone release

  • Tropic hormones - target different endocrine glands, 24 hour period (cyclical)

    • Melatonin

      • Produced in pineal gland - possibly controlled by light

    • Cortisol

    • Androgyn

    • Estrogen

    • IGF

• Not entirely genetic

  • Environment impacts circadian cycles

Sympathetic Nervous system

• Most active during stress, excitement, or physical activity

• “Fight or flight”

  • Increases HR, breathing rate, directs blood to working muscles, not gut

• Innervation - Thoracic area

  • Heart - increases heart rate and how hard it’s beating

  • Small intestine - turns off absorption and digestion

Parasympathetic Nervous System

• Most active during rest

• “resting and digesting”

• Redirects energy toward maintenance activities like digestion

• Innervation - Coccyx and brain stem

  • Heart - slows down heart rate, softer beating - less blood flow

  • Small intestine - turns on digestion and absorption

Sympathetic vs Parasympathetic

SNS and PNS - Innervation and Chart

• SNS - Thoracic

• PNS - Brain stem

• Organs tend to have Innervation from both systems - Dual-innervation

  • Heart:

    • SNS: increases heart rate, how hard the heart is beating

    • PNS: slows down heart rate, makes it beat less hard - less blood flowing

  • Small intestine:

    • SNS: Turns off digestion and absorption

    • PNS: Turns on digestion and absorption

  • Eye:

    • SNS: pupil dilates, see more light

    • PNS: pupil shrinks, at rest

  • Sweat glands:

    • SNS: localized sweating

    • PNS: general sweating

• Opposite effects from SNS and PNS = Antagonistic

Not dually innervated effects

EAAKL - Emergency Actions Are Key — Lacrimate later.

SNS controlled

• Erector pilli muscles of skin

  • PNS: nothing

    • Muscle - will just relax under parasympathetic conditions

  • SNS: contract, causing hair to stand up, goosebumps

• Arterioles

  • PNS: nothing

  • SNS: vasoconstriction

• Adrenal medulla

  • PNS: nothing

  • SNS: secretes epinephrine

• Kidney

  • PNS: nothing

  • SNS: increases renin secretion, which increases BP

PNS controlled

• Lacrimal glands of eyes (relax)

  • PNS: stimulates tear secretion

  • SNS: nothing

Neurons of PNS vs SNS

• Preganglionic neuron

  • PNS: Long

  • CNS: Short

• NT:

  • Same for both: Acetocholine

• Receptor:

  • Same for both: Nicotinic cholinergic receptor

• Postganglionic neuron

  • PNS: Short

  • CNS: Long

• NT :

  • PNS: ACh - Muscarinic cholinergic receptor

  • CNS: NE - Adrenergic receptor

PNS Neurons

• Preganglionic neuron - Long

• NT - Ach

• Receptor - Nicotinic receptor

• Postganglionic neuron - Short

• NT - ACh

• Receptor - Muscarinic cholinergic recptor

SNS Neurons

• Preganglionic neuron - Short

• NT - Ach

• Receptor - Nicotinic receptor

• Postganglionic neuron - Long

• NT - NE

• Receptor - Adrenergic receptor

NE and Adrenergic receptor

• The same NE ligand can cause different responses in different tissue based on the specific receptors

• Different receptor subtupes: a1, a2, B1, B2

• During SNS:

  • B1 → Heart Beats faster and stronger

  • a1 → Vasoconstriction (anterioles)

    • Reduces blood that goes to skin, gut (sick to stomach), kidney, salivary glands (dry mouth)

  • No need to know a2

  • B2 → Lungs, vasodilation - allowing to Breath more

Vasodilation/constriction - how does SNS input along control it?

• Arterial - smooth muscle tubes

  • Contract (vasoconstriction) or relax (vasodilation)

  • Higher pressure when you drink water, lower when you’re dehydrated - natural pressure in bloodstream, always pushing against muscles

• Arteriolar smooth muscle has adrenergic receptors

  • More SNS signaling = more contraction = Vasoconstriction

    • No Muscarinic (PNS) because they don’t do anything during PNS

  • Less SNS signaling = less contraction = Vasodilation

  • Always some pressure - Basal sympathetic signaling

Kidneys / Adrenal medulla is only innervated by…

• SNS

  • SNS - preganglionic sympathetic neuron that leads to the Adrenal Medulla, which produces adrenaline in response to stress

  • Remove adrenergic response = stop producing

    • Don’t need a 2nd neuron to stop

Neuromuscular junction (NMJ)

• Neuromuscular junction - Somatic motor neuron (from CNS) innervate skeletal muscle for voluntary movements, SYNAPSE

• Motor neuron axon terminal → NMJ → muscle fiber

NMJ NT movement

• Presynaptic membrane/neuron

  • Ca2+ triggers releases ACh from synaptic vesicles

  • ACh released into NMJ

• Postsynaptic membrane

  • ACh binds to nicotinic recepetors

• Causes skeletal muscle depolarization via entry of Na+ ions into the cell

• Contraction

Motor unit

• 1 motor neuron innervates and all the muscle cells it’s innervating (1 or more)

Muscle belly

Depending on size, can be innervated by multiple muscle

Myofiber

• Muscle cell

• Excitable

  • AP spreads along membrane (sarcolemma)

• Contractable

  • Get shorter when excited

• Extensible

  • Can stretch

  • Mot due to action potential

Myofiber anatomy

• Sarcolemma - outer membrane, where AP travels

• T-tubules - conduct AP, trigger Ca2+ release

  • Holes in sarcolemma - where AP passes to the inside of the cell

• Many mitochondria, underneath sarcolemma

• Multi-nucleated - on the outside of the cell, because the inside is where the proteins are, while the nuclei do the repairs on the outside

• ***Satellite cells = muscle stem cells sitting outside the fiber, repairs muscle cells

• Myofibril - a type of muscle protein, inside myofiber

  • Other proteins: Actin and Myosin

• Terminal cisternae - releases Ca2+ in response to AP traveling through T-tubule

• Sarcoplasmic reticulum - a smooth ER specific to Myofibers, only stores Ca2+