Synapses (lec2)

Synaptic Transmission Overview

  • Types of Synapses:

    • Electrical Synapse (Gap Junction): Characterized by direct current flow between cells through gap junction channels formed by connexons. This allows for very rapid, bidirectional transmission and synchronization of neuronal activity, but offers limited opportunities for modulation of the signal. 

      • Not common in nervous system, but prevalent in cardiac muscle as it synchronizes a lot of cells at one time - no decision making process, if pre cell has AP then post cell will also 

    • Chemical Synapse: Involves the release of neurotransmitters from the presynaptic neuron into a synaptic cleft, which then bind to receptors on the postsynaptic neuron. This type of synapse is slower than electrical synapses but allows for much greater flexibility, amplification, and modulation of the signal.

      • common in the nervous system - if there is an AP in pre cell we are not guaranteed one in post cell 

  • Neurons Structure:

    • Presynaptic neuron: The neuron transmitting the signal. It contains synaptic vesicles filled with neurotransmitters, clustered at active zones near the presynaptic membrane, ready for release.

    • Postsynaptic neuron: The neuron receiving the signal. Its membrane possesses specialized receptors (ligand-gated ion channels or G-protein coupled receptors) that specifically bind neurotransmitters, triggering a response.

    • Axon hillock: The critical integration zone at the beginning of the axon where all incoming excitatory and inhibitory signals (EPSPs and IPSPs) are summed. If the summed potential reaches the threshold, an action potential is generated.

    • Dendrites: Branching extensions of the neuron that receive synaptic input from other neurons. Many dendrites are covered with dendritic spines, which are small protrusions that increase the surface area for synaptic contact and can dynamically change their shape and size, contributing to synaptic plasticity.

  • Action Potentials:

    • Triggered when an electrical signal (depolarization) reaches the presynaptic terminal, specifically initiating the opening of voltage-gated calcium (Ca2+Ca^{2+}) channels.

    • Calcium ions influx leads to neurotransmitter release: The entry of Ca2+Ca^{2+} into the presynaptic terminal is crucial. It triggers a cascade of events involving SNARE proteins, leading to the fusion of synaptic vesicles with the presynaptic membrane and the subsequent exocytosis (release) of neurotransmitters into the synaptic cleft.

  • Postsynaptic Potentials:

    • EPSP (Excitatory PostSynaptic Potential): A transient depolarization of the postsynaptic membrane, typically caused by the influx of positive ions, most commonly sodium (Na+Na^{+}) ions. EPSPs bring the membrane potential closer to the threshold for generating an action potential and are therefore excitatory.

    • IPSP (Inhibitory PostSynaptic Potential): A transient hyperpolarization or stabilization of the postsynaptic membrane potential, typically caused by the influx of chloride (Cl−Cl^{-}) ions or efflux of potassium (K+K^{+}) ions. IPSPs make the membrane potential more negative or keep it from depolarizing, moving it further away from the threshold, thus inhibiting action potential generation.

    • Both EPSPs and IPSPs are graded potentials, meaning their amplitude is proportional to the strength of the synaptic input, and they summate spatially and temporally to determine the overall effect on the postsynaptic neuron.

  • Neurotransmitter Types:

    • Amino Acids: Building blocks of proteins and most abundant. Fast-acting, typically mediate rapid synaptic transmission.

      • Glutamate: The primary excitatory neurotransmitter in the central nervous system (CNS).

      • Glycine: An inhibitory neurotransmitter, particularly in the spinal cord and brainstem.

      • GABA (Gamma-aminobutyric acid): The primary inhibitory neurotransmitter in the brain.

    • Amines: More complex than AA. Often serve as neuromodulators, influencing broad brain states.

      • Acetylcholine: Involved in muscle contraction (neuromuscular junction), autonomic nervous system, and CNS functions like learning and memory.

      • Dopamine, Norepinephrine, Serotonin, Epinephrine: Catecholamines and indolamines involved in mood, reward, attention, sleep, and arousal.

    • Peptides: Smaller protein chains (larger molecules). Often co-released with smaller neurotransmitters, typically have slower and longer-lasting modulatory effects.

      • Neuropeptide Y, Substance P, Enkephalins: Involved in diverse functions such as pain perception, stress responses, appetite, and emotional states.

  • Receptor Diversity:

    • Each neurotransmitter can activate multiple receptor subtypes, leading to varied postsynaptic effects (e.g., Glutamate: NMDA, AMPA, Kainate receptors are ionotropic, while metabotropic glutamate receptors are GPCRs).

    • Receptor determines the action, not the transmitter: The effect of a neurotransmitter (excitatory or inhibitory) depends entirely on the specific type of receptor it binds to on the postsynaptic membrane and the ion channels or signaling pathways associated with that receptor.

  • G-protein Coupled Receptors:

    • Involved in modulating ion channels and enzymes like adenylyl cyclase: When a neurotransmitter binds to a GPCR, it activates an intracellular G-protein. The activated G-protein then dissociates and interacts with various effector proteins, such as ion channels (direct modulation) or enzymes.

    • Activate second messengers leading to cellular responses: Enzymes like adenylyl cyclase produce second messengers (e.g., cyclic AMP, or cAMP), which can then initiate a cascade of intracellular events, including protein phosphorylation, changes in gene expression, and ultimately, diverse and often long-lasting cellular responses.

  • Modulation Mechanisms:

    • Presynaptic inhibition modifies transmitter release: Often occurs through axo-axonic synapses, where one neuron synapses onto the axon terminal of another, typically reducing the amount of Ca2+Ca^{2+} influx into the presynaptic terminal, thereby decreasing neurotransmitter release.

    • Modulation of receptor activity through G-proteins affects synaptic strength: GPCRs can directly alter ion channel conductance, change the sensitivity of postsynaptic receptors, or modify the release probability of neurotransmitters from the presynaptic terminal.

      • modulation: may want to turn up some behaviours when awake/asleep and turn down some when awake/asleep - modulation is used for prolonged chnages in behavious

    • Can alter gene expression and cell properties leading to long-term changes: This is a fundamental mechanism underlying synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), which involve changes in the number or efficacy of receptors, synthesis of new proteins, or even structural alterations in synapses, contributing to learning and memory.

  • Communication Types: both occur by neurotransmitters being released

    • Point-to-Point: Characterized by rapid, precise, and direct synaptic transmission typically involving ionotropic receptors and rapid EPSPs/IPSPs. This type of communication is essential for immediate, localized responses such as sensory processing, reflexes, and motor commands (tendon tap reflex & sensory info transmission from eyes to cortex) 

    • Diffuse Modulation: Involves slower, more widespread, and prolonged effects, often through G-protein coupled receptors and second messenger systems. Neuromodulators released in this manner can affect large networks of neurons, altering overall excitability, mood, attention, sleep-wake cycles, and general brain states over a longer duration (about coordinating systems within CNS)