03. Neurotransmitters and Neuromodulators

STUDY DESIGN DOT POINT:

The role of neurotransmitters in the transmission of neural information across a neural synapse to produce excitatory effects (as with glutamate) or inhibitory effects (as with gamma-amino butyric acid [GABA]) as compared to neuromodulators (such as dopamine and serotonin) that have a range of effects on brain activity

How Does The Nervous System Communicate?

Your nervous systems are constantly sending messages to and from your brain and body, but what format are these messages in?

Messages within a neuron take the form of electrical impulses that are transmitted from the dendrites through to the axon terminals of a neuron. BUT neurons are not physically connected, there are microscopic gaps between the axon terminal of one neuron and the dendrites of the next and the electrical impulse is unable to cross that "synaptic gap". This is where the chemical component of neural communication comes into play. Chemicals in the form of neurotransmitters are released at the axon terminal and "bind" with the post synaptic neuron to initiate further electrical communication along that neuron.

NEUROTRANSMITTERS

Neurotransmitters are extremely important for normal brain functioning, despite being small in size and affecting only one or two postsynaptic neurons. You will learn about neurotransmitters in this section of the lesson. Theory details Neurotransmitters are chemical molecules that have an effect on one or two postsynaptic neurons. This type of neurochemical enables rapid communication between two neurons across the neural synapse. There are two types of neurotransmitters:

• Excitatory neurotransmitters, which have an excitatory effect on the postsynaptic neuron.

• Inhibitory neurotransmitters, which have an inhibitory effect on the postsynaptic neuron.

Both inhibitory and excitatory neurotransmitters bind to their corresponding receptor sites on the dendrites of the postsynaptic neuron. The difference is the effect that they have on the postsynaptic neuron.

Excitatory Neurotransmitters increase the likelihood of the postsynaptic neuron carrying out its function (ie, the neuron continues to send the electrical neural impulse along the axon towards the axon terminals).

Inhibitory Neurotransmitters decrease the likelihood of the postsynaptic neuron carrying out its function (ie, the neuron does not continue to send the electrical neural impulse along the axon towards the axon terminals).

EXCITATORY NEUROTRANSMITTERS: GLUTAMATE

Glutamate is the main excitatory neurotransmitter in the CNS. This means that glutamate enhances information transmission by making postsynaptic neurons more likely to fire. It is the second most abundant neurotransmitter in the brain and is involved in most aspects of normal brain function, including learning, memory, perception, thinking and movement.

Due to its key role in learning and memory, Glutamate also has a significant impact on the neural structure of your brain insofar as it is vital in the formation of new synaptic connections and the strengthening of existing connections. This is known as synaptic plasticity and will be discussed in more detail later in this unit.

INHIBITORY NEUROTRANSMITTERS: GABA

Gamma-amino butyric acid (GABA) is the primary inhibitory neurotransmitter in the CNS. It works throughout the brain to make postsynaptic neurons less likely to fire (i.e. it ‘inhibits’ firing). One of its roles is to fine-tune neurotransmission in the brain and maintain neurotransmission at an optimal, or ‘best possible’, level.

Without the inhibitory effect of GABA, activation of postsynaptic neurons might get out of control. Their uncontrolled activation could spread throughout the brain, causing seizures similar to those of epilepsy and other problems. A lack of GABA (known as GABA dysfunction) can also result in some of the overactive thought processes that facilitate many anxiety disorders.

For effective daily functioning it is important that the nervous system maintains a healthy balance between both excitatory and inhibitory neurotransmitters

NEUROMODULATORS: DOPAMINE AND SEROTONIN

Neuromodulators are chemical molecules that have an effect on multiple postsynaptic neurons. This type of neurochemical modulates neural activity on a larger scale than neurotransmitters. This is because neuromodulators are released into multiple neural synapses and consequently affect multiple postsynaptic neurons, unlike neurotransmitters. Therefore, neuromodulators have widespread modulatory effects as they can influence large areas of brain tissue. Furthermore, the action of neuromodulators produces relatively long-lasting effects, as they modulate neural activity more slowly than neurotransmitters. However, like neurotransmitters, neuromodulators must bind to their specific receptor sites to have an effect on groups of postsynaptic neurons.

Neuromodulators can also modulate the effects of neurotransmitters by:

• changing the responsiveness of the receptor sites of a particular neurotransmitter, enhancing the excitatory or inhibitory effects of neurotransmitters.

• changing the neurotransmitter release pattern of the presynaptic neuron.

There are two neuromodulators that you will learn about in the following sections of the lesson: • dopamine

• serotonin

DOPAMINE

Dopamine is a neuromodulator known to have multiple functions depending on where in the brain it acts. For example, it has important roles in voluntary movements, the experience of pleasure, motivation, appetite, reward-based learning and memory. It has also been implicated in various mental conditions, including Parkinson’s disease, addiction and schizophrenia. Although primarily an excitatory neurotransmitter, dopamine can have either an excitatory effect at one location or an inhibitory effect at another, depending on the type of receptors that are present.

Dopamine's role in movement occurs primarily in the midbrain where dopamine producing neurons communicate with the primary motor cortex to enable smooth moto coordination. In the absence of sufficient dopamine in the midbrain, we are unable to regulate and coordinate motor activity. This is what we can see in Parkinsons Disease where the patient has difficulty maintaining posture, smooth movement and speech

Two other dopamine pathways overlap and are strongly associated with rewarding behaviour through the experience of pleasure. These pathways form what is commonly called the dopamine reward system. Behaviours that may be perceived as rewarding due to the release of dopamine include both healthy behaviours (such as eating when hungry and drinking when thirsty) and harmful behaviours that involve a loss of impulse control and have become addictive (such as gambling and video gaming).

SEROTONIN

Like dopamine, serotonin is a neuromodulator that has a wide range of functions, depending on where in the brain it acts. For example, it has important roles in mood, emotional processing, sleep onset, appetite and pain perception. As with dopamine, serotonin has been implicated in various mental conditions, including depression, anxiety disorders and sleep disorders. In addition, there are distinct serotonin producing areas and neural pathways along which seratonin travels to convey information to different brain areas and exert its influence.

nlike dopamine that can have both excitatory and inhibitory effects, serotonin only has inhibitory effects, so it does not stimulate brain activity. Its inhibitory effects can help counterbalance excessive excitatory effects of other neurotransmitters, as GABA does with glutamate. Serotonin is widely described as a mood stabaliser, with low levels associated with mood disorders such as depression and seasonal affective disorder. Depression involves an overemphasis of negative thoughts and emotions, including prolonged feelings of worthlessness and hopelessness, and a decrease in the reward produced by pleasurable experiences.

PODCAST LINK

NERVOUS SYSTEM 1.wav

LEARNING ACTIVITY 3.1.3a

Multiple Choice Questions

1. **Neurotransmitter Functions**:

- What is the primary role of glutamate in the central nervous system?

A) Inhibiting neuron firing

B) Enhancing neuron firing

C) Modulating mood and emotion

D) Regulating sleep cycles

2. **Inhibitory Neurotransmitters**:

- Which neurotransmitter is primarily responsible for inhibitory functions in the brain?

A) Dopamine

B) Serotonin

C) GABA

D) Glutamate

3. **Neuromodulators vs. Neurotransmitters**:

- How do neuromodulators differ from neurotransmitters?

A) Neuromodulators have immediate and localized effects, while neurotransmitters have broader and longer-lasting effects.

B) Neuromodulators can only influence motor functions, whereas neurotransmitters affect mood and cognition.

C) Neuromodulators have broader and longer-lasting effects, while neurotransmitters have immediate and localized effects.

D) There is no significant difference between neuromodulators and neurotransmitters.

4. **Role of Serotonin**:

- Which of the following is a primary function of serotonin?

A) Regulating reward and motivation

B) Enhancing excitatory synaptic transmission

C) Influencing mood, appetite, and sleep

D) Facilitating muscle contraction

5. **Clinical Implications of Neurotransmitter Imbalance**:

- An imbalance of which neurotransmitter is most commonly associated with depression?

A) Glutamate

B) GABA

C) Dopamine

D) Serotonin

6. **Dopamine Function**:

- Dopamine is primarily involved in:

A) Sleep regulation

B) Reward, motivation, and motor functions

C) Inhibiting neural activity

D) Enhancing learning and memory

3.1.3a ANSWERS

1. **Neurotransmitter Functions**:

- **Answer: B) Enhancing neuron firing**

- Explanation: Glutamate is the primary excitatory neurotransmitter in the central nervous system. It enhances neuron firing by promoting the influx of positive ions, which leads to depolarization of the neuron. The other options are incorrect because A) GABA is the neurotransmitter that inhibits neuron firing, C) and D) are functions more closely associated with neuromodulators like serotonin.

2. **Inhibitory Neurotransmitters**:

- **Answer: C) GABA**

- Explanation: GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the brain. It reduces neuronal excitability by facilitating the influx of negative ions into the neuron. A), B), and D) are incorrect as dopamine and serotonin are neuromodulators, and glutamate is an excitatory neurotransmitter.

3. **Neuromodulators vs. Neurotransmitters**:

- **Answer: C) Neuromodulators have broader and longer-lasting effects, while neurotransmitters have immediate and localized effects.**

- Explanation: Neuromodulators like dopamine and serotonin modulate the strength of synaptic transmission and can influence multiple neurons over a larger area, having longer-lasting effects. Neurotransmitters like glutamate and GABA have immediate and localized effects at specific synapses. A) reverses the roles, and B) and D) are incorrect characterizations.

4. **Role of Serotonin**:

- **Answer: C) Influencing mood, appetite, and sleep**

- Explanation: Serotonin plays a key role in regulating mood, appetite, and sleep. A) is incorrect as dopamine is more involved in reward and motivation, B) is incorrect as glutamate enhances excitatory transmission, and D) is not a primary function of serotonin.

5. **Clinical Implications of Neurotransmitter Imbalance**:

- **Answer: D) Serotonin**

- Explanation: Serotonin imbalance is most commonly associated with depression. It plays a significant role in mood regulation. A) Glutamate and B) GABA are more involved in excitatory and inhibitory neural activities, respectively, and C) Dopamine is more related to conditions like Parkinson's disease and schizophrenia.

6. **Dopamine Function**:

- **Answer: B) Reward, motivation, and motor functions**

- Explanation: Dopamine is primarily involved in the brain's reward system, motivation, and motor functions. A) is incorrect as serotonin is more involved in sleep regulation, C) is incorrect as GABA is the primary inhibitory neurotransmitter, and D) is incorrect as glutamate is more involved in learning and memory.

LEARNING ACTIVITY 3.1.3b

LEARNING ACTIVITY

1. **Basic Understanding of Neurotransmitters**:

- "Explain how neurotransmitters like glutamate and GABA function at a neural synapse. What distinguishes their roles in terms of excitatory and inhibitory effects on neural transmission?"

2. **Comparative Analysis of Neurotransmitters and Neuromodulators**:

- "Compare and contrast the roles of neurotransmitters such as glutamate and GABA with neuromodulators like dopamine and serotonin. How do their mechanisms of action and effects on brain activity differ?"

3. **Excitatory and Inhibitory Mechanisms**:

- "Discuss the importance of excitatory neurotransmitters like glutamate and inhibitory neurotransmitters like GABA in maintaining neural homeostasis. How do these neurotransmitters contribute to the overall functioning of the nervous system?"

4. **Role of Neuromodulators in Brain Activity**:

- "Describe the role of neuromodulators such as dopamine and serotonin in the brain. How do these substances influence mood, cognition, and behaviour differently from direct neurotransmitters?"

5. **Clinical Implications**:

- "Explore the clinical implications of imbalances in neurotransmitters and neuromodulators. How might an excess or deficiency of substances like glutamate, GABA, dopamine, or serotonin impact mental health and neurological disorders?"

3.1.3 b ANSWERS

1. **Basic Understanding of Neurotransmitters**:

- Glutamate and GABA are key neurotransmitters in the central nervous system. Glutamate is the primary excitatory neurotransmitter, enhancing the likelihood of a post synaptic action potential. GABA, on the other hand, is the main inhibitory neurotransmitter, reducing likelihood of post synaptic activation. This balance between excitation and inhibition by glutamate and GABA, respectively, is crucial for proper brain function and neural communication.

2. **Comparative Analysis of Neurotransmitters and Neuromodulators**:

- Neurotransmitters like glutamate and GABA have direct and immediate effects on neurons, typically at specific receptor sites, leading to quick changes in neuron activity. Neuromodulators like dopamine and serotonin, however, have a broader range of effects. They can modulate the strength of synaptic transmission, influence multiple neurons simultaneously, and have longer-lasting effects. While neurotransmitters are involved in fast synaptic transmission, neuromodulators are more about modulating the overall tone or state of neural circuits.

3. **Excitatory and Inhibitory Mechanisms**:

- Excitatory neurotransmitters like glutamate are essential for stimulating neural activity, promoting learning, memory, and neural plasticity. Inhibitory neurotransmitters like GABA provide a counterbalance, preventing overexcitation and potential neural damage. This balance is vital for neural homeostasis, ensuring that neural circuits do not become overactive or underactive, which can lead to neurological or mental health disorders.

4. **Role of Neuromodulators in Brain Activity**:

- Neuromodulators such as dopamine and serotonin play significant roles in regulating mood, cognition, and behaviour. Dopamine is heavily involved in reward, motivation, and motor functions, while serotonin influences mood, appetite, and sleep. Unlike direct neurotransmitters that have immediate and localized effects, neuromodulators can diffuse over larger brain areas, affecting multiple neural pathways and thus influencing a broader range of brain functions.

5. **Clinical Implications**:

- Imbalances in neurotransmitters and neuromodulators can lead to various mental health and neurological disorders. For example, excess glutamate can cause excitotoxicity, leading to conditions like epilepsy, while GABA deficiency can result in anxiety or seizures. Similarly, dopamine dysregulation is associated with Parkinson's disease and schizophrenia, and serotonin imbalances are linked to depression and anxiety disorders. Understanding these imbalances is crucial for developing effective treatments.

Past Exam Question

Past Exam Question Answer

Please note that as this question is from a previous study design, you are not expected to know the role of adrenaline in this process. Glutamate is the accepted neurotransmitter in this study design.

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