neurophysiology

lecture

Brain

• Ventral roots - carry info from brain to body

• Dorsal roots - carry info from body to brain

• Basal ganglia - decides which motor movements are on/off

• Blood-brain barrier - structures that surround CNS capillaries

  • Prevents chemical/microbial damage

    • Prevents diffusion of harmful substances

Imaging

• PET - radioactive water/glucose is injected to patient

  • Good spatial resolution (sharp image)

  • Poor temporal (cannot see live changes)

• fMRI - measure how long it takes for H+ to go back to normal

  • Oxygenated protons are slower that deoxygenated

  • Good spatial; poor temporal (better than PET)

• MEG - magnetic field that can be detected externally

  • Better spatial resolution than EEG

  • Good temporal

• EEG - electrical field; can be detected from the scalp

  • Similar temportal to MEG

Properties

• Voltage (V) - aka membrane potential

  • Difference in electrical potential between inside and out the cell

• Current (I) - aka membrane current

  • Number of electrical charges flowing

    • ions leaving the cell; - ions coming in

      • Hyperpolarization - more negative

    • ions leaving the cell; + ions coming in

      • Depolarization - close to 0

• Resistance (R) - size of ion channels

  • Smaller/narrow channels = more resistance

• Capacitance (C) - how quick a neuron can respond to a current entering the cell

  • More membrane surface area = more c

  • Thicker membrane = lower c

    • Mylein lowers Cm without increasing axon diameter by insulating parts of the axon

• Ra - axial resistance: how easily an action potential moves down the axon

  • Larger axon = lower Ra

Membrane Potential/Diffusion

• Resting membrane potential = -60mV

  • Ion pump channels (active transport) maintains

• K+ = higher concentration inside cell

• Na+ = higher concentration outside cell

• Ca+2 = higher concentration outside cell

• Cl- = higher concentration outside cell

Na/K Action Potential

• Rest - Na/K channels are closed

• Strong depolarization - Na opens first; K is delayed

• Repolarization - Na channels are closed and inactivated; K channels are opened (+ charges flowing out of the cell) ⇒ absolute refractory period (neuron cannot fire again)

• Hyperpolarization - Na channels are closed; K channels start to close ⇒ relative refractory perioid (neuron can fire again w a stronger stimulus)

Ca release and neurotransmitters

• Action potential depolarizes axon terminal

• Depolarization opens Ca channel and it enters the cell

• Ca entry triggers exocytosis ⇒ neurotransmitters in synaptic vesicles are released

  • Leftover Ca from first action potential ⇒ more vesciles released ⇒ bigger response = short-term facillitation

• Neurotransmitter binds ⇒ postsynaptic response

Major Neurotransmitters

• Brain

  • Glutamate - excitatory

  • GABA - inhibitory

    • GABA_A - Cl

    • GABA_B - K

• Acetycholine (ACh) - excitatory neurotransmitter in neuromuscular junction

Summation

• Temporal summation - neurons have repeated inputs at the same synapse

  • Higher time constant - 1 response to all inputs

    • V changes slowly

  • Low time constant - separate responses for each input

• Spatial summation - neurons have inputs at different synapses at the same time

  • Higher length constant - signals from inputs easily spread from the different regions

Memory

• AMPA/NMDA channels - iGluRs (excitatory ionotropic channels)

  • AMPA - opens with glutamate binding

  • NMDA - Mg blockage when cell is hyperpolarized; opens with presyn glutamate and postsyn depolarization; permeable to Na⁺, K⁺, and Ca²⁺

    • Neurons that fire together

• Long-term potentiation (LTP) - postsyn responses lasting longer

  • Requires NMDA activation

    • Ca enters cell when NMDA opens ⇒ effective AMPA or more AMPA ⇒ increases postsyn responses over time

  • Synapse-specificity - only stimulated synapses get LTP

  • Associativity - strong stimulation in 1 synapse and weak in the other synapse = LTP in both

  • Pavlov conditioning - condition stimulus and unconditioned stimulus are wired together

Sensory Transduction

• Receptive fields - reigon where if a stimulus is detected a neuron will respond

  • It becomes larger as it moves to the brain due to overlapping inputs from multiple neurons

• Lateral inhibition - creates larger contrast between a stimulus from one neuron by inhibiting the surrounding neurons

• Mechanotransduction - mechanical energy is used to change membrane potential

  • Somatosensory mechanoreceptors - neurons with specialized axon terminals that have mechanically gated ion channels

    • Opens with membrane tension or structural proteins

• Slowly adapting receptor - fires throughout stimulus

  • Steady skin indentation

  • Merkel’s disks - indentation

  • Ruffini’s endings - stretch

• Rapidly adapting receptor - only fires with stimulus starts/ends

  • Skin indentation changes

  • Pacinian corpuscles - high freq skin vibrations

  • Meissner’s corpuscles - skin motion

Hearing

1. Air pressure changes (sound)

2. Fluid movement (inner ear)

   • Fluid-filled cochlea - 3 chambers with ionic solutions

     • Scala vestibuli - high Na, low K

     • Scala media - low Na, high K (+80mv)

     • Scala tympani - high Na, low K

   • Helicotrema - allows fluid to move back anf forth on basilar membrane

3. Detected by hair cells (changes membrane potential)

   • In basilar membrane - tonotopic (receptive fields mapped by sound frequency)

   • Outer hair cells - amplifies basilar membrane

   • Inner hair cells - sound energy ⇒ signal

     • Has stereocillia that bends from the current from the mechanical ion channels

   • Mechanotransduction - K+ enters the cell and depolarizes it

     • Stereocillia bends and the ion channels open

4. Goes to the spiral ganglion (ear) ⇒ auditory nerve ⇒ brain stem

5. Becomes bianural at the superior olive

   • Can differentiate sound between the 2 ears

6. Auditory cortex

Smell/Olfaction

• Olfaction - different receptors for different smells but same pathway

  1. Odorant molecules enter nose through breathed air

  2. Binds to g-protein (metabotropic) receptors on olfactory epithelium

  3. cAMP increases and the cell depolarizes due to Cl leaving the cell and Na/Ca entering

  4. Signal projected to olfactory bulb

  5. Sent to olfactory cortex

Taste/Gustation

1. Taste ligands bind to receptors

   1. Different tastes have different receptors

      1. Metabotropic - bitter, sweet, savory(umami)

      2. Ionotropic - sour, salty

2. Creates Ca that signals release of neurotransmitters onto primary sensory neurons

Vision

1. Cornea ⇒ Pupil ⇒ Lens ⇒ Photoreceptors

   1. Rod photoreceptor - longer outersegment; for nighttime

      1. Mostly in peripheral retina

   2. Cone photoreceptor - shorter outersegment; colors

      1. Mostly in fovea (center of retina)

2. Light hyperpolarizes the photoreceptor cell (less glutamate released)

   1. Rhodospin is activated

   2. cGMP levels decrease (becomes GMP)

   3. Closes Na channels

3. ON/OFF bipolar cells

   1. OFF - AMPA receptors: depolarized in the dark

      1. Photoreceptors release glutamate that depolarizes OFF bipolar cells

   2. ON - mGluR6 receptors: depolarized in the light

      1. Photoreceptors release glutamate that hyperpolarizes ON bipolar cells

4. Ganglion cell axons projects to forebrain

Parasympathetic/Sympathetic

• Pregang neurons relases acetylcholine and uses a nicotinic receptor

• Sympathetic - postgang neurons release norepinephrine and organs have alpha/beta adrenergic (metabotropic) receptors that can be excitatory/inhibitory

• Parasympathetic - postgang neurons release acetylcholine and organs have muscarinic receptors that are excitatory or inhibitory

• Sympathomimetic meds - mimics sympathetic nervous system

  • Beta adrenergic enhancing drugs

• Parasympathomimetic meds - mimics parasympathetic nervous system

  • Betablockers

  • Stimulation of vagus nerve

Muscle Contraction

• Somatic motor neuron releases acetylcholine at the neuromuscular junction and it binds at the motor end plate

• Na enters the cell ⇒ action potential

• Action potential travels down t-tubules

• Opens 2 channels one of which is at the sacroplasmic recticulum (ryr) and causes the release of Ca

  • Other is in t-tubule (DHP)

• Ca binds to troponin on the actin filament which causes a binding site to be exposed

• Myosin binds to it

  • Power stroke - inorganic phosphate is released from the myosin head, allowing for it to rotate and bind to actin

• ATP is needed to release the actin and myosin (end of contraction)

• Fast motor units - white; easily fatigued; high innervation #; large alpha neurons

• Slow motor units - red; fatigue-resistant; low innervation #; small alpha neurons

Muscle Spindle

• Reports muscle length via 1a axons to alpha neuron ⇒ contraction

• Gamma motor neurons (intrafusal) exist in the muscle spindle to allow contraction while alpha is contracting

  • Without it muscle spindle would stop signalling

• Myostatic reflex - contracts a muscle in response to increased muscle length

Golgi Tendon Organ

• Reports changes in muscle tension via 1b axons

• Uses a coxntraction to inhibit further contractions

  • For activities that require control/steady force

• Reverse myostatic reflex - relaxes a muscle in response to increased muscle tension

Baroreceptor Reflex

Negative feedback - low BP → ↓ parasympathetic & ↑ sympathetic → ↑ cardiac output