Synaptic transmission is the key to neural communication. Neurons release chemicals called neurotransmitters that bind to receptors on other cells, triggering changes in their activity. This process allows information to flow through the nervous system, shaping our thoughts, feelings, and behaviors.

Understanding synaptic transmission is crucial for grasping how the brain works. Different neurotransmitters and receptors play specific roles in various brain functions, from mood regulation to memory formation. This knowledge forms the basis for many psychiatric medications and treatments.

Synaptic Transmission at Chemical Synapses

Process of Synaptic Transmission

• Synaptic transmission enables communication between neurons or neurons and other cells (muscle or gland cells) at specialized junctions called synapses
• In chemical synapses, the presynaptic neuron releases neurotransmitters into the synaptic cleft which bind to specific receptors on the postsynaptic cell membrane
• Synaptic transmission involves several steps:
  1. Synthesis and storage of neurotransmitters in synaptic vesicles
  2. Release of neurotransmitters into the synaptic cleft by exocytosis
  3. Binding of neurotransmitters to postsynaptic receptors
  4. Termination of the signal by neurotransmitter reuptake or enzymatic degradation
• Action potential arrival at the presynaptic terminal opens voltage-gated calcium channels allowing calcium ions to enter the presynaptic neuron triggering neurotransmitter release

Factors Influencing Neurotransmitter Release and Duration

• Amount of neurotransmitter released and duration of action depend on several factors:
  • Frequency and intensity of presynaptic activity
  • Availability of neurotransmitters
  • Efficiency of neurotransmitter reuptake or degradation
• Higher frequency and intensity of presynaptic activity generally lead to greater neurotransmitter release (temporal summation)
• Neurotransmitter availability is influenced by the rate of synthesis, storage, and release from synaptic vesicles
• Efficient reuptake or degradation of neurotransmitters helps terminate the signal and prevents excessive postsynaptic stimulation (serotonin reuptake inhibitors, acetylcholinesterase)

Neurotransmitter Types and Functions

Amino Acid Neurotransmitters

• Amino acid neurotransmitters include:
  • Glutamate: main excitatory neurotransmitter in the CNS
  • GABA: main inhibitory neurotransmitter in the CNS
  • Glycine: inhibitory neurotransmitter in the spinal cord and brainstem
• Glutamate is involved in learning, memory, and synaptic plasticity (long-term potentiation)
• GABA plays a role in regulating anxiety, sleep, and muscle tone (benzodiazepines enhance GABA function)

Monoamine and Peptide Neurotransmitters

• Monoamine neurotransmitters include:
  • Catecholamines: dopamine, norepinephrine, and epinephrine
  • Indolamines: serotonin and melatonin
• Monoamines are involved in various functions such as mood, attention, sleep, and autonomic regulation (antidepressants, stimulants)
• Peptide neurotransmitters include endorphins, enkephalins, and substance P involved in pain modulation, emotion, and other functions (opioid analgesics)

Other Neurotransmitters

• Acetylcholine is involved in muscle contraction, memory, and attention (nicotinic and muscarinic receptors)
• Endocannabinoids are involved in pain modulation and appetite regulation (cannabis)
• Nitric oxide is a gaseous neurotransmitter involved in vasodilation and synaptic plasticity (nitroglycerin)
• ATP and adenosine are purinergic neurotransmitters involved in neuron-glia communication and sleep regulation (caffeine)

Receptors in Neurotransmitter Signaling

Types of Neurotransmitter Receptors

• Neurotransmitter receptors are proteins in the postsynaptic cell membrane that specifically bind to neurotransmitters released by the presynaptic neuron
• Two main types of neurotransmitter receptors:
  1. Ionotropic receptors: ligand-gated ion channels that directly open or close upon binding to neurotransmitters leading to rapid changes in postsynaptic membrane potential (nicotinic acetylcholine receptors, AMPA receptors)
  2. Metabotropic receptors: G protein-coupled receptors that indirectly modulate ion channels or other cellular processes through intracellular signaling cascades leading to slower and longer-lasting effects (muscarinic acetylcholine receptors, mGluRs)

Receptor Function and Regulation

• Type, density, and distribution of neurotransmitter receptors on the postsynaptic cell determine the nature and strength of the postsynaptic response to neurotransmitter release
• Receptor regulation modulates synaptic transmission and plasticity:
  • Desensitization: reduced response to repeated or prolonged exposure to neurotransmitters
  • Sensitization: enhanced response to repeated or prolonged exposure to neurotransmitters
  • Receptor trafficking: changes in the number or location of receptors on the postsynaptic membrane (AMPA receptor insertion during LTP)
• Receptor agonists and antagonists can modulate neurotransmitter signaling (benzodiazepines as GABA receptor agonists, antipsychotics as dopamine receptor antagonists)

Excitatory vs Inhibitory Postsynaptic Potentials

Excitatory Postsynaptic Potentials (EPSPs)

• EPSPs are depolarizing events that bring the postsynaptic cell's membrane potential closer to the threshold for generating an action potential increasing the likelihood of the postsynaptic neuron firing
• EPSPs are typically generated by the opening of cation channels (sodium or calcium) in response to the binding of excitatory neurotransmitters (glutamate) to ionotropic receptors (AMPA, NMDA)
• Summation of multiple EPSPs can lead to the generation of an action potential in the postsynaptic neuron (spatial and temporal summation)

Inhibitory Postsynaptic Potentials (IPSPs)

• IPSPs are hyperpolarizing events that move the postsynaptic cell's membrane potential further away from the threshold for generating an action potential decreasing the likelihood of the postsynaptic neuron firing
• IPSPs are typically generated by the opening of anion channels (chloride) or the closing of cation channels in response to the binding of inhibitory neurotransmitters (GABA, glycine) to ionotropic receptors (GABA_A, glycine receptors)
• IPSPs can shunt excitatory inputs and prevent the generation of an action potential in the postsynaptic neuron (feedforward and feedback inhibition)

Integration of EPSPs and IPSPs

• The net effect of synaptic transmission on the postsynaptic cell depends on the integration of multiple EPSPs and IPSPs over time and space
• Intrinsic properties of the postsynaptic neuron (resting membrane potential, input resistance, threshold potential) influence the integration of synaptic inputs
• Balance between excitation and inhibition is crucial for proper neural circuit function and plasticity (E/I balance in cortical circuits)