31
📖 Lesson

Chapter 31

PSYP610 - Neurological Bases of Behavior

🎯 Objectives

To familiarize students with:

  • Various neurotransmitters 🧪 and their role in behavior modulation 🧠🎭
  • Classification of neurotransmitters 📋: Monoamines 🧪 (Catecholamines 💎 and Indoleamine 🌙), Acetylcholine 🔌, Amino acids 🔤, and Peptides 🧬
  • Neurotransmitter's role in behavior modulation 🎮 and aberration 💥
  • Drugs 💊 and behavior 🧠: Classification of psychopharmacological substances 💊🔬
  • Behavioral correlates 🎭 and treatment 🏥
  • Mechanism of synaptic transmission ⚡🔗

⚡ Neurotransmitters: Synaptic Transmission

Synaptic transmission 🔗📡 can be divided into several clear-cut major steps 🪜. These are relatively independent 🔄; however, each step must occur before the next one 1️⃣➡️2️⃣➡️3️⃣.

1️⃣ Synthesis and Storage of NT in Synaptic Vesicles 🏭🎒

The synaptic vesicles 🎒 are storage containers 📦 where NT 🧪 is protected from deactivating enzymes ⚗️❌, preventing degradation 💥 in the cytoplasm 💧. These vesicles 🎒 are safe transporters 🚛 of NT 🧪.

🏭 Where do vesicles come from?

Synaptic vesicles 🎒 are manufactured 🏭 from proteins 🥩 in the cytoplasm 💧 of the cell body 🧫 by the Golgi apparatus 📦. These then travel down ⬇️ towards the axonal endings 🔌 to the synaptic buttons 🎯.

📦 Packaging Differences:

  • Peptide group 🧬 NTs: Packaging takes place in the cisternae in the synaptic buttons 🎯🏭 (button or bead-like bulbous ends 💡)
  • Non-Peptide class 🧪 NTs: Packaging into vesicles 🎒 occurs within the cytoplasm 💧 before transport ⬇️ to axonal synaptic buttons 🔌🎯

🚛 Axonal Transport Systems:

Material can be transported in two different directions 🔄:

📤 Anterograde (Forward) Transport:

  • Fast anterograde transport 🏎️💨: Fast-track mechanism 🛤️⚡ moving materials from cell body 🧫 through microtubules 🧵 towards synaptic ending 🎯
  • Synaptic vesicles 🎒 travel at very fast speed ⚡ of 400 millimeters per day 📏💨
  • Like driving in the fast lane 🏎️🛣️
  • Slow anterograde transport 🐌: Materials and vesicles 🎒 ooze along 🐌 the axon 🔌 in cytoplasm 💧 at very slow speed 🐢 of less than 10 millimeters per day 📏🐌

2️⃣ Release of Neurotransmitter 📤⚡

When the action potential ⚡ reaches the presynaptic ending 🔌🎯, it is translated into a chemical message 🧪📨 (neurons can communicate in both systems 💻🧪!).

⚡ Process of NT Release:

  1. Action potential arrival ⚡📥: Arrives at terminal button 🔌🎯
  2. Calcium channels open 🚪➕➕: Calcium gates open 🔓, allowing Ca²⁺ ➕➕ to enter the button 📥
  3. Triggers NT release 🎯📤: Calcium influx ➕➕ triggers release of neurotransmitter 🧪

🔬 Key Finding: If calcium is reduced ⬇️ in extracellular space 🌍, NT amount released is reduced ⬇️. If extracellular calcium is increased ⬆️, NT amount released is increased ⬆️ 📊.

📤 Exocytosis Process:

  1. a) NT vesicles 🎒 move towards terminal 🔌➡️🎯 to empty contents 📤 into synaptic cleft 🌊
  2. b) NT vesicles 🎒 fuse with 🔗 presynaptic membrane 🧫; membrane opens up 🔓 and NT molecules 🧪 are released into cleft 🌊
  3. c) Vesicle merges 🔗 as part of presynaptic membrane 🧫; rupture or break 💥 eventually mends 🩹

3️⃣ Generation of Post Synaptic Potential 📥⚡

Action at the receiving end 📥 at the post synaptic potential after NT molecule 🧪 is received. When NT molecule 🧪 crosses the synaptic cleft 🌊 (like crossing a river full of alligators 🐊!), it gets transferred to postsynaptic membrane 🧫 for action ⚡.

🎯 Processes at Post Receptor Sites:

a) Binding of NT Molecules to Post Receptor Site 🔗🎯:

All molecules 🧪 released rush to reach 💨 and enter 📥 post receptor sites 🎯. Entry requires they must connect or "bind" 🔗 chemically with membrane site 🧫 (a receptor protein 🥩🎯). The membrane is very specialized 🎯 with particular configuration 🔷; only those resembling that shape 🔷 and chemical composition 🧪 can bind 🔗 these sites. Gates 🚪 open only to specific molecules 🔐!

b) Changes in Ionic Gates 🚪⚡:

NT molecule 🧪 leads to changes in chemically gated ionic channels 🚪⚡ in receptor membrane 🧫 for further action ⚡ through:

  • i) Direct Method ➡️: Binding of NT 🧪 to receptor 🎯 can directly open 🔓 or close 🔒 chemically gated channels 🚪 in surrounding membrane 🧫 (makes it more permeable 🌊)
  • ii) Indirect Method 🔄: Series of chemical changes 🔄 in molecules in cytoplasm 💧 bring about change in status of chemically gated ion channels 🚪⚡ of post receptor site 🎯. These changes involve chemicals/molecules 🧪 (2nd messenger 📨2️⃣, Cyclic Adenosine Monophosphate 🔄🧪) involved in conversion of Adenosine triphosphate to cAMP ⚡ through enzymes ⚗️

Note: Cyclic AMP 🔄⚡ is needed for energy 🔋 in the cell 🧫 for action ⚡. The second method uses class of molecules called 2nd messenger 📨2️⃣ (intermediates that translate messages 📡🔄). Effect of cAMP is brief ⏱️...

4️⃣ Action in Post Receptor Membrane 🧫⚡

In postsynaptic membrane 🧫, two kinds of actions can take place:

  • EPSP (Excitatory Post Synaptic Potential) ✅⬆️: Generates action potential ⚡ in postsynaptic membrane 🧫
  • IPSP (Inhibitory Post Synaptic Potential) 🚫⬇️: Inhibits ongoing activity ⚡ in cell membrane 🧫

Both actions depend on:

  1. a) Type of NT involved 🧪: Some NT's are excitatory ✅ (e.g., Glutamate 🧪⬆️), some inhibitory 🚫 (e.g., GABA 🧪⬇️)
  2. b) Site of action 📍: NT action may be excitatory ✅ at some sites 📍 and inhibitory 🚫 at other sites 📍

5️⃣ Inactivation of NT 🚫🧹

What happens to NT 🧪 after release from vesicles 🎒?

❌ NT cannot:

  • Stay in the neuron 🧠 or cleft 🌊
  • Keep activating postsynaptic membrane 🧫⚡ (otherwise one dose of amphetamine 💊 could last a lifetime ⏰!))
  • Continue in cleft 🌊 cluttering sites 🎯 (would fill up!)

✅ NT must be removed 🚫 or degraded 💥 for efficient, clean systems 🧹✨!

🔄 Two Processes of NT Deactivation:

1️⃣ Reuptake 🔄📥:

  • NT can return 🔙 to presynaptic areas 🔌 for recycling ♻️ and reuse 🔄
  • Reuptake processes allow presynaptic area 🔌 to reabsorb 🔄 molecules 🧪
  • These are repackaged 📦 into vesicles 🎒 and used again ♻️

2️⃣ Deactivating ⚗️💥:

  • Active chemical state 🧪⚡ of NT is deactivated by specialized enzymes ⚗️🔬
  • Enzymes locate free-floating 🌊 unprotected NT molecules 🧪❌ in synaptic cleft 🌊 (and presynaptic areas 🔌)
  • Degrade them 💥 for excretion ➡️🚮 out of cleft 🌊
  • Like little Pac-men 👾 running after molecules 🧪!

6️⃣ Recycling of Vesicular Membrane ♻️🎒

Vesicles 🎒 that ruptured 💥 are recycled ♻️. When many synaptic vesicles 🎒 release molecules 🧪 after fusing 🔗 with presynaptic membrane 🧫 through exocytosis 📤, the terminal button 🎯 gets swollen 💢 with leftover vesicles 🎒. Pieces of excess 🎒 are broken off 💥 and returned to cytoplasm 💧🔙.

♻️ Four Ways Vesicles Can Be Reused:

  1. a) Filled with non-peptide NT 🧪 by cisternae 🏭
  2. b) Sent back 🔙 to cell body 🧫 by retrograde transport 📥 (traveling at 200 millimeters per day 📏⚡)
  3. c) Refilled with NT 🧪 by Golgi bodies 📦 in cell soma 🧫
  4. d) Broken down 💥 and molecules recycled ♻️

🔬 Methods of Locating NT

Apart from neuroanatomical tracing techniques 🗺️🔬, following techniques are especially used for NT localization 📍:

1️⃣ Histofluorescence Technique 💡🔬

  • Developed by Falck and Hillarp 👨‍🔬👨‍🔬 around early 1960's
  • Monoamine group 🧪 of NT's when exposed to formalin fixative 🧪 glow 💡✨ under fluorescent light 💡
  • Useful in locating 📍 various monoamines 🧪, their sites 🎯, their systems 🌐
  • ⚠️ Limitation: Non-specialized ❌; doesn't differentiate between various NT 🧪 within monoamine class

2️⃣ Receptor Binding Autoradiography ☢️📸

  • NT are radiolabeled ☢️🏷️ with radioactive isotope (Hydrogen-3 or Carbon-3)
  • Neural tissue 🧠 exposed to labeled ligand 🧪🏷️ (molecule that binds 🔗 to target 🎯)
  • Can inject directly ➡️ into brain 🧠 and expose slices 📏 for longer period after decapitation 💀✂️
  • Slices 📏 exposed to photographic plate 📸 which reacts to radioactivity ☢️
  • High radioactive areas show up ✨ in plates 📸

3️⃣ Monoclonal Antibodies 🧬💉

  • Involves immunocytochemistry procedures 🔬🧪
  • Lymphocytes secrete antibodies 🛡️; hybrid lymphocytes and bone marrow cells secrete antibodies 🛡️ and subdivide 🔄
  • Same process used to identify antibodies 🛡️ for particular proteins 🥩 (all NTs are chains of amino acids 🧬)
  • Specific monoclonal antibodies 🛡️🎯 developed and injected identify specific regions 📍 and target proteins 🥩🎯

4️⃣ Microiontophoresis (Push-Pull Cannulae) 🔬📊

  • Analyzes chemicals 🧪 being released within synapse 🔗
  • Response of postsynaptic sites 🎯 monitored using double-barreled pipette 🔬
  • Tip of inner pipette (contains saline 💧) inserted into postsynaptic membrane 🧫 to record intracellular voltage ⚡
  • Weak current ⚡ passed to stimulate neuronal ending 🔌 leads to discharge 💥
  • Pulled out for analysis 🔬, checked at oscilloscope 📊 for EPSP's ✅ or IPSP's 🚫

🧪 Major Neurotransmitters

There are a large number of neurochemicals 🧪 classified as neurotransmitters 📡. There are six (6) major groups 📋, each with several independent neurotransmitters 🧪 with specific actions ⚡.

1️⃣ Amino Acids 🔤

  • Formed from chains of amino acids 🧬 (basis of proteins 🥩)
  • Major NTs: Glutamate 🧪⚡, GABA (Gamma aminobutyric acid) 🧪🚫, Glycine 🧪, Aspartate 🧪
  • Largest group 📊 with relatively quick-acting ⚡ synaptic connections 🔗
  • Glutamate ✅: Excitatory neurotransmitter ⚡⬆️
  • GABA 🚫: Inhibitory neurotransmitter ⚡⬇️

2️⃣ Monoamines I: Catecholamines 💎

  • Synthesized from single amino acid 🧬 (mono = single 1️⃣, amine 🧪)
  • Modulate wide range of behaviors 🎭🌐
  • Neurons have little bulbous bead-like knobs 📿 throughout axon length 🔌
  • NT seeps out 💧 through these knobs 📿
  • Called catecholamines 💎 because they have one catechol group 🧪
  • The catecholamines:
    • Dopamine (DA) 🧪😊: Movement 💪, reward 🏆, motivation 💪
    • Norepinephrine (Noradrenaline) 🧪⚡: Alertness 😊, arousal ⚡
    • Epinephrine (Adrenaline) 🧪💥: Fight-or-flight 💪🏃

3️⃣ Monoamines: Indoleamine 🌙

  • Belongs to monoamine group 🧪 but different structure 🔷
  • Has indoleacetic acid 🧪 attached to amine group 🧬
  • Serotonin (5-HT) 🧪😌: Mood 😊😢, sleep 😴, appetite 🍽️, pain 😣

4️⃣ Soluble Gases 💨

  • Small molecule NT 🧪🤏
  • Follow different transmission mechanism 🔄
  • Lipid-soluble 🧈, diffuse through 🌊 cell membrane 🧫 into extracellular space 🌍 to pass into other cells 🧫
  • Work through 2nd messengers 📨2️⃣
  • Break down immediately ⚡ after action
  • Examples: Nitric oxide (NO) 💨, Carbon monoxide (CO) 💨

5️⃣ Acetylcholine (ACh) 🔌

  • Small molecule transmitter 🧪🤏
  • One of its kind 1️⃣—no other NT's in this group
  • Only NT 🧪 that works on neuromuscular junctions 💪🔗
  • Muscle contraction 💪, memory 📚, learning 📚🔬

6️⃣ Neuropeptides 🧬

  • Large number of peptides 🧬 (chain of 5+ molecules) floating in brain 🧠
  • Possible candidates for NT status 🧪❓
  • Well-known peptides:
    • Brain opioids 🧪😌: Endorphins 🧬 (large molecules), Enkephalins 🧬 (small molecules)
    • Pituitary peptides 🏭🧬
    • Substance P 🧪😣: Pain transmission 😣📡
    • And many others 🧬...

📚 References

  • Kalat, J.W. (1998). Biological Psychology. Brooks/Cole Publishing Company.
  • Carlson, N. R. (2005). Foundations of physiological psychology. Pearson Education New Zealand.
  • Pinel, J. P. (2003). Biopsychology. (5th ed). Allyn & Bacon Singapore.
  • Bloom, F., Nelson., & Lazerson. (2001), Behavioral Neuroscience: Brain, Mind and Behaviors. (3rd ed). Worth Publishers New York
  • Bridgeman, B. (1988). The Biology of Behavior and Mind. John Wiley & Sons, New York
  • Brown, T.S. & Wallace, P.S. (1980). Physiological Psychology. Academic Press, New York
  • Seigel, G. J., Agranoff, B.W, Albers W.R. & Molinoff, P.B. (1989). Basic Neurochemistry: Molecular, Cellular and Medical Aspects
  • Cooper, J.R., F.E Bloom, F. E., & Roth, R. H. (1970). The Biochemical basis of neuropharmacology (5th Ed.). New York, Oxford Univ. Press.