Neurotransmission and Synaptic Potentials

Main steps of neurotransmitter release into the synaptic cleft:

Action potential arrives at the axon terminal

Voltage-gated calcium channels open

Calcium influx occurs

Synaptic vesicles fuse with the presynaptic membrane

Neurotransmitters are released into the synaptic cleft

Key differences between ionotropic and metabotropic receptors:

Ionotropic receptors:

Directly open ion channels upon neurotransmitter binding

Lead to rapid postsynaptic effects

Act like "direct-acting" channels

Metabotropic receptors:

Activate G proteins, triggering intracellular signaling cascades

Result in slower, longer-lasting postsynaptic effects

Act through intermediaries

Mechanisms for excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs):

EPSPs:

Neurotransmitter binds to receptors, opening channels for positive ions (e.g., sodium)

Influx of positive ions causes depolarization

IPSPs:

Influx of negative ions (e.g., chloride) causes hyperpolarization

Decreases the likelihood of action potential firing

Activation of different ligand-gated ion channels depends on the neurotransmitter

Properties of graded potentials:

Temporary changes in membrane potential that vary in magnitude

Not "all-or-none" like action potentials

Can be depolarizing (excitatory) or hyperpolarizing (inhibitory)

Decrease in strength as they spread from the stimulation site due to current leak

Localized to the area of stimulation

Size is proportional to stimulus intensity

Generated by opening of ligand-gated ion channels

Occur in dendrites and cell bodies of neurons

Summation can trigger an action potential if the threshold is reached at the axon hillock

Integration of signals from different synapses by postsynaptic potentials (EPSPs and IPSPs):

Occurs through "summation" at the axon hillock

Electrical changes from multiple EPSPs and IPSPs are added together

Determines whether the neuron fires an action potential

If the combined potential surpasses the threshold, an action potential is triggered

Role of voltage-gated calcium channels in neurotransmission:

Main pathway for calcium ions (Ca2+) to enter the presynaptic terminal

Triggers fusion of synaptic vesicles with the cell membrane

Allows neurotransmitters to be released into the synaptic cleft

Termination of neurotransmitters in the synaptic cleft:

Acetylcholine:

Terminated by acetylcholinesterase (AChE)

AChE transforms acetylcholine into choline and acetate

Choline and acetate are transported back into the cell

Glutamate:

Terminated by reuptake, mainly by astrocytes

Astrocytes convert glutamate to glutamine using glutamine synthetase

Glutamine is transported back to the neuron

GABA:

Terminated by reuptake by neurons and astrocytes

GABA is converted back to glutamate by GABA aminotransferase (GABA-T)

Role of autoreceptors in neurotransmission:

Act as a feedback system for neurons

Detect the amount of neurotransmitters released from the presynaptic neuron

Cause a decrease in the release of neurotransmitters

Regulate the release of neurotransmitters

Blocking voltage-gated calcium channels affects neurotransmitter release and postsynaptic potentials:

Blocking voltage-gated calcium channels in the presynaptic neuron would prevent calcium from entering the presynaptic terminal, thus preventing neurotransmitter release

Impaired acetylcholinesterase function on synaptic transmission at a neuromuscular junction:

Impaired acetylcholinesterase function leads to prolonged muscle contractions

Buildup of acetylcholine in the synaptic cleft because the enzyme is unable to effectively break down the neurotransmitter

Overstimulation of muscle receptors, leading to potential muscle weakness or paralysis

Mechanism allowing a postsynaptic neuron to reach threshold and fire:

Summation is the mechanism

Combined effect of subthreshold EPSPs arriving at different synapses nearly simultaneously can add up to reach the threshold potential and initiate an action potential

Can occur through:

Spatial summation (from different synapses)

Temporal summation (from the same synapse firing rapidly in succession)

Effect of a toxin blocking neurotransmitter reuptake:

Prolongs the neurotransmitter's effect on the postsynaptic neuron

Increases the amount of time the neurotransmitter remains in the synaptic cleft

Leads to amplified synaptic transmission involving that neurotransmitter

Otto Loewi's contribution to understanding chemical synapses

He was the first to convincingly show that communication across synapses occurs via chemical means, not electrical.

He did experiments using two frog hearts, one connected to the vagus nerve, in separate chambers.

Electrical stimulation of the vagus nerve on heart #1 caused it to slow down, and, after a delay, heart #2 also slowed down via fluid exchange.

Loewi's experiment suggested that electrical stimulation caused the release of a chemical (now known as acetylcholine) that affected the second heart.

Phrenology

The study of bumps on the skull and their relation to a person's personality and talent

Has been debunked due to parts of the brain working together

There is no accurate correlation between bumps on the skull and aspects of personality and talent

Methods used to study brain function:

Lobotomies:

Involve the removal or destruction of parts of the brain (now obsolete)

Electroencephalograph (EEG):

Records electrical activity of the brain

CT and MRI scans:

Produce 3D images of the brain

fMRI:

Examines function by restricting blood flow to different areas of the brain

Diffusion Tensor Imaging:

Detects white matter in the brain

PET scans:

Use radioactive chemicals to monitor brain activity

Brain Stimulation:

Involves stimulating specific areas of the brain

Purpose and decline of Lobotomies:

Initially used to treat schizophrenia by making psychotic symptoms more manageable

Eventually became obsolete due to the high risk of complications

The introduction of chlorpromazine, an antipsychotic drug, contributed to their decline

Dr. Walter Jackson Freeman II

Was an American physician specialized in lobotomies.

Freeman popularized transorbital lobotomies, which were quick procedures that did not require anesthesia or a neurosurgeon.

Though lobotomies were eventually discredited, and he was banned from doing surgeries, his work significantly impacted the field of psychosurgery and the treatment of mental illness at the time.

How EEG, CT scans, and MRI work and information they provide:

EEG:

Records electrical activity of the cortex (nothing below it)

Detects activity of large groups of neurons active at the same time

Primarily detects postsynaptic potentials

CT Scan:

Uses x-rays to generate 3D images of the brain

MRI:

Uses magnetic fields to create a more detailed view of the brain

Purpose of fMRI and PET scans in localizing brain function:

These scans help see what behaviors cause certain areas of the brain to peak

An fMRI shows changes in blood flow during cocaine cravings

These techniques allow us to gain a better understanding of the relationship between the brain and certain behaviors, such as addiction

Gray matter vs. white matter:

Gray matter:

High concentrations of cell bodies and dendrites

Responsible for information processing

White matter:

Contains long, myelinated axonal fibers

Projects to different brain regions to transmit messages

Main components of the somatic nervous system:

Afferent nerves:

Process sensory information

Efferent nerves:

Process motor signals

Four main regions:

Cervical

Thoracic

Lumbar

Sacral

Four major regions of the CNS and five subregions of the brain:

4 major regions of the CNS:

Forebrain

Midbrain

Hindbrain

Spinal cord

5 subregions of the brain:

Telencephalon

Diencephalon

Mesencephalon

Metencephalon

Myelencephalon

Main structures and functions associated with the hindbrain:

Myelencephalon:

Contains the medulla oblongata, which has two general regions known as pyramid and olive.

Controls basic life functions such as breathing, heart rate, blood pressure, salivation, and vomiting

Metencephalon:

Contains the cerebellum, which is associated with development and coordination of movement, balance, gating, and somatosensory information such as textures

Connected via the Pons, the bridge for many sensory axons passing from one side to the other side of the brain

Location and function of the substantia nigra:

Located in the mesencephalon, part of the midbrain

Dopamine-producing neurons

Correlated with movement, muscle tone, and posture

Degeneration leads to Parkinson’s disease

The blood-brain barrier

Semipermeable membrane separating blood circulating in the brain from the extracellular fluid of the brain tissue.

It protects the brain from harmful substances while allowing for nutrients and oxygen to come through.

Uncharged small molecules (CO2, O2) and lipid-soluble substances can pass into the brain freely.

Most other chemicals need a transport system into the brain.

Broca's area in the frontal lobe:

Stroke which affected Broca’s’ area results in speech/language difficulties

Damage to the dorsal root ganglion:

Would cause sensory loss such as numbness, tingling, and lack of ability to feel pain, pressure, touch, and temperature

Difficulties with balance and coordination:

Likely experiencing complications in their cerebellum, located within the metencephalon

Toxin targeting and destroying astrocytes in the brain:

Since astrocytes are responsible for forming tight junctions which make up the blood-brain barrier, this would severely hinder the blood brain barrier

Harmful substances may pass into the brain, causing widespread neurological dysfunction

Superior and inferior colliculi contribution to sensory processing:

The superior colliculi relay visual information

The inferior colliculi relay auditory information

Main functions of the thalamus:

Relay station of the brain

Responsible for receiving sensory information and directing it to the cerebral cortex

Plays a role in sleep, wakefulness, consciousness, learning, and memory

Role of the ventricular system and cerebrospinal fluid (CSF):

The ventricular system produces and circulates cerebrospinal fluid (CSF)

Which acts as a protective cushion around the central nervous system (CNS), safeguarding it from impact

Provides essential nutrients by constantly bathing the brain and spinal cord while removing waste

Criteria for a chemical to be classified as a neurotransmitter:

Must be synthesized in the neuron

Must be present in the presynaptic

Be released when an action potential reaches the terminals

Be recognized by specific receptors causing a change in the postsynaptic cell

Must be inactivated

Classification of neurotransmitters based on size:

Small-molecule neurotransmitters

Large-molecule neurotransmitters (neuropeptide transmitters)

Gaseous neurotransmitters (nitric oxide)

Synthesis process for small-molecule neurotransmitters:

Enzymes for synthesis are synthesized in the soma

Golgi apparatus packages the enzyme and transports it to the terminal

Precursors are taken up at the terminal button

Newly synthesized neurotransmitter is transported to a vesicle

Released via exocytosis

Synthesis process for neuropeptide neurotransmitters:

Polypeptides and enzymes for synthesis are synthesized in the soma

Golgi apparatus packages the enzyme and polypeptide and transports it to the terminals

Enzymes cut polypeptides to produce a smaller peptide that functions as a neurotransmitter

Newly synthesized neurotransmitter is transported to a vesicle

Released via exocytosis

Examples of amino acid neurotransmitters:

Glutamate - excitatory

Norepinephrine – excitatory

GABA - inhibitory

Glycine - inhibitory

Opioid peptides examples and functions:

Naturally occurring neuropeptides that act as endogenous agonists at opioid receptors in the central nervous system

Play a vital role in regulating pain, mood, and other physiological processes

Beta endorphin: analgesic (pain relief) effects

Enkephalin: regulate pain

Dynorphin: pain and reward

Synthesis and Removal of Acetylcholine:

Synthesis

• Acetylcholine is synthesized in the presynaptic terminal from choline.
• Acetyl CoA and Choline are converted to Acetylcholine by the enzyme Choline Acetyltransferase (ChAT).
• Choline is the rate-limiting step.

Removal

• Acetylcholine is terminated by acetylcholinesterase (AChE) in the synaptic cleft which converts acetylcholine into choline and acetate (both of which are transported back into the cell).

Two types of acetylcholine receptors and how they differ:

Nicotinic (ionotropic):

Allows the passage of sodium (Na+)

Binding causes depolarization

Muscarinic (metabotropic):

Stimulatory G-proteins

Associated with a series of intracellular signals

Acetylcholine distribution and functions:

Basal forebrain (telencephalon)

Dorsolateral tegmentum of the pons

Somatic motor neurons

Preganglionic neurons of the autonomic nervous system

Parasympathetic nervous system

Causes muscle contractions at the neuromuscular junction

Increases activity of the parasympathetic nervous system

Involved in learning and memory in the central nervous system

Associated in sleep-wakefulness

Acetylcholine inhibition:

Cholinesterase inhibitors increase activity at acetylcholine receptors by blocking the breakdown of acetylcholine

Buildup of acetylcholine and continuous activation of the cholinergic receptors

Types of Glutamate receptors:

Binds to both ionotropic (NMDA, AMPA, and Kainate) and metabotropic (mGluR1-mGluR8) receptors

NMDA, AMPA, and Kainate allow the passage of sodium (Na+)

Depolarization occurs when glutamate binds to these receptors

NMDA also allows the passage of Calcium (Ca++), which activates second messengers within the cell

Glutamate distribution and functions:

Found in 80% of neurons near the cortex

Released to excite other neurons

Is the main excitatory neurotransmitter in the central nervous system (EPSPs)

Glutamate toxicity:

Excessive levels of glutamate due to glutamate receptors being overstimulated

Enhanced activation of NMDA receptors overexcites cells

Causes cell death due to calcium ions (Ca2+)

Implicated in Alzheimer’s, Huntington’s, amyotrophic lateral sclerosis, traumatic brain injury, and stroke

GABA synthesis and removal:

Synthesis:

• GABA synthesis occurs in the presynaptic terminal, where glutamate is converted into GABA by glutamic acid decarboxylase (GAD).

Removal:

• GABA is terminated by reuptake by neurons and astrocytes, which the covert it back into glutamate via GABA aminotransferase. Then, the glutamate is covert to glutamine.

Types of GABA Receptors

• GABAA (ionotropic) – Allows Chlorida
• GABAB (metabotropic)

Distribution and Functions

• Main inhibitory NT in the CNS -High concentration in the brain & spinal cord
• Regulates neuron excitability

Relate to Various Disorders:

• Anxiety disorders
• Mood disorders
• Epilepsy
• Schizophrenia
• Autism

Histamine:

• Synthesized: Presynaptic terminal from the amino histidine via active transport.
• Peripheral Synthesized: via mast cells
• Inactivation: Metabolized by two enzymes, histamine methyltransferase and diamine oxidase -Olfactory (I): smell.

Optic (II): vision.

Oculomotor (III), Trochlear (IV), Abducens (VI): eye movement.

Trigeminal (V): chewing and facial sensation.

Facial (VII): facial expression and taste (anterior 2/3 of tongue).

Auditory (VIII): hearing and balance.

Glossopharyngeal (IX): swallowing, salivation, and taste (posterior 1/3 of tongue).

Vagus (X): heart, lungs, GI tract, larynx.

Spinal accessory (XI): neck muscles/viscera/swallowing.

Hypoglossal (XII): tongue movement.