C2006/F2402 '04 Outline for Lecture 19 -- (c) 2004 D. Mowshowitz -- Lecture updated 04/08/04
Handouts: 19A Circuits, 19B CNS/PNS, 19C PNS (Extra copies in boxes outside Dr. M's office; 7th floor Mudd.)
This lecture will fill in some features of the nervous system not covered by Dr. Firestein. Muscle will be covered next time. Parts of topics I & II have already been covered by Dr. F, but are included here for reference.
I. Patch Clamps -- how are ion flows through channels measured? -- See Becker fig. 9-8 or Purves 44.12 (41.11.)
A. What's a clamp? Have electrode in/on surface of cell -- called clamp if adjust current through electrode to keep voltage across cell surface constant.
B. What's a patch? Electrode = small glass pipette; tiny piece of membrane seals opening = patch. Patch can be left in place on cell or pipette can be removed, carrying isolated patch of membrane.
C. How used?
1. Measure ion flows. Adjust current through electrode to keep voltage across patch at tip of pipette constant -- amount of current required indicates ion flows across patch.
2. Measure effects of substances on either side of membrane. Can vary substances on either side of patch to see effect on current; can infer what ions are moving, etc.
a. On outside: Can vary substances inside pipette -- change conditions on side of membrane normally facing outside of cell.
b. On inside: Can remove the electrode plus attached patch and insert electrode with patch into a solution of desired composition = vary substances on side of membrane normally facing inside of cell.
D. Any interesting results?
1. Can detect effect of opening/closing of a single channel = detect change in current due to ions passing through a single channel.
2. Can tell which channels are present/absent in particular cell regions.
3. Can detect changes that cause disease. For example, CF (cystic fibrosis) due to abnormal Cl- channel.
The use of a patch clamp is discussed in problem 8-15, part F. At this point, look at the diagram and ask yourself, suppose you wanted to open a ligand gated channel. Where would you add the ligand if it reacts with cell surface receptors in an intact cell? Would you put the ligand in the pipette or the medium? Later, after you can answer part C, try part F.
II. Nerve-Nerve Synapses, cont. For nice overall pictures see Purves 44.16 or Becker fig. 9-21 & 9-23.
A. Post Synaptic Potential (PSP) = small change in potential due to release of transmitter at a single synapse
1. Can be inhibitory (generate an IPSP) or excitatory (generate an EPSP)
a. Inhibitory -- causes hyperpolarization or stabilizes existing negative polarization due to opening of K+ or Cl- channels. Either K+ goes out or Cl- comes in.
b. Excitatory -- causes depolarization due to opening of cation channels; Na+ in>> K+ out.
2. Any given synapse is excitatory or inhibitory
a. Pre-synaptic side: Usually only one transmitter released by any neuron. Therefore one major transmitter released -- the same one -- at all synapses made by that neuron.
b. Post-synaptic side: One type of receptor for neurotransmitter at each synapse -- Receptor determines which kind of synapse it is -- excitatory or inhibitory -- see below.
3. PSP's are graded (size is proportional to stimulus), not all or none. (Unlike action potentials.)
To review IPSP's and EPSP's try problem 8-10.
B. Summation -- See Purves fig. 44.17 (41.16) or Becker 9-26 & 9-27.
1. Inputs (IPSP's & EPSP's) to cell body/dendrites are summed -- changes spread around cell body to axon hillock (or die out)
2. No AP in cell body. No voltage gated channels in cell body so no AP generated there
3. Axon Hillock. Voltage gated channels begin at axon hillock (some texts call this the "trigger zone") so AP starts there. See Becker fig. 9-16 or Purves 44.17.
4. Inputs summed over space and/or time -- need to depolarize past threshold at axon hillock to --> AP
a. Spatial summation: Multiple EPSP's delivered at different spots can add up --> AP
b. Temporal summation: Multiple EPSP's delivered close enough together in time can add up --> AP
c. Why you need summation: A single EPSP not enough to --> AP
Try Problem 8-8, parts A to H. You should also try recitation problem 8-2. Hints to the answers to the recit. prob. can be found here.
C. Transmitters -- See Purves Table 44.1 (41.1) & Becker fig. 9-22
1. One major type of transmitter per synapse (released from pre-synaptic side)
a. In CNS, many diff. transmitters. Usually amino acids or their derivatives. Major ones are glutamate (excitatory) & GABA (inhibitory).
b. In PNS usually norepinephrine (NE) or acetyl choline (AcCh)
2. Effects of transmitter can vary. Some transmitters always excit. or inhib; other transmitters vary (depends on if have one or more types of receptor for that transmitter -- see below)
3. Getting rid of transmitters
a. Transmitter doesn't remain in cleft for long.
b. Different methods for getting rid of dif. transmitters
(1). Diffusion away from synapse
(2). Destruction by enzymes in synapse. For ex, acetyl choline esterase (AcChE) in cleft breaks up AcCh (Choline is reused). See Purves fig.44.15 (41.14)
(3). Reuptake by endocytosis -- NE, serotonin removed by reuptake
c. Many drugs affect release/fate of transmitters; for ex.
(1). Prozac prevents serotonin reuptake -- transmitter stays around longer --> more stimulation.
(2). Malathion (insecticide) & nerve gas block AcChEsterase --> continuous stimulation --> spasms
d. Presynaptic inhibition/facilitation or modulation
(1). Can have synapses ending on axons -- near axon terminals
(2). These synapses affect (modulate) release of transmitter by axon terminals -- effect presynaptic side of synapse. Can increase or decrease release of neurotransmitter by axon -- change size of response to stimulus.
(3). May be involved in learning.
D. Receptors
1. Response to particular transmitter depends on receptor as with hormones.
2. Receptors are two kinds
a. Direct or ionotropic: Receptors (for transmitters) are ligand-gated ion channels; relatively fast. For examples see Purves 44.19 or Becker 9-25. Also see many pictures in both books of neuromuscular junction.
b. Indirect or metabotropic: Receptors are coupled to G proteins, generate 2nd messengers ---> open or close ion channels or have other effects (i.e. act like hormones); relatively slow. See Purves 44.18 (41.17)
3. Agonists and antagonists used as common tools to study receptors
4. Examples -- Major types of receptors in the PNS
Basic Type of Receptor
Transmitter
Detailed Type of Receptor
Mechanism
Agonist
Antagonist
Typical effect
Cholinergic
**Acetyl Choline
Nicotinic
Direct (It's a Na+/K+ channel)
Nicotine
Curare
Contract skeletal muscle
Cholinergic
AcCh
Muscarinic
Indirect; 2nd messenger & effect varies
Toxin from Amanita muscara
Atropine
Slow heart beat
Adrenergic
Epinephrine (adrenalin) & NE; NE> E
Alpha*
Indirect; 2nd messenger & effect varies
Contract smooth muscle
Adrenergic
Epi. & NE; E> NE
Beta*
Indirect; G prot --> cAMP
Asthma drugs
Beta blocker
Relax smooth muscle (bronchodilates); increase heart beat
See Becker fig. 23-18 for diagram of action of adrenergic receptors
*Both alpha and beta have subtypes that differ in location, mechanism & effect
** This is the receptor at the neuromuscular junction. This is the AcCh receptor Becker (in Ch. 9, fig. 9-25) and many others mean when they talk about "THE" acetyl choline receptor.
Look at problem 8-16, part C. Assume you are looking at a standard synapse between two nerves that uses AcCh as a transmitter. What are the answers to parts 1-5? (Note -- this problem as written does not refer to a standard synapse between two nerves. However the answers in the back of the book are still okay except for part 4. What is the right answer to part 4 for a standard synapse?)
III. Circuits -- how nervous system is organized
A. Simple circuits -- see handout 19A or Purves 46.4 (41.19 or 43.4)
1. One synapse, 2 neurons -- monosynaptic circuit -- how sensory neuron signals an effector.
2. Circuit with multiple synapses -- how antagonistic muscles are controlled. (Signal to skeletal muscle is always +; + = signal to contract; no signal = relax.)
3. Role of brain -- adds up/down (as vs. in/out) component
4. Where is all this located? see handout or text.
B. How is NS organized overall? See handout 19 B or Becker fig. 9-1 or Purves 46.2 (43.2)
1. CNS
a. CNS = brain + spinal cord
b. Interneurons. Most neurons of CNS are interneurons (99%)
c. White matter = axons
d. Grey matter = cell bodies, interneurons, and dendrites
2. PNS -- Names of Divisons
a. Afferent vs Efferent.
(1) Afferent =carrying info into the CNS
(2) Efferent = carrying info away from the CNSb. Efferent subdivided into: Somatic vs autonomic
(1) Somatic = controls skeletal muscle
(2). Autonomic = controls everything elsec. Autonomic subdivided into: Parasympathetic (PS) vs Sympathetic (S)
Try problem 8-8, part I.
C. General Set up of wiring of efferent PNS -- see handout 19C
1. First neuron -- same in Somatic and autonomic.
a. body in CNS
b. releases AcCh (nicotinic receptor on effector/next neuron)
2. Second neuron (post ganglionic) -- found in autonomic only
a. Body in ganglion
b. Releases AcCh (muscarinic receptor on effector) or NE
c. Adrenal medulla = second neuron with a short axon
Try problem 8-8 part J.
D. PS vs S -- factors to compare and contrast (see handouts and Purves fig. 43.11)
1. Where are ganglia? Near spinal cord or target organs?
2. Where are bodies in CNS = where in spinal cord/brain stem do axons of first neuron come from? See bottom of 19B.
3. What type of synapse with effector? Cholinergic or adrenergic?
4. General effect -- stress or relaxation?
E. How do PS and S co-operate? (See Purves 43.11)
1. What do they innervate?
a. Many organs innervated by both
b. Some organs innervated (stimulated) by only one
(1). liver, sweat glands -- S only
(2). tears -- PS only
2. What results does stimulation produce?
a. Not always S excites; PS inhibits. Ex: salivation -- S inhibits; PS excites
b. Usually: S --> response needed in a crisis; PS --> response needed in relaxed state.
c. Examples:
(1). S --> heart rate up; liver releases glucose; bladder relaxes (to hold more).
(2). PS --> heart rate down, digestion, salivation up.
To review the organization of the nervous system, try Problems 8-12 to 8-14.
IV. Stress response -- How do hormones and nerves act together to respond to stress? See Lecture 15, handout 15B top. .
A. Phase one -- Sympathetic stimulates target organs (that are not glands) --> Direct response of heart, liver, lungs, etc.
B. Phase two -- Sympathetic activity --> activation of glands
1. Stimulate pancreas ---> glucagon up; insulin down --> additional stim. of some target organs
2. Stimulate adrenal medulla --> release of epinephrine --> stimulation of same and additional targets.
C. Phase three -- HT in brain --> releasing hormone for ACTH --> AP --> ACTH --> adrenal cortex --> cortisol --> target organs; get stimulation of breakdown of fats & protein (instead of glucose); inhibition of immune system.
V. Sensors
A. Receptors. Special cells contain receptors for stimuli (pressure, light, heat, chemicals, etc.).
B. Two Types of Receptor Cells. Special cell with receptors can be modified neuron capable of generating AP itself, or receptor cell that triggers AP in next cell.
C. Response is graded. Stimulus creates local graded response (receptor potential or generator potential) in receptor cell or modified neuron
D. What causes Graded response? Change in polarization of membrane due to opening or closing of channels
E. What opens/closes channels? Channels opened directly (receptors for pressure, temperature, voltage) or through 2nd messengers (chemoreceptors, photoreceptors). See Purves 45.1(42.1)
F. How Does Graded response generate an AP? -- see Purves 45.2.(42.2)
1. In modified neuron. Graded response (generator potential) triggers AP in same cell (if stimulus.over threshold) --> input to CNS. Example: smell (olfaction).
Receptor --> G protein --> adenyl cyclase --> cAMP up --> open cation channel (cyclic nucleotide gated channel) --> depolarize cell --> AP.
2. In separate receptor cell: Graded response (receptor potential) triggers release/inhibition of transmitter by receptor cell -- amount of transmitter released proportional to stimulus. Transmitter generates IPSP or EPSP in neuron (next cell = post synaptic cell). Transmitter triggers AP in neuron if stimulus is over threshold --> input to CNS. Example: vision, taste.
Which type are you dealing with in problem 8-16?
3. Details for Vision
a. Receptor cell (in the dark) releases an inhibitory transmitter, so post synaptic neuron remains hyperpolarized and does not fire.
Details FYI: Receptor cell is less polarized than usual to begin with; continually generates cGMP. This keeps cation channel open and cell partially depolarized --> release of neurotransmitter (inhibitory).
b. Binding of photons to pigment in receptor cell blocks release of inhibitory neurotransmitter. Post synaptic neuron depolarizes and fires an AP.
Details FYI: Receptor (rhodopsin w/ cis retinal) binds photon --> rhodopsin w/ all trans retinal --> G protein --> activates PDE --> cGMP degraded --> cation channel closes, cell hyperpolarizes --> less (inhibitory) transmitter release --> AP in next cell. For more details see Purves Ch. 45 (42)
G. All stimuli give same message to CNS (= AP's)
(modality) of stimulus -- taste, stretch, etc. (Take a very sharp pencil and tap your upper lip. What sensors did you trip off?)1. Number, frequency of AP's indicate length (duration) and strength (intensity) of stimulus.
2. Wiring (what part of brain is stimulated) indicates location of stimulus and type
To review sensors, try Problem 8-16 . To review electrical communication overall, try 8-15.
Next time: How do nerves and muscles work to give contractions?
