BioPsych Chapter 1

Basic Overview of Neurons

  • Electrically charged
  • ^^Synapse^^: the functional zone
    • How neurons communicate
    • Neurons are NOT connected continuously (like wires) but separated by functional space through which they communicate.

Parts of the Neuron

  • ^^Soma^^ (aka the cell body or perikaryon)
    • Stores genetic information and genes
  • Neurites (aka the ^^Dendrites / Axon^^)
    • Cellular fibers emerging from the soma
    • ==Dendrites: “recieving”==
    • ==Receives chemical info from other neurons==
    • ==Axons: “output”==
    • ==Relays info to other neurons==
  • ^^Presyanptic Terminals^^ (aka boutons)
    • ==Metabolism==
  • Contains synaptic vesicles that contain ^^neurotransmitters^^ (neurochemicals essential for neuronal function)

 

                                                         Myelin sheath is a protein

Neuronal Action at the Synapse

^^Neurotransmitter receptors:^^ specialized proteins in the membrane of post-synaptic neuron

  • Neurotransmitter released from pre-synaptic terminal → binds to neurotransmitter receptor → opens pore for charged ions to enter/exit neuron → changes electrical charge of neuron
    • ^^Inhibits:^^ cell body loses ions (cell becomes negatively charged)
    • ^^Excites:^^ cell body gains ions (cell becomes positively charged)
    • Example of Ionic neurotransmitter receptor type
      • SSRIs and SSRNIs

^^Neurotransmitter Re-uptake pumps:^^ specialized proteins on presynaptic membrane

  • Bind and transport back in the pre-synaptic terminal
  • Purpose: breaking down and packaging
  • Example: SSRIs

 

Type of Neurons

How are they characterized?

  • \   # of Neurites from soma

Classification

  • Unipolar (One neurite)
  • Bipolar (Two neurites)
  • Multipolar (Three neurites)

 

Neural Function

Original “Law of Dynamic Polarization” : Neuronal function from neuron structure (Ramon Cajal)

  • Axo-dendritic connection/synapses (A)
  • Info flows from dendrite → soma → axon → dendrite

*Revised “Law of Dynamic Polarization”: Info flows from presynaptic cell to post synaptic cell with respect to specific synapse \n *

 

  • Axo-somatic synapses - Synapse on cell body (B)
  • Axo-axonic synapses - Synapse at beginning of axon (C)
  • Axo-synaptic synapses - presynaptic terminals connect w/ one another (D)

 

The Neuronal Membrane

Controls the neuronal function and separates the intracellular environment from the extracellular environment.

Polar/Nonpolar

Polar: have an electrical charge

  • Water (+ charge on H, - charge on O)
    • Like charges repel

Nonpolar: don’t have an electrical charge

  • Organic molecules (contains carbon)
  • Grease, oil, lipids(fats)
  • Can’t interact with polar molecules (I.e. water); therefore not soluble
    • Phospholipids: phosphate group acquired by nonpolar molecules WHEN COMBINED
Phospholipids
  • The “head”: the phosphate group, charged (polar)
    • Hydrophilic region
  • The “tail”: the hydrocarbon group, not charged (nonpolar)
    • Hydrophobic region

When together, this is a phospholipid.

 

The cell membrane
  • Made up of the phospholipids
  • ^^Lipid bilayer^^
    • Hydrocarbon group (tails) on the inside, phosphate group on the outside
    • Inside and outside of the membrane is charged, and inside is uncharged.
  • ^^Amphipathic^^
    • Both hydrophobic and hydrophilic regions
Fluid Mosaic
  • Bilayer’s hydrophobic interior stops charged ions from getting in and out of the cell, so,
  • ^^Transmembrane proteins^^^^:^^ channels that allow ions to move in and out of the cell
    • aka channels and pumps
    • There are specified channels for each ion (sodium, hydrogen, chlorine, etc)
    • thus, changing the charge of the cell
    • These channels and pumps are why we call the membrane a fluid mosaic.

Genetics Overview

DNA (genes) is transcribed into RNA (genetic intermediary) that is translated into Protein (the functional molecule in a cell)
  • DNA (Deoxyribonucleic acid)
    • double-stranded genetic sequence
    • synthesis of RNA
  • RNA (ribonucleic acid)
    • single-stranded copy of DNA
    • ^^Transcription^^: production of an RNA copy of DNA
    • occurs in the nucleus
    • messenger RNA (mRNA) codes for specific amino acid sequence (protein)
      • mRNA exists the nucleus and travels to the cytoplasm of cell.
  • Protein
    • mRNA is the synthesis of proteins
    • Sequences of amino acids
    • 3 amino acids make one protein
    • amino acids from transcription(DNA to RNA) is then translated to a protein.
    • Translation: assembly of amino acids in a specific sequence

Chemicals and Proteins Important for Neuronal Function

Chemicals

Neurotransmitters: Chemical molecules released from neurons that act as chemical signals between neurons

  • Classical neurotransmitters: small chemical molecules
    • Norephrine (Noradrenaline): Concentration
    • Gaba: Calming
    • Dopamine: Pleasure
    • Glutamate: memory (excitation), most common
    • Serotonin: mood (happiness)
    • Acetylcholine: learning
  • Peptide neurotransmitters: short peptides (small proteins)
    • Endorphins
    • Often works with classical neurotransmitters
    • Can be 5 - 50 amino acids
Proteins

Ion channels/pumps

  • proteins in the cell membrane that move ions (mainly salt [NaCl] and K] in and out of the cell

Neurotransmitter receptors

  • proteins in the post-synaptic cells that bind to neurotransmitters released in the synapse
  • The neurotransmitter binds to the receptor → opens a pore for charged ions (to enter/exit) → changes the charge post-synaptic neuron.
  • Types of receptors
    • ^^Metabotropic^^
    • The neurotransmitter binds to receptor → activates protein (aka signaling molecule) → ion channel opens/closes
    • ^^Ionotropic^^
    • The neurotransmitter binds to ion channel → channel opens
      • ion channel has its own neurotransmitter (ligand) bonding site

Types of Ligands for Neurotransmitter Receptors

Overview
  • Continuum of Efficacy
    • Neurotransmitters act by rapidly bind/activate receptors & then release and deactivate a neurotransmitter receptor
    • Reuse after function is completed
  • Neurotransmitters have
    • ^^Affinity^^ (how fast and strong a ligand is)
    • ^^Potency^^ (how biologically effective a ligand is once bonded)
    • There are varying levels of both (high affinity and low potency)
    • Properties of the receptors determine the properties of the transmitters
Types of Ligands

Remember: ligands are what bind to the receptors

^^Agonist^^

  • A ligand that binds to a receptor and activates it biologically
  • varying levels of affinity and potency
  • Endogenous

^^Antagonist^^

  • ligands that bind to a receptor and do not activate it biologically
  • Typically have high affinity and zero potency
    • So receptor is blocked from functioning
  • all antagonists are exogenous: foreign substances
    • Toxins and venoms
    • Opioids

Allosteric modifiers

  • helps naturally occurring ligand increase likelihood of receptor-ligand binding
    • In humans, helps agonists
  • Binds to a different location that agonist and antagonists
  • Benzodiazepines

Excitation and inhibition are properties of the receptor, not the neurotransmitter/ligand

 

The Concept of Neuromodulation

Peptide transmitters

  • Are often co-transmitters and are released with small chemical neurotransmitters such as dopamine/norepinephrine.
    • These often act at allosteric sites
    • Act as neuromodulators: a substance that binds to a receptor at a different location than the neurotransmitter itself
  • Increases affinity of the receptor to bind to the neurotransmitter

Neurotransmitters

Acetylcholine
  1. Synthesized in pre-synaptic terminal by ^^cholineactyltransferase (ChAT)^^.
    • Enzyme that transfers acetyal group to choline.
  2. Fuses acetate (from Acetyl-CoA) and choline together
  3. Packed in vesicle and sent out

To terminate post-synaptic ACh activity

  • Desensitization: respectors become less responsive to presence of ACh
  • Diffusion: ACh out of the synapse
  • Breakdown: of transmitter molecules
    • For ACh, use of AChE(acetylcholinesterase)
    • Makes sure we don’t have too much Acetyl CoA in our system (to breathe)
  • Drugs
    • Physostigmine: naturally occurring drug that blocks AChE
    • gets more Acetyl-CoA function
    • Insecticides: manmade AChE blockers

Neuromuscular junction

  • via nicotinic ACh receptors (stimulant)
Gamma-aminobutyric Acid (GABA)

Produces neural inhibition (most common)

  1. Synthesized from glutamate
  2. Glutamic acid decarboxylase (GAD) converts glutamate to GABA

GABA transaminase: recycles GABA back to glutamate for re-uptake and use

GABA A receptors

  • Ionotropic receptors, Cl- channels
    • cell becomes more negative
  • at least 2 allosteric bonding sites
    • when bound increases the ability of the receptor to bind to neurotransmitter
    • Action seen in benzodiazepines (anti-anxiety) and barbiturates (depressants)
      • doesn’t produce inhibition itself, but increase affinity for GABA receptor for GABA.
    • increase ability of GABA a receptors to bind GABA

In the Brain

Majority of the synapses in the brain are GABA-containing

  • Many use presynaptic inhibition (via axo-synaptic contacts)
    • GABA blocks the synaptic terminal from releasing neurotransmitters
  • GABA antagonists (receptor blockers) produce excitation
    • blocking inhibition = excitatory effects
    • can cause seizures
  • Epilepsy: loss of GABA producing neurons
    • treated with GABA simulating drugs
Glutamate

Produces neural excitation, ionotropic receptors.

  • Associated with memory and learning, the big daddy
  • Long term effects on cell function

Types of receptors

  • Sodium receptors
  • AMPA: most active
  • Kainate
    • Both cause excitation because of positive sodium ion.
  • Sodium AND calcium receptors
    • NMDA
    • Excitation due to positive sodium and calcium ions.
Glycine

Amino acid for inhibition

  • in spinal cord (used instead of GABA)
    • Strychnine
    • poison, glycine antagonist causing spinal seizures
Biogenic Amines

Have different amine groups(ring structure) attached

  • Synthesized by tyrosine or tryptophan

Types of receptors

  • Dopamine(DA) and Norepinephrine(NE)
    • share core structure(catechol ring group) and nitrogen-containing side group(amine)
    • Synthesis
    • From Tryosine → DOPA (one hydroxl group to two) → Dopamine (Loss of COOH [carboxyl acid]) → Norepinephrine (adding oxygen to one hydrogen)

Seotonin

  • Small molecule transmitter
  • core structure (indole ring) and nitrogen containing side group (amine)
  • Synthesis
    • L-Tryptophan → L-5-Hydroxtryptophan aka 5-HTP (added HO group) → serotonin (loss of carboxyl acid)

 

Peptide Transmitters

A short chain of amino acids

Can act one of two ways

  • Peptide transmitters: released in brain as neurochemical signal between neurons
  • Peptide hormones: released from brain into the blood stream to act as neurochemicla signal between brain and body

How it is synthesized

  • synthesized as large proteins to small “active” peptides →packaged into vesicles in cell body → ^^orhtograde axoplasmic transport^^ (sent down axon to synaptic terminal)

Once released, diffuse away from sunapse or broken down by enzymes (^^proteolysis^^)

Act at low concentrations for a long time

  • Because they require a lot of energy (metabolically expensive)
  • Therefore, they are called neuromodulators

Examples

  • endorphins, enkephalins, oxytocin & vaspressin

Other important proteins

Structural proteins (actin, tubulin and elastin)

  • Hold cells & keeps them In place.
  • Determines the shape and movement of cell

Enzymes

  • A catalyst that is a protein
    • Creating products from building blocks
    • Can be catabolic or anabolic!

The Active Neuron

Axoplasmic Transport

  • Transport of proteins to distant location in the neuron.
  • Moving between cell body and axon.
    • Orthograde/anterograde transport
    • Away from the cell body (to neutries)
    • For release
    • Retrograde transport
    • Toward the cell body (from neurites)
    • For degradation

Neuronal Release

Exocytosis

  • Fusion of the synaptic vesicle with the plasma membrane
    • peptide transmitters of neurotransmitters are dumped into extracellular space (synapse)
    • Fusing with terminal membrane and releasing its prescense
    • Calcium helps vesicle proteins to bind with the membrane, bringing the vesicle close enough the fuse

 

Endocytosis

  • Piece of the membrane that pinches back to form a new vesicle
    • In order to maintain size

 

Neuronal Development/Aging

Neurons use the exocytosis and endocytosis to grow, develop and prune.

  • Neuronal growth
    • Neuron sends out neural processes
    • axon growth
    • exo > endo
    • axon from one neuron grow and connect with another neuron to form synapse
  • Neuronal pruning
    • Neural processes (axons) withdraw
    • exo > endo
    • axon from one neuron withdraws connection with another
  • Mature Synapse
    • stable associations between neurons
    • endo = exo

Chemoaffinity Hypothesis

  • How neurites find their way through development
  • Chemical signals (trophic factors) - proteins that help nerve cells develop and recognize each other are exchanged between potential synaptic partners
    • Grow cone
    • Tip of growing neuronal axon
    • Withdrawl and approach cycles
    • When correct synaptic partner is found
      • filopodia flatten out
      • presynaptic and post synaptic densities appear

Neuroplasticity

@ mature synapse, # of postsynaptic receptors in membrane can be increased (up-regulated) or decreased(down-regulated)

  • Based on amount of neurotransmitter released and received by receptors on the postsynaptic cell.
    • ^^Up regulation:^^ little neurotransmitters, lots of receptors
    • presyn: decrease trophic influence
    • postsyn: increase receptor number
    • Problem with up-regulation: can cause hypersensitivity
    • Decrease in neurotransmitter influence → starves post synp cell → post synp produces more receptors and becomes sensitive to the remaining neurotransmitter around it
    • Example: phantom leg pain
    • ^^Down regulation:^^ lots of neurotransmitters, not a lot of receptors
    • presyn: increase in trophic influence(neurotransmitter)
    • postsyn: decrease in receptor
    • Problem with down-regulation: can cause desensitization
      • Too much neurotransmitter can cause the post syn cell to feel overwhelmed → post synp cell decreases receptors and becomes less sensitive to the presence of neurotransmitters
      • May or may not change back to normal
      • Seen in drug addiction
      • Too much, so I change

Regeneration

Schwann Cells
  • Glial cells that myelinate neurons are
    • Myelinate a single neuronal axon
    • when axon is damaged, schwann cells form a guidance tube to guide the regnerating end of the axon to the target end of the axon.
    • In PNS
    • 1 cell body with one axon.
Oligodendrocyte
  • Glial cells that myelinate neurons
    • Myelinates multiple axons
    • Axon is damaged → oligodendrocytes fail to respond → withdraws remaining support → axon degenerates and damage is permanent.
    • There’s not enough space in the brain for other cells, which is why oligodendrocytes are used.
    • In the CNS
    • I.e. spinal cord injury
    • 1 cell body with many axons