January 25, 2025	PSY 340 Brain and Behavior Class 07:  The Concept of the Synapse & Chemical Events at the Synapse (pt. 1)

Why is an action potential slower in a thin vs. a thick axon?

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Signal Transmission in the Nervous System: Two Basic Methods

The signals in the brain are transmitted using two different methods (the first of which we studied last week)

• Along the axon the signal is transmitted electrically as an action potential.
  

• At the synapse, the signal goes from the axon terminal button across to the post-synaptic membrane (on a dendrite, e.g.,) by chemical means.

So, now we turn to understand the synapse and how signals are sent chemically between one neuron and another.

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The Puzzle of How Neurons Are Connected

At the beginning of the 20th century, Santiago Ramón y Cajal proposed that there was some type of junction between two neurons. Neurons were distinct cells. However, what was the nature of that junction?

• Did one neuron actually touch the other neuron? This would have allowed its signal to be transmitted directly from one to the other, perhaps in the same way that two copper wires touching each other allow the flow of electricity to pass without any pause from one wire to the other.

• Or, were the neurons discontinuous, that is, spaced apart and not touching? If this were true, then the signal somehow needed to get across the gap between one neuron and the next. If that were true, how would it happen?

   Sir Charles Scott Sherrington (1857-1952) & the Discovery of the Synapse

Charles Scott Sherrington was an English neurologist, neuroscientist, professor at Oxford University, and winner (along with Edgar D. Adrian) of the Nobel Prize for Physiology and Medicine in 1932 for the work reported here.
 
Reflexes: automatic muscle responses to stimuli

Sensory neuron --> interneuron ("intrinsic") neuron --> motor neuron at level of the spinal cord = reflex arc

In experiments with dogs, Sherrington noted

• reflexes are slower than simple conduction along an axon would suggest.
    
• weak stimuli presented at different times or in different locations elicit a stronger response than a single strong stimulus does.
    
• excitation of one muscle set leads to relaxation in its opposing muscle set.    

From these observations, Sherrington concluded some of the most important qualities about synapses and transmission of messages within the nervous system.


Speed of Reflex & Delayed Transmission at the Synapse

• Sherrington stimulated dog's foot and the dog flexed its leg after a short delay. He found that the speed was about 15 meters/second. However, earlier research found speeds of 40 meters/second on individual sensory or motor axons. So, something must be delaying the speed.
  
  
• Sherrington reasoned that the delay in neural transmission in a reflex occurred because it took time for the signal to cross the from one neuron to the next. It takes about 0.5 mSec (1/2000 of a second) for a signal to cross. 
  

• Sherrington supported the argument of Ramon y Cajal that there was a small gap between neurons and called that gap the synapse (Greek "synapsis" = a juncture; from "syn-" [together] + "haptein" [to fasten]) 
     
  
• For his work, particularly regarding the function of the reflexes (which is further discussed below), he was awarded the Nobel Prize for Medicine & Physiology in 1932.

Summation: The effects of different kinds of stimulation on a neuron's tendency to fire

Two types: temporal and spatial

Temporal summation: repeated stimuli within a relatively short period of time can have a cumulative effect (see diagram below on left)
Sir John Eccles (1903-1997), a former student of Sherrington, showed temporal summation in single cells. Won the Nobel Prize in 1963 for his work on how inhibitory and excitatory processes occur at the synapse.   Spatial summation: stimuli occurring at different locations can have a cumulative effect. (See diagram on the far right.)

EPSPs and IPSPs: Effects at the Synapse

If one neuron stimulates another neuron, the first is called the presynaptic neuron and the second the postsynaptic neuron.

When the postsynaptic neuron receives a signal/message/firing across the synapse, various channels may open on the postsynaptic membrane and allow ions either to enter or to exit. This flow of ions causes a change in the electrical voltage on the inside of the postsynaptic neuron's membrane.

Excitatory Post-Synaptic Potential (EPSP)

• Usually happens when Na+ gates open up on the postsynaptic membrane and allow Na+ ions to enter.
• EPSPs make it more likely that the postsynaptic neuron will fire
  

Inhibitory Post-Synaptic Potential (IPSP)

Usually happens when K+ gates open up on the postsynaptic membrance and allow K+ ions to leave the neuron. Alternatively, channels for the chloride ion (Cl-) may open up and allow Cl- ions to enter the postsynaptic neuron. In either case, the inside of the postsynaptic membrane is, at least for a short while, more negative.

IPSPs make it less likely that the postsynaptic neuron will fire

Spontaneous Firing Rate of Individual Neurons

Our text also notes that many neurons have a spontaneous firing rate without even being stimulated. For example a neuron may fire spontaneously 10  to 20 times per second.

• Recent research (Brembs, 2021)  argues that the ultimate foundation for this phenomenon is the nature of the brain itself as a  dynamic organ which is constantly active even in the absence of stimulation.
  
  
• Uddin (2020) proposes that spontaneous neural firing may be related to how the brain functions predictively: "ongoing spontaneous cortical activity may represent a continuous prediction signal that interacts with incoming input to generate updated representations of the world" (p. 737). The same conclusion has been advanced by Pezzulo et al. (2021) who also add that the spontaneous activity of the brain in the absence of input is refining the models of the world which it uses to predict.
  
  
• Specific neurochemical factors which contribute to this spontaneous firing rate are quite complex (e.g., see Häusser et al., 2004, Mazzoni et al., 20007) and beyond what we can or need to review in this course.
  

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Chemical Events at the Synapse (pt. 1)

Otto Loewi (1873-1961) & Chemical Transmission at Synapses (1920)

In 1905, T. R. Elliott (Cambridge University, UK) had found that adrenaline (epinephrine) causes the heart to beat faster, relaxes the stomach muscles, dilates the pupils. These effects parallel stimulation of the sympathetic nervous system (SymNS) and, thus, led Elliott to wonder if the SymNS used a chemical like adrenaline to induce its effects.

One night in 1920, German physiologist, Otto Loewi, had an idea. He went to his laboratory and performed an experiment with a frog's heart. (see diagram). He used a frog's heart because it will continue beating on its own without stimulation if it is removed from the frog and placed in a liquid-filled beaker.

He stimulated the vagus nerve of the frog's heart repeatedly. The heart rate slowed down (this is an effect of the parasympathetic nervous system).

Then, he pumped the fluid from the beaker in which the stimulated heart was located into another beaker with a second frog's heart. That heart's beat also slowed down. He concluded that there was some chemical released by the heart after its vagus nerve had been stimulated which caused the second heart to slow down its beating. He did not know what that chemical was, but called it Vagusstoff (in English, "stuff from the vagus nerve"). Later on, the chemical was found to be acetylcholine, one of the neurotransmitters we will talk about below. He had stumbled upon a way in which, at the synapse, chemicals were used as transmission agents across the synaptic cleft.

Chemical Activity at the Synapse

References

Brembs, B. (2021). The brain as a dynamically active organ. Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2020.12.011

Häusser et al. (2004). The Beat Goes On: Spontaneous Firing in Mammalian Neuronal Microcircuits. Journal of Neuroscience, 24(42), 9215-9219.

Mazzoni A.,  et al. (2007) On the Dynamics of the Spontaneous Activity in Neuronal Networks. PLoS ONE, 2(5).

Pezzulo, G., Zorzi, M., & Corbetta, M. (2021). The secret life of predictive brains: what’s spontaneous activity for? Trends in Cognitive Sciences, 25(9), 730-743. https://doi.org/10.1016/j.tics.2021.05.007

Uddin, L. Q. (2020) Bring the noise: Reconceptualizing spontaneous neural activity. Trends in Cognitive Science, 24(9), 734-746. https://dx.doi.org//10.1016/j.tics.2020.06.003

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This first version of this page was posted January 30, 2005