📚 Exam Summary: Basic Neurochemistry

🧪 1. Types of Neurochemicals

Definition:
Chemicals found in brain → Made in brain OR transported via blood → Essential for neural communication

Four Categories:

Type	Function
🎛️ Neuromodulators	Fine-tune ongoing neural activity
⚙️ Neuroregulators	Act as 2nd messengers, support transmission
💉 Neurohormones	Secreted by hypothalamus/pituitary, affect behavior
💬 Neurotransmitters	Directly transmit messages between neurons

🔗 2. The Synapse - Where Magic Happens

Definition:
Junction between two neurons → Where one talks to another → Very SMALL space (few Angstroms)

Three Parts:

📤 Presynaptic Ending: Releases NT (has vesicles + mitochondria)
〰️ Synaptic Cleft: Gap between neurons (has cleaning enzymes)
📥 Postsynaptic Membrane: Receives NT (has receptor sites)

Types of Synapses:

Axo-dendritic: Axon → Dendrite (most common)
Axo-somatic: Axon → Cell body
Axo-axonic: Axon → Axon

⚡ 3. Six Steps of Synaptic Transmission

1

Synthesis & Storage: NT made in cell body → Stored in vesicles → Protected from enzymes

2

Release: Action potential arrives → Ca²⁺ enters → Triggers exocytosis → NT spills into cleft

3

Binding: NT crosses cleft → Binds to receptor (lock & key) → Only matching shapes fit!

4

Postsynaptic Response: Ion channels open → EPSP (excitatory) OR IPSP (inhibitory)

5

Inactivation: Reuptake (NT recycled) OR Degradation (enzymes break it down)

6

Recycling: Vesicle membrane recycled → Refilled with NT → Ready for next signal

Calcium is the TRIGGER for NT release! More Ca²⁺ = More NT released

✅ 4. Criteria for a Neurotransmitter

To be called a "true" NT, must meet ALL criteria:

1️⃣ Localization: Found in presynaptic ending
2️⃣ Storage: Stored in vesicles
3️⃣ Synthesis: Made by the neuron itself
4️⃣ Release: Released when stimulated
5️⃣ Receptors: Specific receptors exist for it
6️⃣ Inactivation: Mechanisms exist to remove it
7️⃣ Effect: Causes measurable postsynaptic changes

Putative NTs: Suspected NTs that haven't met ALL criteria yet (~50 waiting!)

📋 5. Classification of Neurotransmitters

Category	Examples	Key Facts
Monoamines	Catecholamines + Indoleamines
→ Catecholamines	Dopamine, Norepinephrine, Epinephrine	Made from Tyrosine amino acid
→ Indoleamines	Serotonin (5-HT)	Made from Tryptophan
Acetylcholine	ACh	First NT discovered! Neuromuscular junction
Amino Acids	GABA, Glutamate, Glycine	GABA = inhibitory, Glutamate = excitatory
Peptides	Endorphins, Substance P	Pain, mood regulation

🧬 6. Major Neurotransmitters - Details

💜 Dopamine (DA)

Pathways: Substantia Nigra → Striatum | VTA → Limbic & Cortex
Functions: Movement, reward, pleasure, motivation
Too Little: Parkinson's (tremor, rigid) | Too Much: Schizophrenia symptoms

💙 Norepinephrine (NE)

Location: Locus Coeruleus (brainstem)
Functions: Alertness, attention, fight-or-flight, mood
Low NE: Depression | High NE: Anxiety, mania

💚 Serotonin (5-HT)

Location: Raphe Nuclei (brainstem)
Functions: Mood, sleep, appetite, pain
Low 5-HT: Depression, anxiety, aggression

🧡 Acetylcholine (ACh)

Location: Basal Forebrain, neuromuscular junctions
Functions: Memory, learning, muscle control
Loss: Alzheimer's disease, muscle weakness

🔴 GABA (Gamma-Aminobutyric Acid)

Type: Main INHIBITORY NT in brain
Function: Calms neural activity, reduces anxiety
Low GABA: Anxiety, seizures | Benzodiazepines enhance GABA

🟢 Glutamate

Type: Main EXCITATORY NT in brain
Function: Learning, memory, synaptic plasticity
Too Much: Excitotoxicity (cell death) → seen in stroke

🔬 7. Catecholamine Synthesis Pathway

Tyrosine → (TH enzyme) → L-DOPA → (AADC) → Dopamine → (DBH) → Norepinephrine → (PNMT) → Epinephrine

TH (Tyrosine Hydroxylase) is the RATE-LIMITING step - controls how much NT is made!

💊 8. How Drugs Affect NT Systems

Drug Action	Effect on NT	Example
Agonist	Mimics/enhances NT	Nicotine (ACh agonist)
Antagonist	Blocks NT action	Antipsychotics (DA antagonist)
Reuptake Inhibitor	Keeps NT in cleft longer	SSRIs for serotonin
Enzyme Inhibitor	Prevents NT breakdown	MAOIs (block MAO enzyme)
Precursor	Provides building blocks	L-DOPA for Parkinson's

🧹 9. Inactivating Enzymes

AChE (Acetylcholinesterase):
Breaks down Acetylcholine → Very fast acting! → Found in synaptic cleft

MAO (Monoamine Oxidase):
Breaks down monoamines (DA, NE, 5-HT) → Found INSIDE neuron → MAOIs used for depression

COMT (Catechol-O-Methyltransferase):
Breaks down catecholamines → Found OUTSIDE neuron (extracellular)

🎯 10. Receptor Types

Two Main Categories:

Ionotropic (Fast):
NT binds → Ion channel opens DIRECTLY → Immediate effect (milliseconds)
Example: GABA-A, Nicotinic ACh receptors

Metabotropic (Slow):
NT binds → Activates G-protein → 2nd messenger cascade → Slower but longer lasting
Example: Dopamine receptors (D1-D5), Muscarinic ACh

Key Receptor Families:

Dopamine: D1, D2, D3, D4, D5 (D2 blocked by antipsychotics)
Serotonin: 5-HT1 to 5-HT7 (many subtypes!)
ACh: Nicotinic (ionotropic) + Muscarinic (metabotropic)
GABA: GABA-A (fast) + GABA-B (slow)

⚠️ 11. Disorders & NT Imbalances

Disorder	NT Involved	Treatment
Parkinson's Disease	Low Dopamine	L-DOPA, DA agonists
Schizophrenia	Excess Dopamine	DA antagonists (antipsychotics)
Depression	Low Serotonin/NE	SSRIs, SNRIs, MAOIs
Anxiety	Low GABA	Benzodiazepines
Alzheimer's	Low Acetylcholine	AChE inhibitors
Myasthenia Gravis	ACh receptor problem	AChE inhibitors

📅 12. Historical Breakthroughs

1950s: Discovery of monoamines in brain
1950s: Chlorpromazine (first antipsychotic) - revolutionized schizophrenia treatment
1950s: Reserpine found to deplete monoamines
1950s-60s: L-DOPA helps Parkinson's patients (Watch "Awakenings" movie!)
1960s: LSD, Mescaline research - serotonin connection
1970s+: Development of SSRIs for depression

⚡ QUICK EXAM CHECKLIST

✅ 4 types of neurochemicals
✅ 3 parts of synapse
✅ 6 steps of transmission
✅ Criteria for NT status
✅ Catecholamine synthesis pathway
✅ Major NTs and their functions
✅ GABA = inhibitory, Glutamate = excitatory
✅ Inactivating enzymes (AChE, MAO, COMT)
✅ Ionotropic vs Metabotropic receptors
✅ Disorders and their NT imbalances
✅ Drug actions (agonist, antagonist, etc.)

🧪 Basic Neurochemistry