biological psychology lectures 5-8

dendrotoxin

• a toxin from snakes

• blocks potassium channels

tetrodotoxin

• a toxin from pufferfish

• blocks sodium channels

what is the benefit of these toxins?

• treatment of diseases like MS and spinal cord injuries

• reduced risk of developing Parkinsons

what is the uploaded graph telling us?

what happens to the membrane during AP

what is the uploaded graph telling us?

• what happens to the flow of ions during a change in membrane potential

threshold definition

the rate of sodium entry and potassium exit into neurons

refractory period

• the time from the onset of AP and when it can fire again

absolute refractory period

nothing will happen, no matter how much current is injected

what determines how the charge flows?

• leak out of the cell (Rm)

• flow through the cytoplasm (Ri)

• stored by the membrane(Cm)

does action potential require active and passive flow? what is the difference?

it does require both

• active is the opening of gated ion channels

• active is all or none

• passive is movement along the axon

• passive decays over distance

what is conduction velocity?

the speed at which APs travel along a nerve fiber

what 3 properties does it rely on?

• membrane resistance

  • leakiness

• membrane capacity

  • charge needed to activate AP

• internal resistance

  • things inside the cell

what is the vertebrae solution to increasing AP velocity?

myelination

this covers the holes and keeps the charge inside

myelin

• made by glial cells

• increases the conduction velocity

  • increases membrane resistance

  • decreases membrane capacity

are myelin sheets continuous?

No

the spaces between are called nodes of Ranvier

sodium channels cluster in the nodes

saltatory conduction

• the action potential jumps from node to node

• the current is regenerated at each node, forcing it to continue along

Multiple Sclerosis

• a chronic inflammatiory CNS disease

• a demyelinating disease

• affects the brain, optic nerves and spinal cord

Schwann Cells

glia that provide the myelin wrap for PNS

oligodendrocytes

glia that provide myelin wrap for the CNS

What happens in MS?

• T-cells and macrophages attack the myelin sheath

• they do this through the blood-brain-barrier

What happens to the BBB in MS?

• normally, the CNS is inaccessible for immune attacking agents

• however, this barrier is broken down, allowing said immune attacking agents to cross over and attack the myelin sheaths

what is the BBB?

• blood-brain barrier

• a collection of cells that control the passage of blood to the CNS

• serves as a protective layer from infection

how does MS affect the CNS?

• it interrupts the AP conduction

• exposed axons can sever, leading to permanent damage

what is excitotoxicity?

• a process that releases glutamate

• this causes an excess calcium influx

• the excess Ca++ triggers cell death

MS demographics

• there are around 200 cases diagnosed weekly

• 1 million individuals affected in the US

• diagnoses between ages 20-50

• affects those ages 25-35

MS region of origin globally

• the highest risk areas are Canada, San Marino, Denmark

• in the US

  • North: 110-140 cases for every 100,000 people

  • South: 57-78 cases for every 100,000 people

genetic risk for MS

• up to 19% of patients have affected relatives

  • monozygotic twins: 25-30%

  • dizygotic twins: 3-4.5%

  • child: 1.9%

  • sibling:0.9%

environmental risks

• sunlight

• diet

• life experiences

MS types

• benign

• relapsin-remitting

  • symptoms last days to weeks, followed by symptom free periods

• secondary progressive

  • follows the schedule of relapsing-remitting

  • each episode leaves some type of permanent damage

• primary progressive

  • the slow worsening of symptoms

  • the symptoms never truly get better

symptoms

• optic nerve inflammation: 14-29% incidence

• poor balance (ataxia): 2-18%

• dizziness (vertigo): 2-9%

• muscle weakness: 10-40%

• double vision (diplopia): 8-18%

• bladder dysfunction:0-14%

• pain: 21-40%

• sensory loss: 13-39%

how is MS diagnosed?

• neurological exam

• MRI scans

  • demyelination shows up as bright lesions

  • white lesions indicate fresh inflammation

• lumbar puncture

  • tests CSF’

• evoked potential tests

  • an MS brain response less actively to stimulation

  • the decreased activity reveals demyelination

• blood tests

lesions in different areas

• temporal lobe

  • cognitive impairments

  • depression

• right optic nerve

  • loss of vision

  • reduced visual activity

• brainstem

  • clumsiness, poor balance

  • impaired speech

• cervical spinal cord

  • weakness, stiffness

  • painful muscle spasms

treatment and management of MS

• drug therapy

  • immunosuppressants

  • calcium channel blockers

  • immunomodulating drugs

    • the drugs treat new attacks and prevent future ones

    • they slow/prevent disease progression

    • treat chronic symptoms

• physical therapy

• psychosocial support

what is the uploaded image showing us?

how MS is monitored via MRI scans

what is the axon hillock?

• the site of AP initiation

• the axon is far from the terminal

synapses

• chemical synaptic transmission

  • neurotransmitter

• electrical synaptic transmission

  • gap junction

what is the gap junction?

• good for

  • synchronization of networks

  • coordinated hormone release

  • coordinated breathing

  • fast escape behaviors (in animals)

connexins

• channels that form a pore to connect cytoplasm

• this allows direct ion flow

Loewi’s experiment

• demonstrates chemical neurotransmission

• before 1921, people believes the nervous system operated solely on electrical signaling

chemical synapse

presynapse: site of release

synaptic cleft: the space between pre and post sites

synaptic vesicle: stores neurotransmitters

postsynaptic density: opposite the release site

stimulus secretion coupling

• depolarization by an AP opens voltage gated calcium channels of the axonal terminal

• in simple terms, a cell translates external signals to release stored products

chemical synaptic transmission

• Ca++ dependent neurotransmitter release

  • AP travels to terminal

  • AP depolarizes axon terminal

  • depolarization opens the Ca++ channels

  • Ca++ influx

  • triggers neurotransmitter release

    • this is vesicle fusion

vesicle fusion

• vesicle docks

• the entering Ca++ binds to synaptotagmine (main calcium sensor for neurotransmitter release)

• SNARE complexes form to pull membranes together

• Ca++ bounds synaptotagmine catalyzes fusion

endogenous ligands

• made inside

• neurotransmitters

• hormones

exogenous ligands

• made outside

• drugs

• environmental toxins

agonist vs antagonist

• agonist activates receptor and produces a response

• antagonist blocks receptor and suppresses a reaction

affinity vs efficacy vs potency

• affinity is how well a ligand binds to a receptor

• efficacy is the ability of a drug to produce an effect

• potency is a measure of the amount of ligand needed to make an effect of a certain magnitude

what are the two major receptor classes?

• ionotropic

  • neurotransmitter gated ion channels

• metabotropic

  • G. proteins coupled receptors

neuromuscular junction

• a specialized chemical synapse between motor neurons and skeletal muscle cells

• motor neurons released ACh (acetylcholine which encourages neurons to fire)

what is an NAChR

• an ACh gated receptor

  • ACh bimds

  • the Na+ channel opens

  • the membrane depolarizes

• nicotonic acetylcholine receptors

  • contain 5 subunits

what breaks down the ACh signal in the synaptic cleft?

AChE (acetylcholinesterase)

Aldicarb

• a neurotoxin

• used as a pesticide

• blocks AChE

Myasthenia Gravis

• an autoimmune disease that causes muscle weakness

• symptoms

  • eyelid dropping

  • impaired speech

  • difficulty swallowing

  • double vision

  • easily fatigued

  • waddling gait

• antibodies bind to the post-synaptic ACh receptors on the motor end plate

• leads to receptor inflammation/desctruction

• motor end plate atrophy

MG treatment

• cholinesterase inhibitors

• immunosuppressants

• corticosteroids

glutamate

• excitatory neurotransmitter in the CNS

• its receptors are glutamate gated Na+ channels

EPSP process

• glutamate binds to R

• Na+ channel opens

• depolarization

EPSP vs IPSP

• EPSP is an excitatory post synaptic potential

• depolarizes the neuron

• this makes it more likely to fire AP

• IPSP is an inhibitory post synaptic potential

• IPSP hyperpolarizes the neuron

• this makes it less likely to fire AP

IPSP process

• GABA binds to R

  • GABA is an inhibitory neurotransmitter

  • gamma-aminobutyric acid

• Cl- (chloride) channel opens

• hyperpolarization

axodendritic vs axosomatic

• axodendritic connects the axon to the dendrite

• axosomatic connects the axon to the soma (cell body)

what is the type of PSP dependent on?

• the type of channel present in the post synapse

spatial summation

• PSPs arriving on different dendrites or from different axons

• multiple inputs at the same time

temporal summation

• they arrive at slightly different times

learning

• the acquisition of new information and knowledge

• a behavior change based on experience

memory

• the retention of information

• ability to store and recall experiences

what are the two types of memory?

• implicit/procedural

  • skills and behaviors

  • require practice

  • performed without conscious recall

• declarative

  • facts and events

  • consciously recalled

  • easy come, easy go as Dr. Ingemi says lmao

synaptic facilitation

• enhancement of sensory neuron

• motor neuron synapses

• increase in neurotransmitter release

• the cause of sensitization

sensitization

• an enhanced response to a stimulus

synaptic depression

• weakening of the sensory neuron

• motor neuron synapses

• decrease in neurotransmitter release

• this causes habituation

habituation

the gradual decrease of a response due to repeated exposure

Hebb’s Postulate

• coordinated activity of the pre and post synaptic neuron strengthens the synapse as a whole

• synchronized=strengthened

• not synchronized=not strengthened

what are the two types of glutamate receptors?

• AMPA

  • amino-3-hydroxy-5-methyl-4-izoxazole proplonic acid

• NMDA

  • N-methyl-D-aspartate

  • selective to Na+, K+, and Ca++

AMPA receptors

• bind glutamate

• channel opens

• Na+ influx

• depolarization

• EPSP

NMDA receptors

• bind glutamate

• nothing happens

what happens during high frequency stimulation for AMPA receptors?

• bind glutamate

• more channels open

• large Na+ influx

• strong depolarization

• big EPSP

what happens during high frequency stimulation for NMDA receptors?

• bind glutamate + strong depolarization

• channel opens

• influx of Na+ and Ca++

why is the magnesium block relevant?

• at resting potential, the pore of the NMDA receptors is blocked by magnetism ions

• upon DP, the magnesium ions are removed, the channel can now pass current

what happens when Ca++ enters through NMDA receptors?

• activates long-lasting changes to the AMPA receptors

  • the number of receptors increases

  • the existing receptors increase their permeability

    • this creates a larger EPSP

what is long term potentiation?

• the long term strengthening of synaptic connections

• however, it requires an NMDA receptors