2.2 Major neurotransmitters and their roles

Neurotransmitters are the brain's chemical messengers, essential for communication between neurons. This section explores major neurotransmitters like glutamate, GABA, dopamine, and serotonin, detailing their roles in brain function.

Understanding these neurotransmitters is crucial for grasping how the brain processes information and regulates behavior. We'll examine how imbalances in these chemicals can lead to various neurological and psychiatric disorders, connecting to broader concepts in neuroanatomy.

Amino Acid Neurotransmitters

Excitatory and Inhibitory Neurotransmitters

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• Glutamate functions as the primary excitatory neurotransmitter in the central nervous system
  • Plays a crucial role in learning and memory formation
  • Involved in synaptic plasticity and long-term potentiation
  • Excessive glutamate can lead to excitotoxicity (neuronal damage or death)
• GABA (gamma-aminobutyric acid) serves as the main inhibitory neurotransmitter in the brain
  • Reduces neuronal excitability throughout the nervous system
  • Contributes to the regulation of anxiety, sleep, and muscle tone
  • Imbalances in GABA levels associated with various neurological disorders (epilepsy, anxiety)
• Excitatory neurotransmitters increase the likelihood of neuronal firing
  • Depolarize the postsynaptic membrane
  • Other examples include aspartate and glycine (in certain contexts)
• Inhibitory neurotransmitters decrease the likelihood of neuronal firing
  • Hyperpolarize the postsynaptic membrane
  • Other examples include glycine (in the spinal cord and brainstem)

Neurotransmitter Balance and Signaling

• Balance between excitatory and inhibitory neurotransmission maintains proper brain function
  • Disruptions in this balance linked to various neurological and psychiatric disorders
• Glutamate and GABA work together to regulate neuronal activity
  • Glutamate excites neurons, while GABA inhibits them
  • This interplay crucial for information processing and neural circuit function
• Amino acid neurotransmitters synthesized from common metabolic precursors
  • Glutamate derived from glutamine or α-ketoglutarate
  • GABA synthesized from glutamate via the enzyme glutamate decarboxylase
• Signaling mechanisms involve specific receptors for each neurotransmitter
  • Glutamate receptors include AMPA, NMDA, and kainate receptors
  • GABA receptors include GABA-A (ionotropic) and GABA-B (metabotropic) receptors

Monoamine Neurotransmitters

Dopamine and Its Functions

• Dopamine plays a crucial role in reward-motivated behavior and motor control
  • Involved in the brain's reward system, reinforcing pleasurable activities
  • Regulates movement by modulating activity in the basal ganglia
  • Imbalances in dopamine associated with disorders like Parkinson's disease and schizophrenia
• Dopamine synthesized from the amino acid tyrosine
  • Conversion of tyrosine to L-DOPA, then to dopamine
  • Stored in synaptic vesicles and released upon neuronal firing
• Dopaminergic pathways in the brain include
  • Mesolimbic pathway (reward and motivation)
  • Mesocortical pathway (cognitive control)
  • Nigrostriatal pathway (motor control)
• Dopamine receptors classified into two main families
  • D1-like receptors (D1 and D5)
  • D2-like receptors (D2, D3, and D4)

Serotonin and Norepinephrine: Mood and Arousal Regulators

• Serotonin influences mood, sleep, appetite, and social behavior
  • Often referred to as the "feel-good" neurotransmitter
  • Imbalances linked to depression, anxiety, and obsessive-compulsive disorder
  • Synthesized from the amino acid tryptophan
• Norepinephrine functions in arousal, attention, and stress response
  • Increases heart rate, blood pressure, and blood glucose levels
  • Plays a role in the fight-or-flight response
  • Synthesized from dopamine via the enzyme dopamine β-hydroxylase
• Both serotonin and norepinephrine targeted by various antidepressant medications
  • Selective Serotonin Reuptake Inhibitors (SSRIs) increase serotonin availability
  • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) affect both neurotransmitters
• Monoamine oxidase (MAO) enzyme responsible for breaking down these neurotransmitters
  • MAO inhibitors used as antidepressants by preventing neurotransmitter breakdown

Other Neurotransmitters and Neuromodulators

Acetylcholine: The Neuromuscular Messenger

• Acetylcholine functions in both the central and peripheral nervous systems
  • Acts as a neurotransmitter at neuromuscular junctions, facilitating muscle contraction
  • Plays a crucial role in attention, arousal, and memory in the brain
  • Synthesized from choline and acetyl-CoA by the enzyme choline acetyltransferase
• Two main types of acetylcholine receptors
  • Nicotinic receptors (ionotropic) found at neuromuscular junctions and in the brain
  • Muscarinic receptors (metabotropic) primarily in the central nervous system and smooth muscle
• Acetylcholinesterase rapidly breaks down acetylcholine in the synaptic cleft
  • Ensures precise temporal control of signaling
  • Acetylcholinesterase inhibitors used to treat Alzheimer's disease
• Dysfunction in cholinergic signaling associated with various neurological disorders
  • Alzheimer's disease characterized by loss of cholinergic neurons
  • Myasthenia gravis involves autoimmune attack on acetylcholine receptors

Endorphins and Neuromodulators: Fine-tuning Neural Activity

• Endorphins act as natural pain relievers and mood enhancers
  • Produced by the body in response to stress, pain, or intense exercise
  • Bind to opioid receptors, reducing pain perception and inducing feelings of euphoria
  • Involved in the "runner's high" experienced during prolonged exercise
• Neuromodulators alter the effects of other neurotransmitters
  • Can enhance or diminish the strength of synaptic transmission
  • Often act over longer time scales compared to classical neurotransmitters
• Examples of neuromodulators include
  • Neuropeptides (substance P, neuropeptide Y)
  • Endocannabinoids (anandamide, 2-arachidonoylglycerol)
  • Nitric oxide, a gaseous neuromodulator
• Neuromodulators often co-released with classical neurotransmitters
  • Can fine-tune synaptic transmission and neuronal excitability
  • Play important roles in regulating mood, appetite, and pain perception