1. Neuroscience and Behavior
1. Physiological basis of mind? Modern dualism?
2. Neural bases of behavior? The key philosophical theme of modern neural science is that all behavior is a reflection of brain function
3. Kandel, Schwartz, and Jessell (Principles of Neural Science), describe 5 sciences as important to the neurosciences: Anatomy, Physiology, Biochemical Pharmacology, Embryology, and Behavior.
4. Brain/behavior looks at interaction. As with all correlations, causation might be tried in different directions.
5. None is most important but all are important, including research and application
6. Nothing in the nervous system makes sense except in light of behavior!
2. Multidisciplinary experimental and explanatory approaches to behavior: Why do birds sing?
1. "Why?" is always a hard question to answer. Perhaps rephrase?
2. First--make the observation more precise.
3. Then, redefine question--under what conditions do they sing?
4. Physiological account--the mechanics of it.
5. Ontogenic (how it develops or comes to be)
6. Functional
7. Evolutionary. Probably has evolutionary function, but can be inferred.
8. Environmental/learning. plasticity within a lifetime..
3. Dualism
1. Rene Decartes (1591-1650)
2. Was invented dualism to keep free will alive?
3. This form of dualism not taken seriously now. But there are modern forms not too different.
4. Monism.
1. Physical. All is material.
2. All is mental?
5. Reductionism
1. C. Lloyd Morgan: "In no case is an animal activity to be interpreted as the outcome of the exercise of a higher psychical facility if it can be fairly interpreted ass the outcome of one that stands lower on the psychological scale."
2. Homogeneous. Deduction from a general theory of implications in which there is a commonality of terms.
3. Heterogeneous. Any explanation of a fact that takes place somewhere else, at some other level of observation, described in different terms, and measured, if at all, in different dimensions.
4. Avoid psuedo reduction: hypothetical devices for which there is no evidence.
6. Consciousness. The "split-brain" studies.
1. Symmetry (left/right).
2. Slight asymmetry in function.
3. Right brain: left half of body (except olfaction). Mostly mute in right-handed people
4. Left brain: right half of body (except olfaction). This half talks.
5. Split brain operation for treating severe epilepsy (Sperry, 1966, Gazzaniga, 1970).
6. Sever corpus callosum.
7. Patient can talk about what it's right half (left brain) experiences, but not the other half.
8. Consciousness lies in actions, what we think of as consciousness lies in language.
7. This course is about brain behavior relationships.
1. Behavior.
2. Physiology (anatomy biochemistry)
3. Neither is cause--equal partners.
8. Experimental Physiology.
1. Last two hundred years. Successful. Different from classical biology (e.g., Darwin) which described, botinized, and looked at correlations.
2. Experimental means manipulate. Change one thing and look to see what happens. A theory must direct action.

1. Consequences of Not Using Animals
1. Malaria. India. 1951. 75 million cases (800,000 deaths)
2. 1961. 50,000 cases (533 deaths, if proportions are same).
3. Due to eradication of mosquito with DDT (a separate story).
4. How was it known that the mosquito was the culprit? Ultimately, give malaria to a human.

1. One western culture has banned animal studies.
2. Recent uses of humans in ethically questionable manner.
1. Tuskeegee syphilis study, Into the 60's. Let syphilis run its course in black men. Supported by the PHS.
2. Madrazo and Mexico studies of patients with P.D. Surgical intervention. Implants of adrenal glands. Successful temporally, Monkey studies designed from what he discovered.
3. Early Parkinson's Disease work. Give MPTP to patients with PD.
4. U.S. Radiation research.

1. How Animals are Used.
1. Animal Welfare Act
2. PHS
3. IACUC
4. Pain and distress
5. Number of animals
6. Three R's: Reduce, refine, replace.

Cells.

1. Analog to circulatory system?
1. Galen and Harvey
2. The neuromuscular junction was first identified in 1860's under light microscopy. Not thought to apply to neural cells, though.
3. Cajal noted discontinuities in cerebellar cells.
4. Camillio Golgi (staining) and Santiago Ramón Y Cajál (1852-1934, anatomy)
5. Ramón Y Cajál developed neural doctrine: the principle that the nervous system is made up of many individual, communicating neurons. Suggested that flow was from axon to dentrite.
6. Sherrington (1897) coined "synapse"
2. All cells (neural or otherwise) have;
1. Membrane.
2. Nucleus (red-blood cells do not).
3. Mitochondria (maternal lineage).
4. Microtubule and filaments.
5. Ribosomes. sites where cell synthesize new protein. contains raw material and "docking site" for RNA. some free floating, others in endoplasmic reticulum.
6. Lysosomes, contain enzymes that break down many chemicals into component parts.
7. Golgi complex--network of vesicles preparing hormones for secretion.
3. Structure of neuron.
1. Cell body or soma. Contains stuff described above.
2. Dendrites and axons.
3. Myelin.
4. Terminal (presynaptic)
5. synapse.
6. New neuron or motor.
7. Processes (fibers) coming off of them. (table on board)
8. Dendrites(input to cell)
9. Axons (output)
10. Unidirectional information flow.
4. Types:
1. unipolar: One primary process, many branches. some branches may be dendrites, others axons.
2. Bipolar. Soma, one process at each end. One is dendrite. Other is axon. Axon always heads toward NS. Bipolar cells in eye, e.g.
3. Multipolar. Predominate in vertebrate. One or more dendritic process, only one axon. . A spinal motor cell, receives about 10,000 contacts (and this is moderate), a Purkinje cell in cerebellum receives a/b 150,000 contacts.

Simple organization of NS.

1. Draw simple NS, sensory afferent to motor efferent.
1. o-----< o------< o----<
2. Demonstration of speed (undergrad).
2. Sensory -< motor (unidirectional flow, afferent->efferent). No exchange of fluids.
3. Sensory1 -< interneuron-< motor

|

sensory2 -< interneuron -< motor

1. Where we are going:
1. A neuron is either at rest or discharging an "action potential," which is a brief electrical discharge. This discharge causes the release of neurotransmitter at a structure called the synapse, located at the neuron's terminal. The neurotransmitter causes the post-synaptic" neuron to be either more likely to fire an action potential, or less-likely to do so.
2. And that is the neural basis of everything that we do.
2. Afferent/efferent relative to position.
3. Glia cells. ('glue') nonneural, still active. important.
1. Myelin-providing
2. Waste-removing.
3. Guidance.
4. Blood-brain barrier.
1. Lining of endothelial (basically, lining of organs) cells that line capillaries. Out of brain, widely spaced.
2. In brain, closely spaced together, form tight junctions. Large molecules cannot pass but certain gasses can.
3. Lipids pass readily (heroin, nicotine, some gasses). Water soluble compounds do not.
4. Active transport for essential amino acids, nutrients, water-soluble glucose.

The Resting Potential

1. Voltage, Current, and Potential.
1. Voltage (V) is electrical potential: separation of charge. (Analog to water pressure)
2. Current (I) is flow of charge. (Analog to water flow).
3. Resistance (R) is constant of proportionality: V = R I
4. Conductance (G) is 1/R, also a constant of proportionality: I = VG.
5. Example: Attach a hose to a water tower.
2. Turn on a hose. Water is driven by pressure. A constant amount of water/unit time is delivered. Place a small restriction in the hose--same amount/unit time goes through the hose.
1. Metaphor for Ohm's law: (ignore formulas for undergrad).
2. Water tower provide pressure (potential). Water flows through an opening (current). Size of opening (resistance/conductance) and pressure influence current of water providing current. A pump that moves water to the tower is the energy input.
3. Consider a closed hydraulic circuit. Pump, and constriction. Pump adjusted to maintain a constant pressure. The flow rate must depend upon the width of the pipe. If there is a constriction in the pipe (an increase in resistance) then flow rate must decrease. I=E/R = EG. The pump could pump less water to maintain the same pressure. Conversely, open up the gate and the pump must pump more water to maintain the same pressure. Pressure can be conceived as a potential difference--say in the height of a water tank.
4. Current is flow of charge. For our purposes it is the flow of ions.
3. All this requires the input of energy: pump water up, pump charge out.
1. by elevating a water tower, pumping water, or adding a battery to the circuit. The system's tendency is to flow to a state of no potential difference.
4. Draw axon.
1. Lipid bilayer (phospholipids, hydrophilic head, hydrophobic tail.
2. Heads attracted to polar medium, tails to each other to form a sheet that folds over into a tube.
3. Na+ Cl- out (a/b concentration of seawater), K+ A- inside. resting potential.
4. Maintains resting potential -55 mV.
5. ion channels Na+, Cl-, K+
6. Na+, K+ Channels are normally closed.
7. Measurement of voltage (giant squid axon-large axon, small squid)
8. The axon contains a membrane that maintains separation in the concentrations of Na+, Cl-, K+. The extracellular fluid, like seawater, is rich in Na+ and Cl-.
9. Slight permeability to Na+ (some channels are open).
10. There is free flow of Cl- (These channels become important in benzodiazepines, barbiturates, and ethanol). Ignore for now, will return to them later.
11. The Na channels are activated by voltage. Some are open at resting potential, more are open as membrane becomes depolarized.
12. With small depolarization, there is some influx of Na. and corresponding efflux of K+. Ultimately this would result in no change in potential.
13. Energy separates the charge by maintaining the different concentrations in Na and K+ (3 Na+ out for 2 K+ in).

Action Potential.

1. The shape of the action potential.
1. Draw Potential vs time: threshold, hyperpolarization, depolarization, action potential, refractory period.
2. All or none, frequency constrained, partly, by refractory period.
2. Na channels open.
1. Voltage gated.
3. How do we know? (From. Nichols et al.)
1. A.P. first described in 1849, understanding began in 1949
2. "Soup vs sparks" characterized debate in early half of century (from Gordon Shepard, auvetmed, 17 feb 98.).

1. Hodgkin and Huxley, Hodgkin and Katz.
1. Depolarization causes voltage-gated Na channels to open.
1. Slight depolarization->only a few open. Then returns to resting potential.
2. Larger depolarization-> many open->more depolarization->more open-> more depolarization-> more open and so forth.
2. Na channels close, stopping the Na influx. (Voltage gated)
1. At peak, other voltage-gated Na channels (on inside) close, blocking Na+
2. The inside channels are unaffected by TTX and STX: receptor specificity.
3. Na involved in peak of A.P., and in rate at which the peak is approached.
3. Meanwhile K+ channels open more.
1. K+ to flow out, seek K+ equilibrium potential.
2. Remain open through absolute refractory period
3. Thus, voltage-gated K channels have been opening slowly and the peak time to open is shortly after the Na channels have been opening, and about the time the Na channels have closed.
4. Meanwhile, Cl flows in because channels have not changed. This helps re-establish resting potentials.
5. Na channels are closed by a separate gate that maintains the absolute refractory period.
6. Return toward resting potential, and beyond (K+.)
4. Refractory period. (absolute, relative)
1. allows travel in one direction
2. makes rate of firing related to intensity. (more intense stimuli can overcome relative, but not absolute, refractory period).
3. Propagation. Influx of Na+ diffuses along axon bidirectionally, refractory period behind prevents back propagation.
5. Role of myelin
1. Insulation.
2. Saltatory conduction.

Synapses

1. Draw simple NS, sensory afferent to motor efferent.
1. o-----< o------< o----<
2. Combination of APs.
1. Excitatory post-synaptic potential. EPSP, (Na+)
2. Inhibitory post-synpatic potential., (K+, Cl-)
3. temporal summation, spatial summation
3. Different classes of receptor action.
1. Iontropic. Attach directly to an ion channel.
2. Metabotropic. Ion channel removed from receptor.
4. Properties and examples of ionotropic.
1. Fast, short lasting, and simple. (msec resolution)
2. Glycine, glutamate, GABA, nicotinic ACH
5. Metabotrobic or (sometimes: second messenger.) Slower, longer lasting, more comlex.
1. "first messenger" is the neurotransmitter.
2. This stimulates adenylate cyclase (through guanine triphosphate), and adenylate enzyme that facilitates the formation conversion of ATP (adenosine triphosphate) to cyclic AMP.
3. Cyclic AMP is the second messenger. As long as it is available, it activates a protein kinase that opens an ion channel and produces a post-synaptic potential.
4. Cyclic AMP is broken down by enzymes called phosphodiesterase inhibitors.
5. Some receptor subtypes are adenylate cyclase inhibitors, and therefore inhibit the metabotropic.
6. Caffeine inhibites phosphodiesterase.
6. Properties and examples of metabotropic
1. Seconds to minutes to operate
2. Modulators.
3. More complex.
4. May be involved in rf pathways, e.g. (KSJ)
5. Muscarinic ACH, epinephrine,

Anatomy I

1. Principles of organization
1. High degree of order
2. Modularity
3. Structure and function interact
2. Nervous system
3. Central: Brain and spinal cord.
1. Brain
2. Spinal Cord
4. Peripheral
1. Autonomic

1. Somatic

1. Terms:
1. rostral/caudal, dorsal/vental, etc.
2. Views: sagittal, coronal, horizontal, etc.
2. Spinal Cord
1. Cenral gray, peripheral white.

Dorsal root (sensory)

1. Ventral root (motor)
2. Discovery of distinction between dorsal/ventral roots.

1. Blood and fluid.
1. General picture. Brain sits in fluid, bathed by CSF which flows around and through the brain. Sits on top of spinal cord and cortex envelops it. Protected by skull and meninges.
2. Blood fed through two principle arteries (vertebral/caudal, internal carotid/rostral).
3. Veinous drainage. Driven by pressure. Some veins can be bidirectional..
2. Menenges (singular=meninx).
1. Figure 4.6 Connnective tissue in CNS.
2. Dura mater (hard mother.) protective
3. Arachnoid membrane membrane. wedlike apperasnce. Provides some structure. CSF circulates through here. Cerebral arteries also flow through this area.
4. Pia mater (pious, or delicate mother). More flexible, follows all convolutions.
5. Peripheral nervous system only has the dura mater and pia mater. Arachnoid membrane not there.
3. Cerebral spinal fluid and ventricular system.
1. Fig. 4.7 CSF and ventricular system. Brain floats in this. Fluid cushion. Also regulated ionic environment.
2. Choroid Plexus. Dense network of capillaries that secretes a/b ½ liter cerebral spinal fluid. In all the ventricles. Weak place for BB barrier.
3. There is a blood-CSF barrier that is usually synonomous with blood-brain barrier since CSF is in equilibrium with extracellular brain material.
4. CSF formed in lateral ventricles (1 and 2), flows into 3rd, then through cerebral aquaduct into 4th ventricle. Leaves 4th ventricle through subarachnoid space, (1,2-->3-->4-->blood) flows through herniations in the dura mater into superior sagittal sinus and drains into veins.
5. Half-life of replacement is 3 hrs.
6. Hydrocephalus. Blockage of CSF. Can be treated by inserting a shunt and draining into Anatomy II: The brain abdominal cavity.

ANATOMY II: DEVELOPMENT OF THE BRAIN

1. Development. Neural tube, then forebrain/midbrain/hindbrain surrounding what becomes ventricles. Then further detail.
2. Some details from Thompson, 1993.
1. Over the nine months of development the human embryonic brain gains neurons at the rate of 250,000/min. Note, begins with a single split into two from the fertilized eg.
2. There are upwards of 100,000 genes in human DNA and about 50,000 are active in the CNS
3. Events important for the development of the brain:
1. Induction is the general principle believed to underlie development.
2. Neurons initially develop within neural plate and multiply rapidly.
3. At some point they stop dividing and migrate to their ultimate destination. Migration triggered, somehow, by the termination of mitosis. Radial glia guide this.
4. Early in development one can see beginning of forebrain, midbrain, and hindbrain forming around three chambers, which will become ventricles 1,2,3 (forebrain), cerebral aquaduct (midbrain), and hindbrain (4^th ventrical).
5. forebrain -> telecephalon (endbrain), diencephalon (interbrain)
6. midbrain-> mesencephalon (midbrain)
7. hindbrain->metencephalon (afterbrain), myelencephalon (marrowbrain).
8. further differentiation takes place through develoment.
4. Variation and selection in neural development
1. axonal growth is guided by physical and chemical factors.
2. Growth cones
3. chemotaxis permits a terminal button to find the appropriate receptor to form a synapse.
4. Selection and pruning. In order to survive, a synapse needs to be active. Importance of early experience, since this pruning takes place throughout childhood.
5. cerebral cortex:
1. begins as a single layer, a few cells thick. the "geminal zone." When a cell stops dividing it moves up to another layer.
2. Some of these cells them move up another layer.
3. This appears to move in waves.
4. Radial glia cells appear to guide this. (Mercury damages it)
6. To find each other:
1. Chemical guidance. Growing end of an axon has a special structure called a growth cone.
2. To sort out connections. Many more connections are present initially than ultimately. Sorting out takes place by death.
7. Experimental design.
1. Describe events in normal animal
2. Describe events after experimental manipulation
3. Analyses of events in vitro

1. Forebrain

1. Telecephalon.
2. diencephalon. Between mesencephalon (midbrain) and telencephalon. Thalamus and hypothalamus. .
1. Mesencephalon (Midbrain, surrounds cerebral aquaduct)
1. Tectum, (roof)
2. Tegmentum (Covering)
2. CNS Hindbrain, Surrounds 4th ventricle.
1. Metencephalon (behind brain).
2. Medulla, (some books also call myelencephalon). Most caudal portion of brain stem. Lower portion is rostral end of spinal cord.
3. MRIs to show brain sitting in the head.?
4. Cortex Transparency 20
1. Longitudinal fissure
2. Corpus callosum
3. Central Fissure
4. Lateral Fissure
5. Precentral Gyrus (motor). Motor homunculus
6. Postcentral Gyrus (sensory) Sensory homunculus.
7. Frontal, parietal, temporal, occipital lobes.
8. Transparency #1 to show evolution of cortex.
9. Transparency from Graphics book to show relationship of brain/body mass.
5. Laminar structure of cortex
1. Layer I. Superficial, few neuronal bodies, glial cells,, axonal processes, parallel to pia mater
2. Layer II Outputs. Densely cellular. mostly small, pyramidal
3. Layer III. Outputs. Larger pyramidal.
4. Layer IV. Stellate cells, afferents from thalamus, big in sensory areas.
5. Layer V. Largest pyramidal. Outputs to striatum, brain stem, spinal cord. Betz in motor areas.
6. Layer VI. Project back to thalamus.
6. Columnar structure.
7. Lateralization of Function.

1. Longitudinal symmetry
2. Brain lobes, connection by corpus callosum
3. Connection of eyes. left visual field to right brain
4. Speech is driven in right-handed people is driven by left hemisphere.
5. Experiments with split-brain.

1. Anatomic, functional, and neurochemical distinctions.

METHODS.

1. Lesion and ablation (intentional and accidental).
1. Logic: render neurons inactive, look for alterations in behavior.
2. Approach: Position brain precisely. Make surgical knife cut, or insert cannula and deliver lesion.
3. Control: sham lesion.
2. Permanent techniques.
1. Knife cut
2. Electrolytic lesions
3. Chemical lesion
3. Temporary lesions.
1. KCl (not in book, not covered)
2. Colchicine (slow down axoplasmic transport of NT).
3. Cryogenic cooling.
4. Histological techniques
1. Goal: locate site of lesion, or study structure of a region of the nervous system.
2. Steps:
5. Stains.
1. myelin (Weil stain)
2. cell body (cresyl violet gets nissl substance in cytoplasm.)
3. membrane: golgi stain. outlines full cell, but only a fraction of them.
4. Methelene blue (DNA/RNA in Nissl substance, so gets cell bodies. Not specific to neurons. )
5. Golgi stain. Outlines full cell, but only a fraction of them.
6. Nissl stain. Attracted only to Nissl substance, containing RNA, DNA, that encircles nucleus. So highlights cell bodies. Useful for doing cell counts. Not selective for neural cells.
7. Autoradiography.
6. Tracing neural connections: Anterograde.
1. From dendrites toward cell body and toward terminal button. (Moving forward, efferent to site of administration).
2. Apply close to dendrites or cell bodies. Transported toward axon. Takes a few days.
3. Phaseolus vulgaris leukoagglutinin (PHA). A kidney lectin (lectin is a protin that binds to a specific cell in immune system. )
4. Immunocytochemical methods.
7. Tracing neural connections: Retrograde, from nerve terminal toward cell body (afferent to site of administration).
1. Apply label (e.g., flurogold/flourescent) close to terminal button . Wait a few days. Look for cell bodies under microscope.
2. Horseradish peroxidase. Taken up in terminal button, migrates to cell body.
8. Recording and stimulating neural activity.
1. Electrophysiological recording.
2. Localizing neuron activation.
3. Microdialysis. (measure extracellular levels of neurotransmitter).
4. Chemical stimulation, e.g., reverse microdialysis. cannulae injection.
5. Electrical stimulation of section of brain.
9. Neurochemical methods.
1. Localize transmitters in brain.
10. Imaging techniques.
1. CAT
2. MRI
3. PET (uses 2-DG).
11. Genetic studies.
12. Behavior-chemical interactions-at the whole animal level.

Comparative and Evolutionary Perspectives.

1. What is the problem that must be solved?
1. There are many different types of organisms on the planet. Many look somewhat alike: Sparrows look like other sparrows and snails look like other snails. Others look very different. Sparrows look kind of like finches but not at all like snails. Moreover, on close examination, individual sparrows differ slightly in coloration, beak size, weight, ....The similarities and the differences must be accounted for.
2. A scientific account will accommodate all that we know.
1. The similarities among dogs are found in many elements of structure (legs, snout, brain, spinal cord, tail) and function (social, carnivores, live birth, nurse). Nevertheless, individual dogs differ, sometimes subtly, from one another.
2. There are systematic ways of classifying these into
3. There are at least three general principles that must be accounted for by a general theory. Note: Amer Heritage. Theory: 1) Systematically organized knowledge applicable in a wide variety of circumstances, esp, a system of assumptions, principles, and rules of procedure devised to analyze, predict, or otherwise explain the nature or behavior of specified phenomena. . . . 4) an assumption baed on limited information or knowledge; a conjecture. < Greek: theoros, spectator; probable from thea, a viewing and oros, seeing. Note the empirical derivation!
1. Individuals of a given species are not identical. This was a problem to solve, but now variation is a crucial component of natural selection. Indeed, variation itself may have been selected.
2. Some of this variation is heritable. Height for example or the ability to speak. But the ability to speak English is not.
3. Not all offspring survive (says Rosen..., perhaps "leave descendents" is better): some die, some reproduce. Note the distinctions: we survive long after our offspring have produced offspring. But spiders are eaten by their offspring and, in the case of some males, by their mate. What matters is leving offspring.
4. Two broad forms of evolution have been identified.
1. Convergent evolution: a process that produces a resemblance due to convergence rather than common ancestry...an "analogy".
2. Homology. Resemblance based on common ancestry, but while serving different functions. e.g., simmilar forelimb structures serving as an arm, foreleg of a dog, flipper of a seal, and wing of a bat. All contain similar bones: humerus, radius and ulna, and the bones forming hands and fingers.
5. Structure and function are often correlated.
1. But note, with correlation, causation is hard to determine.
6. Be able to list the commonalities among vertebrate nervous systems:
1. Development from a hollow, dorsal tube, bilateral symmetry, segmentation (pairs of spinal nerves from each level of cord), hierarchical control (from brain), separate systems (e.g, central/peripheral, symp/parasymp), localization of function.
7. Be able to compare and contrast N.S. of vertebrates with that of molluscs and insects.
1. basic plan: both have one and most invertebrates have some sort of central n.s....but not all
2. Brain. Not all invertebrates have one, but evolution tends to press toward central control.
3. Number of neurons. Vertebrate: many devoted to info processing. Invertebrate brains have fewer, more complicated, and larger ones. So some info processing takes place in the neuron.
4. Identifiable neurons: found in invertebrates, very few cases in vertebrates.
5. Ganglion structure. more reliance on distributed ganglia in inverebrates. The structure is that of a outer rind consistingof monopolar cell bodies and an inner core consisting of the extensions of cell bodies forming a "neuropil" (network of axons and dendrites.
6. Axons and neuronal conduction. Many mammalian axons have myelin --> faster. Perhaps b/c mammals are so big. Many invertebrates have a few giant axons (squid, crawfish) mediating escape responses.
7. Structural changes. Invertebrates undergo impressive, large changes (metaphorphosis). Vertebrates changes are less impressive.
8. Location. Vertebrate--in bony skull. Inveterbrate--in many, in stomach (note Abdominal nervous system in mammals).
8. Note similarities in brain structure. transparency.
9. Note brain weight/body mass ratios among diferent vertebrates.
1. Slope describes relationship between body mass and brain mass.
2. Intercept: encephalization factor. Larger factor --> larger relative brain size.
3. The following encephalization factors come from Schmidt-Nielson. They were originally reported for a regression of brain mass in kg vs body mass in kg. The factors used in the text gives wrong answers for brain size...for example. it says that the human brain is 0.71*(body mass)^.69 = 13.3 kg or 13.3 grams (they are not clear as to what units they are using) either is incorrect. 13.3 kg = 29 lbs. 13.3 gm is about 14 paper clips.
4. Note that there is a basic amount of brain function req'd just to function. So over that provides additional senses, motor control, plasticity.

Drugs.

1. Dose/effect curve.
1. ED50, LD50, Margin of safety/therapeutic index
2. LD50/ED50 vs LD1/ED99
2. Tolerance and sensitization.
1. Sensitization.
2. Tolerance. Decreased sensitivity to a drug due to repeated administration.
3. Behavioral tolerance.
4. Withdrawal. Closely linked to tolerance and to drug abuse.
3. Placebo effect,
1. Placebo: an inert substance given in lieu of a physiologically active drug.
2. Used experimentally as a control. Often used as a control used when testing for therapeutic effects of a new drug.
3. Can be a large effect.
4. Time course curve. Intensity of effect (or amount, or concentration) vs time.
1. Plot ascending and descending curve with horizontal line showing threshold for effect.
2. T0 = time of administration
3. T1 = onset of action
4. T2 = peak effect
5. T3 = offset of action (mention acute tolerance here).
6. Absorption, distribution (can include the ascending and first phase of the descending curve) , elimination.
5. Kinetics.
1. Pharmacokinetics. "the factor influencing the magnitude of drug effect by determining the amount of drug at various sites in the body as a function of time" (Levine).
2. The half life.
6. Routes of administration.
1. Note time course for i.v., inhalation, and oral.

1. Major events in neurotransmission
1. Synthesis of neurotransmitter, formation of vesicles
2. Transport down axon
3. Storage in vesicles
4. Release of NT by action potential (Ca++ )
5. Interaction with a receptor (excite or inhibit)
6. Separation of NT from receptors
7. Stop action
8. Autoreceptors.
9. Presynaptic receptors.
10. Pharmacodynamic tolerance.
2. Neurotransmitters
1. Acetylcholine
2. Biogenic amines (or monoamines)
3. Amino acids.
4. Adenosine
3. All action described in terms of receptor.
1. Agonist vs antagonist
2. Direct vs indirect.
4. Affinity.
5. The effect of a drug is related to the amount of a drug at a site of action. The proportion of a dose actually contributing to a drug's effect is influenced by:
1. The rate and extent of absorption from the site of application
2. The rate and extent of tissue distribution (e.g., lipophillicity)
3. The rate of biotransformation to active or inactive metabolites
4. The rate of excretion.



6. Norepinephrine receptor and stimulants (cocaine/d amphetamine).
1. Alpha methyl para tyrosine (AMPT). Blocks synthesis of dopa from tyrosine.
2. Reserpine. Inhibits storage (makes vesicles "leaky").
3. d-amphetamine. stimulates release of NE (and DA). increases alertness and arousal. Rebound depression, b/c not replaced rapidly enough. One evidence for role of catecholamines in depression.
4. Haloperidol. blocks receptor.
5. cocaine. Tricyclic antidepressants. Block reuptake.
6. MAO inhibitors. Block degradation
7. Clonidine. Stimulate presynaptic receptor. Acts like a lot of NT is there, therefore acts as an antagonist postsynaptically since inhibits release. Attempted in treating cocaine (unsuccessful)
7. Book mentions nicotine, lsd, Ergot (grain mold) as serotonin agonist, Salem.

Some synthetic pathways.

1. Acetyl CoA + Choline ^CAT--> ACh + CoA
2. ACh ^AChE-> Choline + Acetate
3. Tyrosine -> l DOPA -> Dopamine -> Norepinephrine-> Epinephrine.
1. ACh synapse .
2. Dopamine synapse
1. D1: post-synaptic, increase 2^nd messenger cAMP
2. D2: pre and post-synaptic, decrease 2^nd messenger cAMP
3. Glutamate
1. Ionotropic
2. Metabotropic
3. Require both A.P. AND receptor occupation.
4. Four properperties:
4. GABA (Gamma-aminobutyric acid).
1. GABA_A receptors. different sites of action
2. benzodiazepines (and alcohol?): book narrative says these are linked. figure suggests barbiturate.

Sensory Systems: General

1. General layout
1. Reception--Physical interaction with receptor-- e.g., odorant molecule, audition, pressure.
2. Transduction--physical energy to electrical energy.
3. Coding--frequency and difference.
2. Transducers convert some form of energy into electrical energy that the N.S. can use.
1. Mechanical (hair cells, pressure)
2. Acoustic (also hair cells)
3. Chemical
4. Thermal
5. Electromagnetic
3. Example: Pacinian Corpuscle.
1. Bare nerve fiber, specially designed so that bending it opens ionic (Na+) channels
2. Onionlike layers around free-nerve ending to cushion.
3. depolarize--generate action potentials.
4. Record from fiber
5. Physical structure (not neural circuitry) makes it more sensitive to slow, transient touch.
4. Receptive field.
1. neuron in somatosensory cortex connects to that Pacinian corpuscle. Receptive Field for that neuron is the area of skin serving that P. C.
2. Sensitivity or two-point threshold is related the density of pacinian corps--or nerves which, in turn, is related to amount of cortical surface area devoted to area of skin.
5. Texture.
1. Pacinian: highest sensitivity: 250-300 Hz (rapidly adapting, pressure, vibration).)
2. Vibration sensitivity.
3. Detect texture by moving finger.

Vision.

1. Physical stimulus is "light".
1. Part of E.M. spectrum--show transparency
2. Varies in amplitude and frequency (wavelength)
3. Visible light, about 400 to 750 nanometers
4. High energy = high frequency = short wavelength
5. quantal (photon) vs wave.

1. Characteristics
1. Intensity
2. contrast
3. color (hue, saturation, brightness).
4. Dynamic range (photopic, scotopic)
5. Detection of form.



2. General layout of visual system. Eye-> optic nerve -> chiasm -> tract -> LGN -> occipital cortex.
3. Eye.
1. Iris (muscle forming a hole called pupil)
2. Lens
3. Eye muscles Rapid. No afferents.
4. Cornea. Clear covering
5. Photoreceptors on fovea: rods and cones
6. Blind spot.
7. Choroid Plexus: black lining, nutrition. Holds photoreceptors. Provides photopigment.
4. Transduction at photoreceptor..
1. Rod cells contain a photopigment. Rhodopsin (rose opsin). Unbleached (in dark) had deep purple hue. In light turns pale.
2. Rhodopsin consists of 11 cis retinal and (rod) opsin. Light causes retinal to straighten out and detach from opsin, producing all trans retinal and opsin.
3. Causing hyperpolarzation from -35 mV to -55 mV (K+ Nernst potential).
4. Graded potential of rods and cones discovered by Tomita.
5. Structure of the Retina and the visual pathways.

Photoreceptors

|

| Horizontal

Bipolar Cells

|

| Amacrine

Ganglion Cells

1. Intermezzo: series of stages for vision:
1. Light absorbed by rhodopsin
2. Isomerization of retinal
3. Block Na channels
4. hyperpolarize rod or cone
5. Release synaptic vesicles
6. Graded (generator) potentials in amacrine, bipolar, horizontal
7. Action potentials in ganglion cells:
8. Integration to produce contrast center/surround RF. Physical stimulus.
9. Light. Wave (amplitude, frequency/wavelength)
10. Quantum. packet of some energy, corresponding to wavelengtn.



2. Color
1. Trichromatic/Young-Helmholtz
2. Note experiment.
3. Hering. Opponent processing.
3. Single unit recording in the visual system.
1. Use electrode, monitor firing rate, then find receptive field, then find optimal stimulus.
4. Optimal stimulus in LGN, center-surround.

1. Cell types in LGN. X, Y. Transparency.
2. Parvo/magnocellular distinction.

1. Visual processing in visual cortex.
1. Feature detectors: isolate features of vision.
2. Simple cells. Stationary bar or edge at particular angle in particular part of RF
3. Complex. Larger RF, particular pattern moving in a particular way at a particular speed or stationary bar anywhere in R.F. .
4. Hypercomplex. Similar to complex, but with strong inhibitory region.
5. Grandmother cell
6. Visual agnosias. See table in KSJ..
2. Structure of primary visual cortex.
1. Orientation columns
2. Laminar structure.
3. Pull together the visual pathways.
1. As Carlson points out, there are separate areas for color (in primates and some other species), form, position, and movement.
4. Dorsal stream.
1. Both (dorsal and ventral streams) originate in striate cortex, diverge in extra-striate cortex.
2. Dorsal stream is 'where' system.
3. Turns upward (dorsally) ending in ctx of posterior parietal lobe.
4. mostly magnocellular input, but some parvocellular too.
5. Ventral stream
1. "What" system.
2. Also originates in striate ctx, diverges in extra-striate ctx.
3. about ½ magno, ½ parvo.
6. Pull together parallel visual pathways.
1. Parvo- and magnocellular both go to Layer 4C of area V1 (Vee-one) (primary visual cortex) and there the pathway branches into 3.
2. In general they handle the following features: color (originating from parvo); fine detail (originating mostly from parvo); broad form (originating largely from magno); and motion, depth, location (mostly from magno).
7. Lesion studies
1. V1: lose color sensitivity. Also responsible for orientation, eye dominance.
2. V4: color and form perception. Lesions diminish color perception.
3. V5. movement.
4. Inferotemporal ctx. (ventral stream)
8. Lateral inhibition.

Motor systems

1. Motor system. General picture.
1. Motor system. Efferent side. What questions would one want to ask:
2. General Organization of sensorimotor system organized so as to initiate a motor act (ctx), orchestrate the contraction of muscles to pull it off (basal ganglia, "motor" loops), send those instructions to the appropriate neuron in the primary motor cortex, which sends instructions down spinal tracts, with a branch to the cerebellum stating the intent, monitor the muscles to ensure that they do as they are told at the level of the spinal cord and in the cerebellum. The consequences of motor acts figure in, too, through midbrain structures close to the substantia nigra and that probably make contact with the "cognitive" loop of the basal ganglia.
2. Muscles
1. Smooth, internal organs.
2. cardiovascular, heart.
3. Striated, Slow-twitch, slow, little fatigue, less vigorous contraction.
4. Striated, fast-twitch, rapid, fatigue readily, vigorous.
3. neuromuscular junction.
1. motor unit--neuron and muscles it innervates.
2. eyes, one neuron, only a few fibers.
3. biceps, one neuron, hundred fibers.
4. Acetylcholine receptor at the neuromuscular junction
1. Nicotinic cholinergic receptor.
2. Stimulated by nicotine.
3. Ionotropic
4. Release of Ach is promoted by alpha bungarotoxin (a snake venom), black widow spider venom.
5. Release of Ach blocked by botulinum toxin.
6. Nicotinic receptors blocked by rabies virus, curare.
7. Acetylcholinesterase is inhibited by soman (irreversibly) or physostigmine (irreversibly).
5. Myesthenia Gravis
1. Automimmune
2. Decrease ACh receptors--weakness
3. Rx--replacement, ACHE (a pesticide)/discuss mechanism
6. Stretch reflex/reflx arc.
1. Starting at muscle spindle, aferent impulses are conducted to termnal buttons in gray matter of spinal cord. These terminal buttons terminate on alpha motor neuron that innervate extrafusal muscle fibers of same muscle. Maintain position of limb, postural control. Gastrocnemius muscle (large calf muscle) that goes behind the knee. When stretched, stretch reflex contracts to maintain posture.
2. Another reflex, from golgi tendon organ. Some detect amount of stretch and go central. Another forms a second spinal reflex except through a glycine (inhibitory) neurron that inhibits the efferent alpha motor neuron.. {this was the first discovery of inhibition).
3. Unilateral deafferentation (Taub). Diminished use. Preference for intact limb. Force use-> learn to use it. Application to stroke victims.
7. Descending pathways. Two types: dorsolateral and ventromedial. Named for where cell bodies lie in the spinal cord.
1. Traditional distinction: pyramidal vs extrapyramidal.
2. General picture: Current distinctions involve dorsolateral and ventromedial tracts. Each has a corticospinal component and a cortico-brainstem-spinal ( "extrapyramidal") component.

1. General picture: linear

Dorsolateral

(Distal)

CTX --------------------------------> spinal cord --------> muscle, voluntary.

CTX----------> red nucleus------>spinal cord ---------> muscle, locomotion, balance

Ventromedial (Ventral in Carlson)

(proximal)

CTX --------------------------------> spinal cord ----------> muscle, voluntary

CTX ------------> brainstem -----> spinal cord -----------> muscle, locomotor, balance

1. Some notes.

1. DL and VM pathways similar in that each has two major tracts. One direct from ctx to muscle (with a couple of synapses in between). The other makes a stop at the brainstem first.
2. "Voluntary" designation after the corticospinal is traditional. All are "voluntary" in a sense (i.e., not strictly reflexive) and all originate in cortex and susceptible to operant control
3. VM: more diffuse, axons inneverate bilaterally and across spinal segments.
4. DL: contralateral descent, unilateral control, specific spinal segments, distal limbs.
5. Carlson (and most others) makes some finer distinctions in the Ventromedial pathways. Note these are in the Ventromedial cortico-brainstem-spinal tracts. .
6. Corticobulbar (bulbar=medulla). similar to corticospinal, but for cranial nerves.
1. Ventromedial pathways. "maintenance of erect posture, to integrated movements of body and limbs such as orienting movements, to synergistic movements of individual limbs and to directing the course of progression." (Kuypers, 1985, copied from Shepard's text.)
1. Ventromedial cortico-brainstem-spinal tract.
2. Ventromedial pathways involved with posture. Lesions --> postural deficits. Loss of control over trunk and proximal limb muscles. Monkeys could stand only with great difficulty.
3. Ventralmedial corticospinal. ipsilateral. orignate in trunk and upper leg regions of primary motor cortex. descend to appropriate regions of spinal nerve and emerge to muscles in trunk. These pathways are responsible for trunk, neck, proximal limb muscles.
4. dorso lateral tracts: finer control. Control of extremities..
2. How do we know this? Anatomy had been described for some time. Function described in series of experiments involving lesions of descending corticospinal pathways (ipsilateral and contralateral).(Lawrence and Kuypers, 1968).
1. Lesion dorsolateral corticospinal tract (left and right) in medullary pyramids. V-M. remained intact.
2. Then, 1/2 monkeys, unilateral lesion of dorsolateral corticorubral spinal tract.
3. Other half. lesion all ventromedial pathways, only corticorubral spinal intact.
3. Basal ganglia.
1. Input to striatum (caudate/putamen)
2. Outputs are globus pallidus and substantia nigra.
3. Interconnections are inhibitory
4. Motor loop (motor/sensory ctx->putamen->GPi (caudal-ventral), Snpr -> thalamus). Lesion-> motor effects. (Parkinson's disease)
5. Cognitive loop (frontal assn ->caudate->GPi (rostral/caudal), Sn/pr (rostro-medial.) Lesion: reversal learning, sequences, Huntington's disease.)
4. Linear approach, to help think about disorders of motor loop. Note, does not strictly map onto above figure, b/c a nigral/striatal loop is represented here:

Inhibit Inhibit Inhibit Excite

Substantia Nigra -> caudate/putamen -> Globus/pallidus -> thalamus -> cortex -> muscle tone, bradykinesia.

1. Remove globus/pallidus: remove inhibition on thalamus, increase muscle tone, increase bradykinesia.
2. Remove caudate/putamen: remove inhibition on GP. Decrease muscle tone, decrease bradykinesia (too much movement).
3. Remove SN. Like removing GP (on first approximation).
1. Huntington's Chorea
1. Genetic disorder/dominant gene, 50% chance of inheir.
2. Doesn't appear until after 40's (after age of reproduction, usually.)
3. Damage to caudate and putamen. Cholinergic and GABAergic.
4. Motor incoordination/spasticity/involuntary muscle movements (involuntary is characteristic of B.G.), cognitive loss-retardation, dementia. death within 15-20 yrs. about 10,000 cases in US.
2. Parkinson's disease
1. Resting tremor, slow movement, rigidity, little cog. loss, but difficulty doing more than one thing at a time.
2. Loss of DA neurons, esp in S.N., in nigra/striatal loop.
3. Appears when 60-90% of S.N. is depleted. This may occur through life. Insult in youth may lead to earlier onset.
4. Rx is replacement therapy--l DOPA. precursor to dopamine. Get nigral-straital connection going again.
5. Neurolepetics. Block DA. Causes parkinsonian symptoms. Alleviated with benzotropine (cholinergic agonist).
6. Chronic blockade of DA: receptor supersensitivity. Over-activity of SN. Too much movement. Tardive dyskinesia.
3. MPTP methylphenyltetrahydropyridine
1. 30-40 Y.O. drug addicts on West Coast
2. Detective story. A group suddenly came down with P.D in 1983. Traced to one source of supply and ultimately to one underground chemist.
3. Produces signs and symptoms identical to P.D. in all primates.
4. Points to environmental cause.
5. Research prompted by it.
6. MPTP --> MPP+ in presence of MAO.
4. Tardive Dyskinesia/nigral-striatal loop.
1. Halopridol: blocks DA receptors. Note: benztropine-> anticholinergic. Blocking Da releases inhibition on the Ach--they become overactive, benz inhibits instead.
2. P.D.: Da neurons die.
3. Huntington's: ACh neurons die. Decreases inhibitory output b/c of GABA. S.N. becomes too active.
4. Tardive dyskinesia. Increases dopamine sensitivity through denervation supersensitivity.



5. Cerebellum
1. Among the oldest structures phylogenetically.
2. Overall structure:
3. Draw on board:
4. Lateral zone, intermediate zone, vermis, flocculonodular lobe. Now the structures. Carlson does this anatomically, I'll do it functionally (from Neurobiology of Disease book)
5. Vestibulo-cerebellum (flocculonodular in Carlson).
6. Cerebrocerebellum. Poorly discharged ballistic movement. Impairment in highly trained movements. Poor aim.

SLEEP.

1. All species, some more than others,
2. Note amount of energy and behavior devoted to finding a safe place to sleep.
3. Transparency. Stages of sleep.
4. Resting and awake.
1. Alpha waves. Regular oscillations. about 8-12 Hz. .
2. Beta waves. irregular, low-amplitude, high-frequency.
5. NREM Sleep.
1. Stage 1. Transition stage. If awakened, sometimes report that they weren't asleep. Theta waves(3.5-7.5 Hz). irregular, jagged, low in voltage.
2. Stage 2. K complex. (abrupt high-magnitude, low-frequency waveform (like an electric sigh).
3. Stage 3 and 4 (Slow-wave sleep/SWS). Can be hard to distinguish from one another, but stage 4 is much more dominated by delta activity (very high amplitude, low-frequency (< 3 Hz) activity. This period may permit brain to rest.
4. Sleep spindles. Short-bursts of activity (low-magnitude, 12-14 Hz) at all stages.
6. REM sleep
1. Eugene Aserinsky and Nathaniel Kleitman. Studying EEG and alertness in children. 1953.
2. EEG like awake. ("desynchronized").
3. Muscles limp. Lack of muscle tonus.
4. Rapid eye movement.
5. Vaginal secretion/penile erection.
6. Narrative, vivid dreams. (During slow-wave can be more static, sometimes nightmares).
7. all mammals and birds.
8. deprivation and rebound.
9. Sleeping pills (barbiturates, benzodiazepines).
10. Clinical depression-> too much REM, little stage 4. (see end of book).
7. Basic rest-activity cycle (BRAC).
1. Cycling between REM and NREM.
2. Kleitman (1961) pointed out others, including performance on vigilance tasks, eating, drinking, heart rate, oxygen consumption, stomach motility, urine production.
8. Dreams
1. Housekeeping: sorting and organizing? (narrative aspect is a secondary byproduct).
2. Secret desires? (narrative is of primary importance.)
3. Flushing the synapses?
9. Sleep as restorative process? Human studies.
1. Sleep deprived humans.
2. Little difficulty with physical activities.
3. No change in physiological stress (i.e.changes in cortisol and epinephrine which result from chronic stress).
4. With severe deprivation, e.g. staying awake for 264 hours (11 days) in order to set a record, only slept for 15 hours and he was fine.
10. Animal studies.
1. Yoked control procedure.
11. Exercise and sleep.
1. Even bed-ridden individuals sleep, similarly to normals.
2. A relationship may exist between body-temp. elevation and sleep-and exercise elevates both temp. Any elevation in body temp during the day increases sleep that night. (note experiment in book, do not cover in class).
3. Mental activity. Cortical activity, even that produced by applying a vibrator to a finger, produced more delta activity in that portion of the brain at night.
12. Chemical control of sleep.
1. Benzodiazeines.
2. aspirin or ibuprofen.
13. Neural control of arousal.
1. Brain stem reticular formation: general arousal (NE).
2. Basal forebrain. (ACh)
14. Cycling of REM/NREM sleep. Control in Pons (predator/prey?).
1. Note figures 8.11, 8.13, 8.15.
2. Stack them up.
15. Acetylcholine.
1. Paribrachial area of pons
2. Active just before and during REM sleep. may trigger onset of REM sleep and efferents may inhibit ARAS. or cortical structures. Activity leads to PGO waves, REM, cortical activation.
3. ACh activity from magnocellular regions produces paralysis of descending motor fibers.
4. ACH also inhibits Dorsal raphe and Locus Coeruleus.
16. Norepinephrine and Serotonin.
1. Dorsal raphé.Raphé contains much serotonin.. Once thought to be primary NT involved in onset of sleep. Health food stores sold tryptophan, precursor to serotonin. Not real effective. Tryptophan also in milk products (warm milk before bed?).
2. Raphé means seam. System is located medially in brain stem, close to a line joining halves of the hindbrain.
3. Locus Coeruleus. catecholamine. efferents go widely to brain. Apparently suppresses sleeep. Activity falls to zero (actively inhibited) during REM sleep.
17. General points.
1. Cycling of sleep/arousal and of REM/NREM sleep is distributed across the brain.
2. No central executive mechanisms, probably, but rather interactions of excitation and inhibition.
3. Neurochemical processes account for actions of drugs.
4. Such an elaborate process, that occurs across many species has to be important.
18. Neurochemistry.
1. 5-HT agonists.
2. 5-HT antagonists.
3. NE. Active when awake, less active when asleep.
4. Acetylcholine.
5. Caffeine decreases stage 4 a lot.
6. Aging. Decreases acetylcholine and REM
7. Depression.
8. Amphetamine withdrawal (REM rebound).

Basic Rest/Activity cycles.

1. First different diurnal cycles, then about sleep.
1. Circadian rhythms (daily)
2. Ultradian (faster than a day).
3. Zeitgeber.
4. Importance
2. measurement.
1. Simply note when go to sleep or awaken.
2. Activity. running wheel, attach an actimeter, etc.
3. Type of information. Gross activity. Elevator example. Look at photocell breaks on elevator to get activity of Haley Center.
4. Could get daily rhythms, hourly rhythms (ultradian) rhythms.
5. Then ask what causes them. How can we produce or eliminate them?
6. Endogeneous or exogeneous? remove or add cues.
3. How does sun (light) act?
1. through eyes?
2. Curt Richter. blind rats. Then ask further, blind along optic tract. note eliminate by blinding anterior but not posterior of chiasm. Suprachiasmic nuclei is important. Fibers come from optic nerve up to SCN. not tract.
3. but still a rhythm. in humans 25 hours (recent data, more slightly more than 24 hrs). Sun marks the time but is not the whole.
4. Jet lag.
1. Going west is easier because one can sleep late.
2. Stay in the sun.
5. Shift work. Rotate through later shifts (day, evening, night) takes less time to adjust than other direction. Also lots of lights in the room.

Homeostasis

1. Feedback system
1. Open loop (no feedback) vs closed loop (feedback).
2. Negative feedback: Control signal minus output results in a new command.
3. Examples:
4. Positive feedback. Explosive.

1. Body temp maintained at a constant level. 37^o C or 98.6^o F. this set point can vary with time of day. (Drops when asleep)
2. Sensors
1. peripheral temp. receptors in skin
2. Hypothalamus
3. Homeostasis. (Walter Cannon)
3. Controlled by hypothalamus. important areas are preoptic area (heat dissipation) and posterior (head conservation). Separate controls. Sources of influence are from peripheral temperature detectors and local (hypothalamic) detectors.
1. Mechanisms of warming up: behavioral (moving to warm place), shivering to generate energy, vasoconstriction to get blood away from skin and embedded in fat.
2. mechanisms of cooling off, behavioral, vasodilation, spreading out (dog on porch), panting, sweating.
3. Local control.
4. hypothalamus. Afferents from peripheral temp receptors embedded in skin. There are separate ones for warmth and cold. Efferents to autonomic, endocrine, and skeletomotor responses.

1. Fever. (Kluger, M.J. 1979) Iguana (ectotherm).
1. Place iguana on a thermal gradient, cool on one end, warm on the other.
2. Places itself in middle: 98^o
3. Infect with flu virus: positions self in warm part of gradient: gives self a fever.
4. Prevent this from happening: Ill longer, more likely to die

1. Drinking
1. Note, to maintain homeostasis need detector, setpoint(s), and effector
2. Homeostatic. Maintain constant, 0.15 M solution of solutes (isotonicity).
4. Hypovolemic

1. Starting and stopping appear to be controlled separately.
2. Note problems to be solved.
1. Food needs to be controlled and selected
2. Glucose not lipid soluble, membranes are not.
3. Food must be stored.
4. Meals neet to start and stop.
5. No way of knowing body weight.
6. Food has multiple functions: glucose, nutrients, etc.
3. Peripheral factors
1. Flavor
2. Aversions (and proclivities) show plasticity through life.
3. Respondent. Pair flavor with distress, then distress elicited by flavor. (me and gin).
4. Stomach: two stimuli
1. distention. Test, (Deutsch).
5. Duodenum
1. secretes cholecystokinin (CCK). Secretes as hormone into bloodstream when food released. Is this relevant?
6. Glucose/insulin cycle.
1. Eat --> food digested --> glucose absorbed in blood

insulin -----> enters cells (if insulin is present) and converted to fat or glycogen.

1. Summary

2. Korsakoff. severe thiamine (vitamin B1) deficiency. Thiamine required to metaboloze glucose. retrograde and anterograde amnesia.
3. Learning in Aplysia.
1. Transparency of aplysia.
2. Flaps, and siphon
3. Stimulate siphon, gill withdraws.

1. Substance Abuse.

1. Old definition of addiction: physical addiction.
1. Based on heroin withdrawal.
2. Associated with tolerance.
3. Withdrawal symptoms always the opposite of the drugs' effects.
4. Heroin->euphoria, constipation, relaxation, analgesia.
5. Heroin withdrawal-> dysphoria, diarrhea/cramping, agitation, sensitivity to pain
6. Alcohol/tranquilizers--> sedation, hypnotic actions, diminished seizures.
7. Alcohol/tranquilizer withdrawal-> anxiety, sleeplessness, enhanced seizures (potentially fatal).
8. Neither necessary nor sufficient.
9. Cannot explain first use.
10. Drug addicts undergo repeated withdrawal.
2. Current definition. Focus on common features.
1. Reinforcing properties of drugs. animal and human studies.
2. Negative reinforcement. e.g., avoidance of withdrawal.
3. Tolerance.
4. Craving/relapse.
3. Commonly abused drugs.
1. Common feature is dopamine. Necessary, but not sufficient.
2. amphetamine, cocaine, opiates, nicotine, alcohol, sedative/hypnotics, barbiturates PCP, cannabis release dopamine.

Physiological and Behavioral Tolerance

1. Discriminative Properties of drugs.
1. Three-term contingency
2. Definition of discriminative stimulus.
3. Most work done with exteroceptive stimuli. Assertion that science applies to interoceptive stimuli, as well.
4. General tactic.

1. Sedative/hypnotics.

1. Barbiturates, ethanol (and other alcohols), benzodiazepines.
2. General effects
3. Common effects:
4. Five principles:
5. Tolerance.
6. Receptor actions.
1. Ethanol is the active ingredient so as long as it is around, one is intoxicated.

New Drug Development.

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Last modified: July 10, 2002