Day 3

Neurotransmitter released from the PRE side diffuses across the synaptic cleft and binds to a receptor on the postsynaptic membrane

POST synapse step 1: NT crosses the cleft

Binding triggers either the fast ionotropic pathway or the slower metabotropic pathway

POST synapse step 2: Receptor type decides the pathway

The receptor is itself the channel and opens immediately; Na+ in produces an EPSP, K+ out produces an IPSP

POST synapse step 3: Ionotropic pathway

The receptor activates a G-protein, then an effector, then a second messenger (cAMP), which can change the membrane, change the cytosol, or reach the nucleus for gene transcription

POST synapse step 4: Metabotropic pathway

The resulting EPSP or IPSP spreads toward the soma/axon hillock, where it is added into summation with every other PSP the neuron is receiving

POST synapse step 5: PSP travels onward

AP arrives at the presynaptic terminal

Synapse step 1: Depolarization

Voltage-Gated Ca2+ Channel opens; Ca2+ is in high concentration outside, so it rapidly flows in (high to low); this influx triggers neurotransmitter release

Presynapse step 2

Calcium tells vesicles to dock at the membrane; vesicles move and attach (VMAT = vesicular transporter that packages NT into vesicles)

Synapse step 3: VMAT

The vesicle membrane fuses with the presynaptic membrane and releases neurotransmitter into the synaptic cleft ("exiting")

Synapse step 4: Exocytosis

Monoamine oxidase, an enzyme that breaks down neurotransmitter outside the vesicles; NT is safe from MAO while stored inside vesicles

Synapse step 5: MAO

Endocytosis

Vesicle membrane is recycled/refilled with neurotransmitter

Reuptake

Transporters bring released neurotransmitter back up into the presynaptic cell, removing it from the cleft

Made by ribosomes in the rough ER, in the soma/cell body

Where are neurotransmitters synthesized?

Packaged into vesicles by the Golgi apparatus, in the soma/cell body

Where are neurotransmitters packaged?

Via microtubules

HOw are NT transported

Autoreceptor

A presynaptic receptor that continuously monitors neurotransmitter release and tells the cell to stop releasing more; it is inhibitory

Autoreceptor mechanism

Blocks VGCC and opens K+ channels, both of which reduce further neurotransmitter release

Ionotropic receptor

A fast, ligand-gated ion channel; neurotransmitter binds and the receptor itself opens immediately as a pore, letting ions move straight through (Na+ in = EPSP, K+ out = IPSP)

Metabotropic receptor

A slower, longer-lasting receptor type; neurotransmitter binds and activates the receptor, but it does not form a channel itself; works indirectly through G-proteins and second messengers

Open or close ion channels

Metabotropic possibility 1: Changes at the membrane

Deactivate proteins, e.g. via cAMP, a second messenger

Metabotropic possibility 2: Changes in the cytosol

Translocation leads to gene transcription, making new proteins and inserting them into the cell

Metabotropic possibility 3: Interact in the nucleus

Agonist

A drug that mimics what normally happens

Antagonist

A drug that blocks what normally happens

Autoreceptor antagonist effect on NT

Increase in NT (blocks the "stop releasing" signal)

MAO agonist effect on NT

Decrease in NT (more breakdown of NT)

Transporter antagonist effect on NT

Increase in NT (blocks reuptake, so NT stays in the cleft longer)

Drug reasoning tip

Ask whether the drug helps or blocks NT release, breakdown, or reuptake, then decide increase vs. decrease

Caffeine/neural adaptation example

Caffeine constricts blood vessels; with repeated use, the brain predicts this effect and compensates in advance, which is why skipping a usual dose causes withdrawal-like side effects

EEG (Electroencephalography)

Electrodes on the scalp record overall electrical activity of neurons; not the most accurate for location, but non-invasive and shows activity of groups of neurons

CT Scanner

A rotating X-ray source and detectors build a computer image of brain structure; not the most accurate scan for anatomy

PET Scan

Person does a cognitive task while the scanner tracks uptake of radioactive glucose (2-DG) in active cells; shows brain activity in real time

MRI (structure)

Uses magnetic fields and radiofrequency pulses on hydrogen atoms; when the RF field turns off, released energy is measured to build a structural brain image without damaging tissue

fMRI (function)

Measures increased oxygen carried by hemoglobin in blood as a sign of more neural activity; spatial resolution 1-2 mm, temporal resolution about 1 second