Chronological overview

1. 1628: William Harvey; beginning of modern physiology; anatomical dissertation on the movement of the heart and blood in animals

2. 1786: Valivani; on relation between electricity in physical world and in animals; electrical stimulation of frog's nerves cause muscle contraction; current is generated by the animal, not by the potential difference between external source and the body (Volta)

3. 19th century: Johannes Műller, Justus von Liebig, Carl Ludwig, Francois Magendie, Michael Foster, Hermann von Helmholtz (conduction of nerve impulse measure)

4. 1843: Du Bois-Reymond; sensor to measure small postential differences across nervous membranes; nerve impulse is a wave-like propagation of negativity in nerve trunk; invention of galvanometer

5. 1847: Carl Ludwig; invention of kymograph (an instrument consisting of a rotating drum holding paper on which a stylus traces a continuous record) 
   
   Figure 1. Horizontal and vertical kymographs
    

6. 1860: Claude Bernard; "Introduction to the Study of Experimental Medicine"
   1. Emphasis on importance of experimentation on living animals
   2. The physical and chemical sciences provide the foundation for physiology, although it is not reducible to them
   3. The notion of "vital force" does not explain life
   4. Vivisection is indispensable for physiological research
   5. Biology depends on recognizing that processes of life are mechanistically determined by physico-chemical forces
7. 1869: Ludwig founded the Physiological Institute in Leipzig, which served as a model for medical schools all over the world

8. 1869: Foster in London taught first laboratory course as part in medicine, still influential in Britain and US

9. 1868: Eduard Pflűger founded the Archiv fűr die gesamte Physiologie in Bonn

10. 1878: Foundation of the Physiological Society and the Journal of Physiology by Foster, countering the opposition to animal experiments

11. 1887: Henry Newell Martin and S. Weir Mitchell at Johns Hopkins University founded American Journal of Physiology

12. 1904: Ivan Pavlov; Nobel Prize for work on the digestive system, discovered the conditioned reflex, central inhibition

13. 1906: Sherrington discovered the synapse and the principle of active inhibition, and interplay of inhibitory and excitatory processes

14. 1914: Brown; locomotion generated by spinal pattern generators

15. 1938: Huxley; a model of nerve axon

16. 1951: Hodgkin and Huxley; published mechanisms of nerve conduction; Nobel Prize for the theory of excitation, conduction and transmission in nerve cells by sodium and potassium ions

Sherrington

1. 1932: Nobel Prize for Physiology or Medicine

   1. Extensive behavioral experiments on decerebrated monkeys, dogs, and cats

   2. Recognition of the necessity toward physiology from structural anatomy: "study of merely visible form" to "subtler and deeper sciences"

   3. Experimental focus on simple reflex and organized action based on reflexes

2. Reflex is a functional unit comprised a sensory impulse, afferent signal to spinal or brain, conducting an efferent signal to effector organ

3. Reflex arc is composed of three separable structures

   1. Receptor

   2. Conduction

   3. Effector

4. Simple reflex constitutes the unit reaction of the nervous system although the singular occurrence of a simple reflex is probably a fiction

5. Coordination is the compounding of reflexes

6. Experiments

   1. Method: Spinalizing an animal by severing the spinal cord below the brain, application of electric stimulation to elicit a reflex response

   2. Role of receptor

      1. Adjustability of threshold of stimulation

      2. Selective excitability to certain appropriate stimulation

7. Difference between nerve trunks and reflex arcs are found during electric stimulation; without knowing the existences of afferents, efferents, or synapses, he showed that reflex arcs exhibited

   1. Slow conduction speed

   2. Less correspondence between moment of cessation of stimulus and end-effector

   3. Less correspondence between rhythm of stimulus and rhythm of end-effector

   4. Less close correspondence between intensity of input and output

   5. Resistance to single impulse, not to a sequence of impulses

   6. Irreversibility of direction

   7. Fatigability

   8. Variability in thresholds

Reflex

1. Induction and Irradiation

   1. Two subliminal stimuli elicit one response together; nonlinear temporal and spatial summation)

   2. Sequential activation of more and more responses with increasing strength

2. Precurrent reciprocal inhibition

   1. Output is sensitive to difference in input streams, but insensitive to noise which is common to both inputs

   2. Sharpens stimulus distinction when receptors are only poorly tuned
      
      Figure 2. Precurrent reciprocal inhibition; open circles represent excitatory synapses and closed circles indicate inhibitory ones

    

3. Recurrent reciprocal inhibition
   
              Figure 3. Recurrent reciprocal inhibition

Pavlov

Hull

Fentress

Easton

1. Reflexes are basic units of voluntary movements

2. Reflexes are synergies or coordinative structures

3. There is a hierarchy of reflex units where the higher the control level, the more complex the behavior

4. It is economical in coordination to use prewired relfexes rather than activation of single motor units

Philippson

Muscle and spring

1. Hill's model
   
   Figure 1. Muscle model
    

2. Linear and nonlinear springs

3. Recording a relationship between muscle force and length with central connection is methodologically challenging

   1. Control over descending signals

   2. Intact nerve interconnections

   3. Reliable recording of force-length characteristics

   4. Different for human and animal experiment

Mattews (1959): animal experiment

1. Lesion: removing upper neural structures from lower structures (muscles)

2. Electric stimulations at a distal stump at the level of lesion to the lower structures were considered as descending commands

3. Stimulations on different distal parts

4. Initially, small increase in muscle length -> small increase in passive force without a-MN help

5. At a certain length of muscle -> muscle actively increase force because of autogenic recruitment of a-MN (tonic stretch reflex: TRS)

6. Different places of stimulation -> parallel shifts of the whole curve without overlapping
   
   Figure 2. Muscle length (abscissa) and force (ordinate) relationship
    

7. The unchanged force-length (F-L) was called later "tonic stretch reflex characteristics" or "invariant characteristics"
    

Rack and Westbury (1969): animal experiment

1. Force-length relationship of isolated muscle

2. Nerve stimulation of cat soleus muscle at different frequencies

3. Intensity of stimulation shifts F-L curves in parallel

4. Electric stimulation can be seen as a setter of muscle resting length
   
   Figure 3. Muscle length (abscissa) and force (ordinate) relationship in a cat soleus muscle

Feldman (1965; 1966a,b): human experiment

1. Human muscle experiment is more challenging than animal experiment

   1. Ethics

   2. Reliable control of descending signal

   3. Joint motion is involved -> angular measures are needed: torque and angle (T-A)

2. Methods

   1. Subjects occupied an elbow joint angle against a torque by using a load or a spring

   2. Unexpected release of the load

   3. Instruction: "Do not intervene voluntarily when the load is removed"

   4. Torque (T) and angular displacement (A)

   

   Figure 4. One example of Felman's unloading experiment
    

3. Relying on the performance by subjects could have lead to the problem of reproducibility

4. However, strikingly similar results as animal experiment data

5. Different angles -> whole curve shifts = l shifts
    

   
   Figure 5. Torque-angle (T-A) relationship from Feldman's unloading experiment; solid circle on the top or the bottom of each curve indicates the initial combination of T and A, open circles represent the recorded T and A throughout the whole ROM from different load unloadings, the dotted vertical line refers to l (muscle length when a-MN recuitment starts), upper curves are from elbow flexions, lower curves are from extensions