C2006/F2402 '06 Outline for Lecture 19 --  (c) 2006 D. Mowshowitz  -- Lecture updated 04/03/06.

Handouts: 19B (bottom) Circuits  19B (top) CNS/PNS , 19A PNS  On line handouts have some features not on class handouts & are lacking diagram of summation. Extra copies of class handouts are 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.

Note on refractory periods: There is some disagreement between authorities on the timing of the refractory periods. According to some,  the absolute refractory period coincides more or less with the spike; the relative refractory period follows after the spike. All agree about the underlying mechanism. The absolute refractory period corresponds to the time when the Na⁺ channels are inactivated (so depolarization is not possible). The relative refractory period corresponds to the time when the Na⁺ channels can be activated, but the voltage gated K⁺ channels are still open (so depolarization to threshold requires a larger stimulus).

I. Nerve-Nerve Synapses, cont. For nice overall pictures see Purves 44.13 (44.16) or Becker fig. 13-19  & 13-21 (9-21 & 9-23). Some of this is review, but is included for clarity. What determines if a nerve impulse will be passed on to the next neuron?

    A. Presynaptic Side -- Transmitters  -- See Purves Table 44.1 & Becker fig. 13-20 (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. One transmitter per Neuron. Usually only one major transmitter released by any neuron. Therefore one major transmitter released -- the same one -- at all synapses made by that neuron.

3. Effects of transmitter can vary. Some transmitters always excit. or inhib; other transmitters vary (depends on if have one or more type of receptor for that transmitter -- see below.)

4. Getting rid of transmitters

a. Transmitter doesn't remain in synaptic cleft for long.

b. Different methods for getting rid of dif. transmitters

(1). Diffusion away from cleft

(2). Destruction by enzymes in cleft. For ex, acetyl choline esterase (AcChE) in cleft breaks up AcCh (Choline is reused). See Purves fig.44.14 (44.15)

(3). Reuptake by transporters (secondary active transport) -- NE, serotonin removed from cleft by reuptake. (Endocytosis recovers membrane; transporters recover transmitters.)

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

    B. Post Synaptic Side --PSP's = post synaptic potentials = 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 -- What determines it?

a. Receptor is crucial

(1). One type of receptor for neurotransmitter at each synapse.

(2). Receptor determines which kind of synapse it is -- excitatory or inhibitory. 

(3). Same neurotransmitter can be excitatory or inhibitor at different synapses.

b. Overall: One receptor/neurotransmitter pair per synapse. (Receptors of PNS are in table below.)

3. Features of PSP's (To compare to AP's)

a. PSP's are graded  -- size is proportional to stimulus (as with receptor potentials, see below). Size is not all or none. (Unlike action potentials.)

b. PSP's are local -- die out if don't reach threshold. (Not regenerated like AP's.)

c. PSP's are caused by opening/closing of ligand gated channels. (What kind of channel is needed for AP's?)

To review IPSP's and EPSP's try problem 8-10.

    C. Post Synaptic Side -- Summation  -- See Purves fig. 44.15 (44.17) or Becker 13-24 (9-26 & 9-27).

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:

    (1). A single EPSP is not enough to → AP

    (2). IPSP's & EPSP's are summed: net effect depends on both inhibitory and excitatory input. Remember there are about 1000 synapses (inputs) on body & dendrites of average neuron. See Becker fig. 13-24 (9-27). (See circuits below for how you use this.)

Review Problem 8-8, parts A to H, and recitation problem 11-1. 

II. Sensors Purves has a whole chapter on Sensory Systems. (Chapter # depends on which edition of the text you have.) Only a few general principles discussed here. See Purves for examples & details.

    A. Receptor Cells. Two types of Sensory Cells (aka receptor cells) = special cells with molecular receptors for detecting stimuli

Question to ask yourself: What type of channels does a cell need in order to generate an AP?

    B. Receptor Proteins.

    C.  Receptor Potentials

    D. How Does Graded response generate an AP?  -- see Purves 45.2.(6th ed. only) for the two methods.

1. In modified neuron. Graded potential (generator potential*) triggers AP in same cell (if stimulus is over threshold) → input to CNS.

a. Example #1 -- direct (ionotropic receptor) -- stretch.  Purves 45.2 (7th ed.) for example.
       
    Stimulus  = stretch on nerve endings →  open channels →  depolarize to threshhold →  AP.   

b. Example #2  -- indirect (metabotropic receptor) -- smell (olfaction).

    Stimulus = Ligand (odorant) → Receptor → G protein → adenyl cyclase → cAMP up → open cation channel (cyclic nucleotide gated channel) → depolarize cell → AP. 

Question: Where will the action potential start? In what part of the cell? See Purves 45.2 (45.3)

* In older editions of Purves, the terms "generator potential" and "receptor potential" are used to refer to these two different cases respectively. Most texts stick to "receptor potential" or use the two terms interchangeably.

Which type of receptor cell are you dealing with in problem 8-16?

    E. All stimuli (whatever the modality) give same message to CNS (= AP's). If AP is all or nothing, how do you know which stimulus it was? And how much?

1. Number, frequency of AP's indicate length (duration) and strength (intensity) of stimulus.

2. Wiring (what part of brain is stimulated) = labeled lines = indicates location of stimulus and type (modality) of stimulus  -- taste, stretch, etc. If you get a punch in the eye, you set off light receptors. For a less violent example, take a very sharp pencil and tap your upper lip. What sensors did you trip off?

To review sensors, try Problem 8-16 . To review electrical communication overall, try 8-15.

III. Circuits -- how nervous system is organized

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. FYI: Where is all this located? see Purves 46.3 (46.4); will not be discussed in class.

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 CNS

b. Efferent subdivided into: Somatic vs autonomic

(1) Somatic = controls skeletal muscle
(2). Autonomic = controls everything else

c. Autonomic subdivided into: Parasympathetic (PS) vs Sympathetic (S)

1. First neuron -- same in Somatic and Autonomic.

a. Location -- body in CNS

b. Neurotransmitter -- releases AcCh

c. Receptor -- AcCh receptor (on effector/next neuron) is nicotinic

2. Second neuron (post ganglionic) -- found in autonomic only

a. Location -- Body in ganglion

b. Neurotransmitter

(1). Parasympathetic -- releases AcCh

(2). Sympathetic -- usually releases NE

c. Receptor (on effector)

(1). AcCh (cholinergic) receptor is muscarinic;

(2). NE (adrenergic) receptor can be alpha or beta (see table below)

d. Adrenal medulla -- second neuron has a short axon -- contained in medulla. Releases neurotransmitter into blood (instead of into synapse with effector).

Try problem 8-8 part J.

1. Response to particular transmitter depends on receptor as with hormones.

2. Receptors can be direct or indirect (as with hormones or sensory receptors)

a. Direct or ionotropic: Receptors (for transmitters) are ligand-gated ion channels; relatively fast. For examples see Purves 44.17 (44.19) or Becker 13-23 (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 44.16 (44.18)

3. Agonists and antagonists used as common tools to study receptors, as with hormones. Some receptors named by their most common agonist or antagonist -- see table below.

4. Examples -- Major types of receptors in the PNS

*Both alpha and beta have subtypes that differ in location, mechanism & effect; same receptors used for epinephrine acting as a hormone or neurotransmitter. (See also table at end of lecture 12.)

** This is the receptor at the neuromuscular junction. See Becker fig. 13-23 (9-25). This is the AcCh receptor people 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? What effects will you expect on transmission at a standard synapse? (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?)

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? (FYI only -- see Purves 46.10.)

3. What type of synapse with effector? Cholinergic or adrenergic?

4. General effect -- stress or relaxation?

To review the organization of the nervous system, try Problems 8-12 to 8-14.