Physioweek2

Updated for 1999 PSY 314 Physiological Psychology
Brooke J. Cannon, Ph.D.
LECTURE NOTES
WEEK 2
Chapters 2, 4 CELLS OF THE NERVOUS SYSTEM
Neurons
External structures:
soma - cell body, contains nucleus and structures required for sustaining life of the cell
dendrites - message receivers
axon - carries info away from soma to terminal buttons
terminal buttons - secrete neurotransmitters

3 types:
multipolar-somatic membrane has 1 axon and many dendritic trees
bipolar - 1 axon and 1 dendritic tree, and opposite ends of the soma
unipolar - one stalk, divides

Internal structures:
membrane - like skin of cell, define boundary
nucleus - surrounded by nuclear membrane and contains:

nucleolus which makes ribosomes, small structures involved in protein synthesis
chromosomes - contain the organism’s genetic information, composed of long strands of deoxyribonucleic acid (DNA); portions of chromosomes (genes) produce messenger ribonucleic acid (mRNA), which leaves nuclear membrane and attaches to ribosomes to produce a specific protein

cytoplasm - makes up most of the cell; jellylike
mitochondria - produce adenosine triphosphate (ATP), which is the cell’s immediate source of energy
endoplasmic reticulum - primarily channels for transporting chemicals thru the cytoplasm. 2 types:

1. rough - contains ribosomes which produce protein for transport outside of the cell or for use inside (also unattached ribosomes within cell which create proteins for inside use)
2. smooth - transport, produces lipid molecules

Golgi apparatus - special type of endoplasmic reticulum. 2 functions:

1. serves as wrapping center, for transport out of the cell
2. also produces lysosomes - small sacs that contain enzymes which break down substances no longer needed by the cell

neurofilaments - long protein fibers that give the cell its shape
microtubules - transport substances around the cell

Supporting Cells
Glia - "glue CNS together", hold cells in place, insulation, housekeeping. 2 types:

1. astrocytes - surround synapses to limit neurotransmitters; phagocytosis - engulf dead cells, form scar tissue
2. oligodendrocytes - produce mylein sheath for several sections of adjacent axons, series of segments each 1mm long, gaps called nodes of Ranvier

Schwann Cells - in the PNS, 1 Schwann per myelin segment -whole cell wraps around; provide tunnel for nerve regrowth

COMMUNICATION WITHIN A NEURON
Electrical potential of axons
membrane potential - relative charge of the inside of the membrane vs. the outside
resting potential - inside of membrane is -70 millivolts (mV)
depolarization - application of positive charge to outside results in depolarization (movement away from a pole toward the center)
hyperpolarization - further negative, beyond resting point
action potential
threshold of excitation - voltage level that triggers an action potential (e.g., shock number 4 on overhead)

Membrane potential
diffusion - process by which molecules distribute themselves evenly; tend to move from high to low areas of concentration to "even out"
electrostatic pressure - force exerted by forces between ions (charged particles)

cations - positive charge
anions - negative charge

Ions in cellular fluids
intracellular and extracellular
organic anions (A-) - byproducts of cell activity, only in intracellular fluid - unable to leave cell
chloride ions (Cl-) - found mostly extracellular
sodium ions (Na+) - found mostly extracellular
potassium (K+) - found mostly intracellular
forces of diffusion - push K+ out, and Na+ and Cl- in
electrostatic pressure - keeps K+ in and Cl- out, pulls Na+ in
so, K+, Cl- stay where they are - balanced forces

sodium-potassium pump
proteins in membranes generate sodium-potassium transporters, exchanging Na+ for K+, pushing out 3 Na+ for every 2 K+ they push in
Na+ doesn’t leak thru membrane, although some K+ does (100 times more permeable), so bringing in K+ doesn’t alter the K+ concentration much

Action potential
Cell membrane contains ion channels which open/close following stimuli-threshold of excitation; they are voltage-dependent, such that the Na+ channels open first, more sensitive to depolarization, and they close at the peak of the action potential; potassium channels open later

STAGES OF ACTION POTENTIAL-FIGURE 2.15 ON EXAM

Na+ channels results in rush in of Na+; voltage inside cell changes from -70mV to about +40 mV
then K+ channels begin to open
Na+ channels close
K+ leaves cell by diffusion and electrostatic pressure, causing membrane to return to resting level
K+ channels close; extra K+ outside causes hyperpolarization; eventually diffuses away

Conduction of the action potential
All-or-none law - action potential either occurs and is transmitted down the axon, or doesn’t occur at all
cable properties - passive conduction of electrical current, gradually decreasing, down the length of an axon, similar to the way in which electrical current runs down a submarine cable
saltatory conduction - hopping from node to node; action potential starts, then is carried via cable properties through the axon covered by myelin, until it reaches a node where Na+ channels can open and the action potential can occur...

2 advantages:
economic - less pumping required, unlike unmyelinated axons
speed - cable property conduction is very fast

SYNAPTIC TRANSMISSION

Did anyone find the error on page 44? On page 105?

You do not need to know the synthesis of the different neurotransmitters, other than that L-Dopa is a precursor for dopamine, choline is a precursor for acetylcholine, and tryptophan is a precursor for serotonin

KNOW FIGURE 4.6!

First paragraph of page 95 is a very nice summary of synaptic activity…

Four types of messengers:

1) Neurotransmitters: released by terminal buttons of neurons and detected by receptors in the membrane of another cell a short distance away.
2) Neuromodulators: released in large amounts from the terminal buttons, but diffused throughout part of the brain, affecting many neurons
3) Hormones: produced by endocrine glands, released into extracellular fluid - stimulate cell receptors on membrane surface or deep within nuclei of cells, including neurons
4) Pheromones: chemicals released into the environment through sweat, urine, or secretions of special glands. Most receptors in nose of other animals, but may also be detected in skin or other organs.

Synapses
presynaptic membrane
postsynaptic membrane
synaptic cleft
synaptic vesicles - 2 types:

small

large

binding site

Transmitter Release

small synaptic vesicles attach to membrane and break open; some may already be "docked"
release zone contains voltage-dependent calcium channels which open when the action potential arrives; most calcium ions are in the extracellular fluid (so, calcium+ flows in due to both diffusion and electrostatic pressure forces)
calcium allows synaptic vesicle and presynaptic membranes to fuse, neurotransmitter is released
pinocytosis - where axon meets terminal button, small buds of membrane pinch off into the cytoplasm - move to cisterna in Golgi apparatus, where they are recycled

Receptor Activation
postsynaptic receptors
once binding occurs, neurotransmitter-dependent ion channels open in two ways:

1) Direct - neurotransmitter-dependent ion channel has its own binding site - when a molecule attaches to it, it opens - also called ionotropic receptor
2) Indirect - molecule attaches to receptor, starts a series of reactions - metabotropic receptor, require the cell to expend energy (e.g., metabolism); receptors near G protein which are activated, releasing an alpha subunit which either: 1)attaches to a special binding site of an ion channel, which then opens, producing a postsynaptic potential, or 2) attaches to and activates an enzyme in the membrane which causes production of a chemical called a second messenger, which then initiates another series of steps to open the ion channels

Postsynaptic Potentials
4 types of neurotransmitter-dependent ion channels:
1) Sodium - most important source of excitatory post-synaptic potentials - when sodium channels are opened, the result is a depolarization (less negative) - EPSP (excitatory post synaptic potential)
2) Potassium - slightly more K+ in the cell, so if channels open, K+ leaves the cell, causing a hyperpolarization (more negative) - IPSP
3) Chloride - if opened when cell is at rest, nothing happens, as forces of diffusion and electrostatic pressure are at balance; if membrane already is depolarized, the opening the channels will cause Cl- to enter the cell (which now is positive, no longer pushing Cl- out), resulting in hyperpolarization and neutralizing the EPSP
4) Calcium - like sodium, most outside cell, positive charge; when channels open, it rushes in, produces depolarization, triggers migration of vesicles, and activates enzymes which may cause biochemical or structural changes in the postsynaptic neuron

Termination of Postsynaptic Potential
1) Reuptake - extremely rapid removal of the neurotransmitter from the synaptic cleft
2) Enzymatic deactivation - for acetylcholine, postsynaptic membrane releases acetylcholinesterase, which splits ACh

Autoreceptors
they typically don’t affect ion channels, but change production/release of transmitter substance

Types of Synapses
can be axosomatic, axodendritic, axoaxonic, dendrodendritic, electrical-through a gap junction

Presynaptic Heteroreceptors
axoaxonic synapse
heteroreceptors in terminal buttons
neurotransmitter from presynaptic terminal button can facilitate or inhibit opening of calcium channels in postsynaptic terminal button

Nonsynaptic Communication
cells sensitive to neuromodulators and hormones, typically via second messenger system (metabotropic)
hormone receptors:
1) peptides - affect metabotropic receptors, second messenger goes to nucleus, where through physiological process changes occur
2) steroids - pass directly through membrane, travel to nucleus, attach to receptors and stimulate production of proteins

PSYCHOPHARMACOLOGY
Know routes of administration

Drug effectiveness
Drug response curve
Therapeutic index - ratio between dose that produces desired effect in 50% of subjects and dose that produces toxic effects in 50% of subjects

Transmitter Substances

1) acetylcholine - released at synapses on skeletal muscles - excitatory effect on skeletal muscles and inhibitory effect on heart muscle; two types of receptors:

nicotinic - ionotropic; all muscle fibers and some CNS

muscarinic - metabotropic; most of CNS

2) monoamines - don’t transmit specific info, but modulate brain function, acting as volume control, increasing/decreasing activities of particular brain regions

catecholamines - epinephrine, norepinephrine, dopamine

monoamine oxidase regulates production - also found in blood, where breaks down cheese, chocolate - otherwise would cause dangerous rise in blood pressure

indolamine - serotonin

Dopamine - can be excitatory or inhibitory, L-DOPA is precursor, decrease in dopamine related to Parkinson’s disease, increase related to schizophrenia

Norepinephrine - alertness, wakefulness; inhibitory

Serotonin - mostly inhibitory; mood, eating, sleep/arousal, dreaming; LSD interferes with serotonin, causing dreaming while awake

3) amino acids:

glutamic acid/glutamate - excitatory; lower threshold of excitation; MSG

GABA - inhibitory, raises threshold of excitation; keeps all neurons from becoming excited, as in a seizure; epilepsy may be related to abnormality in GABA-secreting neurons; GABA binding sites sensitive to benzodiazepines (valium, librium) and barbiturates and alcohol; if other 2 sites are active, they increase influence of GABA, resulting in greater neural inhibition

glycine - inhibitory, in spinal cord and lower portions of the brain; bacteria that causes tetanus (lockjaw) blocks activity of glycine synapses; removal of inhibitory effect causes muscles to contract continuously

4) peptides

endogenous opioids - 1974, discovered opium receptor, then natural ligands (enkephalins); affect analgesia, flight/hiding, reinforcement

5) lipids - natural ligand for THC, called anandamide (found in marijuana)

6) nucleosides - for example, adenosine; released by glial cells as well as neurons, when oxygen supply is low; causes nearby blood vessels to dilate; also works as a neuromodulator; adenosine receptors are coupled to G proteins and cause opening of potassium channels, resulting in inhibition; caffeine blocks adenosine receptors

7) soluble gases - carbon monoxide; nitric acid (diffuses out of cell as soon as created, affects other cells, where it activates an enzyme which produces a second messenger)

Synaptic Effects - Figure 4.6 on exam!

Agonists:
1) substance serves as precursor, resulting in increased production - L-DOPA effect on dopamine
2) drug inactivates destruction of extra neurotransmitter (e.g., monoamine oxidase) - iproniazid effect on serotonin
3) drug stimulates release of transmitter substance - black widow spider venom effect on ACh
4) drug blocks reuptake - cocaine effect on dopamine
5) drug stimulates postsynaptic receptors - nicotine, muscarine effect on ACh
6) drug inactivates acetylcholinesterase - physostigmine effect on ACh

Antagonists:
1) substance inactivates enzyme involved in synthesis of neurotransmitter - PCPA effect on serotonin
2) drug keeps neurotransmitter from being stored in vesicles - reserpine effect on monoamines
3) drug stimulates autoreceptors - apomorphine effect on dopamine
4) drug inhibits release of neurotransmitter substance - botulinum toxin effect on Ach
5) drug blocks postsynaptic receptors - curare, atropine effect on ACh