1. Topic A.5 - Neuropharmacology
Essential idea: Communication between neurons can be altered through the manipulation of the release and reception of chemical messengers.

2. Some neurotransmitters excite nerve impulses in postsynaptic neurons and others inhibit them.
Remember – A synapse is a place where neuron’s interact and neurotransmitters (NTs) are released via exocytosis and left to diffuse across the synapse, with the ultimate goal of binding to the postsynaptic cell.
All neurotransmitters fall into one of two categories: excitatory or inhibitory
This is based on their effect on the post-synaptic neurons, which can either be to depolarize the neuron (leading towards an action potential), or to hyperpolarize the neuron (leading away from an action potential).

3. Nerve impulses are initiated or inhibited in post-synaptic neurons as a result of summation of all excitatory and inhibitory neurotransmitters received from presynaptic neurons.
In reality, very few synapses exist in a vacuum, almost all postsynaptic neurons have more than one presynaptic neuron that is synapsing with it.
(Often there can be hundreds or even thousands of presynaptic neurons synapsing with a single post-synaptic cell)
Of the presynaptic neurons, some will be excitatory, and some will be inhibitory, and these can be releasing NTs simultaneously, and each impact the potential of the post-synaptic neuron.
This creates an additive effect, in which it is about the balance between excitatory (EPSPs) and inhibitory (IPSPs) events that determine whether an action potential is created or not.
The combined effect of IPSPs and EPSPs is called summation.

4. Nerve impulses are initiated or inhibited in post-synaptic neurons as a result of summation of all excitatory and inhibitory neurotransmitters received from presynaptic neurons.
If the total sum of incoming signals is excitatory, then an action potential is fired, whereas if the sum of the incoming potentials is inhibitory, then a signal is not carried.
Summation can occur in two major ways – Temporally or Spatially.
Identify the types of summation shown in this diagram.
Temporal summation is based on the rate of signals, and a quick series of action potentials will yield an effect on the post-synaptic neuron
Spatial summation is where more than one neuron acts simultaneously to initiate an effect ton the post-synaptic neuron.

5. Nerve impulses are initiated or inhibited in post-synaptic neurons as a result of summation of all excitatory and inhibitory neurotransmitters received from presynaptic neurons.
Practice Problem -

6. Nerve impulses are initiated or inhibited in post-synaptic neurons as a result of summation of all excitatory and inhibitory neurotransmitters received from presynaptic neurons.
Practice Problem -

7. Many different slow-acting neurotransmitters modulate fast synaptic transmission in the brain.
There are both fast acting and slow acting neurotransmitters in the brain.
Fast NT examples: GABA (IN), Glutamate (EX)
Slow NT examples:
Dopamine (BOTH)
Serotonin (IN)
Slow acting NTs (Often called neuromodulators) act on a secondary messenger protein that open channels for ions – this results in a longer term effect on the neuron, but slower response time
Fast acting NTs can have an effect on the post-synaptic cell within 1 ms of release, but have a short term effect.

8. Memory and learning involve changes in neurons caused by slow-acting neurotransmitters.
Slow acting neurotransmitters have a role in memory and learning, mostly through the release of secondary messengers.
These messengers can actually modify the number of receptors in the membrane or they can modify the efficacy of the receptors to increase the rate of ion movement into the neuron when the NT binds
Biological Perspective
Learning – Modifications of the number of protein channels, the size and shape of the neuron, and the number of NTs in the synapse are biological modifications that contribute to learning.
These secondary messengers can persist for days, which causes Long Term Potentiation (LTP)
Learning
Memory
LTP is essential for the synaptic plasticity that is necessary for memory and learning, primarily shown by the formation of new synapses in the hippocampus
Memory - LTP makes neurons begin to fire easier and easier, which lets the cells initiate action potentials more rapidly, which we know as memory.

9. Memory and learning involve changes in neurons caused by slow-acting neurotransmitters.
Notice the structural changes made to the neuron through constant stimulation.
1. Number of channels on postsynaptic cell are increased
2. Size of the synapse and shape of synapse are changed to allow more connections.
3. The number of NTs that are made is changed to allow for more signals to be sent.

10. Psychoactive drugs affect the brain by either increasing or decreasing postsynaptic transmission.
Drugs that increase neurotransmission levels are stimulants and increase psychomotor arousal and alertness
Drugs that decrease neurotransmission levels are depressants and slow down brain activities and relax muscles
Stimulant drugs mimic the stimulation provided by the sympathetic nervous system (i.e. 'fight or flight’ responses)
Examples of stimulants include caffeine, cocaine, amphetamines, ecstasy (MDMA) and nicotine
Depressants reduce stimulation of the central nervous system and may induce sleep (sedatives)
Examples of sedatives include benzodiazepines, barbiturates, alcohol and THC (cannabis)

11. GA - Loss of Consciousness, due to brain transmission being affected.
Anesthetics act by interfering with neural transmission between areas of sensory perception and the CNS.
Local anesthesia works to prevent sodium from entering the postsynaptic cell in a small region of the body, thereby preventing action potentials.
Ex. Epidural
GA - Loss of Consciousness, due to brain transmission being affected.
General Anesthesia will work to block synapses from initiating an action potential for the whole body, either by blocking postsynaptic cell, or by preventing presynaptic cell from releasing NTs.
Ex. Barbiturates or Benzodiazepine
LA – NO Loss of Consciousness, due to brain transmission being unaffected.

12. Anesthetics act by interfering with neural transmission between areas of sensory perception and the CNS. Naturally occurring endorphins can act as an anesthetic.
This is a big part of how athletes can continue to play in a sports game, even after being seriously injured.
This is also the reason that endorphins feel so good, as they target the same opiate receptors that generate euphoria.

13. Addiction can be affected by genetic predisposition, social environment and dopamine secretion.
Addiction is a dependence on a substance or an activity which results in repeated and compulsive use
This repeated and compulsive use conditions the body in a reflexive and operant manner to develop patterns that are outside the norm, and lead back to the substance or addiction
TED – Addiction Talk
Addictions, when broken, leave the body with withdrawal symptoms (mostly mental, sometimes physical) that continue to affect the body.
Ages that experience withdrawal symptoms per year

14. Genetic components of addiction:
Addiction can be affected by genetic predisposition, social environment and dopamine secretion.
Genetic components of addiction:
Specific genes might influence the rate of drug metabolism or intensity of drug effect (i.e. dopamine secretion)
Genetic factors may also contribute to personality types that are more inclined towards addictive behaviors
The genetic predisposition for a particular addiction may be determined by polygenic inheritance
Dopamine Secretion
Dopamine is a neurotransmitter released within the limbic system in response to reward (activates pleasure pathways)
Certain drugs (e.g. cocaine, heroin) and particular activities (e.g. sex, gambling) enhance dopamine activity
Long-term substance abuse will lead to the down-regulation of dopamine receptors, requiring higher doses to achieve effect
Consequently, addicts must continue to repeat the addictive activity in order to achieve a diminishing level of reward

15. Addiction can be affected by genetic predisposition, social environment and dopamine secretion.
Individuals raised in environments with prevalent substance abuse are at higher risk of addiction (peer pressure risks)
Individuals treated with neglect (child abuse) or suffering significant personal trauma are at a higher risk of addiction
Certain cultures have a higher incidence of addictions (may reflect demographic influences or marketing forces)
Low socioeconomic status (i.e. poverty) may increase the likelihood of addiction (poor education / lack of support networks)
Watch this great Kurzgesagt on addiction!

16. Neuropharmacology Inquiry – Mouse Party!
The goal – To understand the way drugs work in the brain, and how they are able to manipulate the neurotransmitters in your brain to change the way you think.
General Info: Classify all drugs as either stimulants, psychoactive or depressants.
Classify each of the responses as an inhibitory or stimulatory response on the postsynaptic cell
Identify the specific effects of at least two stimulants and two depressants on the nervous system
Determine the factors that feed into addiction – genetic, environmental, dopamine secretion
Evaluate endorphins as painkillers.
Evaluate the effect of MDMA on dopamine and serotonin metabolism in the brain.
Click the mice for the link to the website.
Produce a chart on a sheet of paper with the answers to each of these questions on it.