Neuroscience Chapter on Synaptic Integration

Quantal Analysis

• Quantal analysis determines the number of vesicles that release during neurotransmission
• The neuromuscular junction has around 200 synaptic vesicles and releases an EPSP of 40mV or more
• CNS synapses have only a single vesicle releasing an EPSP of a few tenths of a millivolt

Principles of Synaptic Integration

• EPSP Summation is the process by which EPSPs are added together to produce a significant postsynaptic depolarization
• Spatial summation occurs when EPSPs are generated simultaneously at different synapses
• Temporal summation occurs when EPSPs are generated at the same synapse in rapid succession (within 1-15 milliseconds of each other)
• This allows neurons to perform complex computations

Contribution of Dendritic Properties to Synaptic Integration

• Dendrites can be modeled as straight cables
• Membrane depolarization decreases exponentially with increasing distance from the synapse
• Dendritic length constant (λ) is a measure of how far depolarization can spread down a dendrite
• λ is determined by the internal resistance (ri) and the membrane resistance (rm) of the dendrite
• A longer length constant means that EPSPs generated at distant synapses are more likely to depolarize the membrane at the axon hillock
• λ increases as membrane resistance increases and decreases as internal resistance increases
• A wide dendrite with fewer open membrane channels will have a longer length constant

Synaptic Excitation

• Dendrites have a small number of voltage-gated sodium, calcium, and potassium channels
• These channels can act as amplifiers but are not enough to generate an action potential

Synaptic Inhibition

• Synaptic inhibition decreases the membrane potential away from the action potential threshold
• Most inhibitory synapses are permeable to chloride ions, allowing chloride to flow inward toward its equilibrium potential (-65mV)
• IPSPs and shunting inhibition exert a powerful control over neuron output

Basic Steps of Chemical Synaptic Transmission

• Synthesis of neurotransmitter
• Loading neurotransmitter into synaptic vesicles
• Fusion of vesicles to the presynaptic terminal
• Release of neurotransmitter into the synaptic cleft
• Binding of neurotransmitter to postsynaptic receptors
• Elicitation of a biochemical or electrical response in the postsynaptic cell
• Removal of neurotransmitter from the synaptic cleft

Neurotransmitters

• Amino acids: Glutamate, glycine, GABA
• Amines: Dopamine, acetylcholine, histamine
• Peptides: short amino acid chains (i.e., proteins) stored in and released from secretory granules (somatostatin, thyrotropin-releasing hormone, neuropeptide Y)

Neurotransmitter Release: Exocytosis

• Exocytosis is the process by which vesicles release their contents
• The arrival of an action potential at the terminal stimulates the process of exocytosis through an increase in intracellular calcium concentration ([Ca2+]i) via voltage-gated calcium channels
• SNARE proteins change conformation and facilitate vesicle membrane incorporation into the presynaptic membrane
• This leads to neurotransmitter release and vesicle membrane recovery via endocytosis

Calcium Channels

• Calcium channels are composed of a single gene product
• They have a selectivity filter that distinguishes them from sodium channels
• Several different types of calcium channels exist:
  • N- and P-type: responsible for synaptic transmission in most neurons
  • T-type ("transient"): activated by small depolarizations and influence the likelihood of spiking
  • L-type: involved in muscle contraction and synaptic transmission in some sensory cells
  • IP3 receptor: releases Ca2+ from the endoplasmic reticulum and plays a role in intracellular signaling

Neurotransmitter Receptors

• Ionotropic receptors:
  • Transmitter-gated ion channels comprised of four or five subunits that join to form a pore
  • Closed in the absence of a ligand
  • Binding of a ligand (neurotransmitter) leads to a conformational change that opens the pore
  • Less selective for ions than voltage-gated channels
  • "Faster" pathway
• Metabotropic receptors:
  • G-protein-coupled receptors
  • Slower and longer-lasting signal
  • Three steps:
    • Neurotransmitter binds to the receptor
    • Receptor activates a G protein
    • G protein activates an effector protein (ion channel or enzyme that produces a secondary messenger)

Excitatory and Inhibitory Postsynaptic Potentials (EPSPs and IPSPs)

• EPSP: Transient postsynaptic membrane depolarization caused by the presynaptic release of neurotransmitter
• IPSP: Transient hyperpolarization of the postsynaptic membrane potential caused by the presynaptic release of neurotransmitter

Neurotransmitter Recovery and Degradation

• Diffusion: neurotransmitter diffuses away from the synapse
• Reuptake: neurotransmitter re-enters the presynaptic axon terminal (mediated by clathrin protein)
• Enzymatic destruction: neurotransmitter is broken down inside the terminal cytosol or the synaptic cleft
• Desensitization: e.g., acetylcholinesterase (AChE) cleaves acetylcholine (ACh) into inactive state

Neuropharmacology

• Drugs can affect the nervous system by interacting with neurotransmitter receptors
• Receptor antagonists: inhibitors of neurotransmitter receptors (e.g., curare blocks muscle contraction at acetylcholine receptors)
• Receptor agonists: mimic the actions of naturally occurring neurotransmitters (e.g., nicotine activates skeletal muscle and CNS acetylcholine receptors)
• Defective neurotransmission is the underlying cause of neurological and psychiatric disorders

Synaptic Integration

• Synaptic integration is the process by which multiple synaptic potentials combine within a single postsynaptic neuron

Quantal Analysis of EPSPs

• Bernard Katz (1952) discovered spontaneous changes in muscle cell membrane potential in the absence of stimulation
• These changes were called miniature end plate potentials (MEPPs) and had the same shape as EPSPs but were much smaller (~1mV)
• Synaptic vesicles are the elementary units of synaptic transmission
• A quantum is an indivisible unit representing the number of transmitter molecules in a single vesicle and the number of postsynaptic receptors available at the synapse

Introduction to Synaptic Transmission

• Synaptic transmission refers to the transfer of information at a synapse
• Played a role in all aspects of nervous system function
• Charles Sherrington (1897) coined the term "synapse"
• Synapses can be chemical or electrical

Types of Synapses

• Electrical synapses:
  • Allow direct transfer of ionic current from one cell to the next
  • Composed of gap junctions, which are channels formed by two connexons (each made of six connexins)
  • Cells are said to be electrically coupled, with ions flowing directly from the cytoplasm of one cell to the cytoplasm of the other
  • The pore diameter is around 1-2 nm, allowing ions and small organic molecules to pass through
  • Transmission is fast and bidirectional
  • Leads to postsynaptic potentials (PSPs)
  • Found in the brain stem (breathing), interneurons in the cerebral cortex, thalamus, cerebellum, and hypothalamus (vasopressin and oxytocin)
  • Important during early development
• Chemical synapses:
  • Contain a synaptic cleft (20-50 nm wide) filled with fibrous extracellular proteins
  • Use synaptic vesicles and secretory granules (dense-core vesicles)
  • Have membrane differentiations called active zones (presynaptic) and postsynaptic density (postsynaptic)

CNS Synapses

• Axodendritic: axon to dendrite
• Axosomatic: axon to cell body
• Axoaxonic: axon to axon
• Dendrodendritic: dendrite to dendrite

Gray’s Type I and II Synapses

• Type I: Asymmetrical, excitatory
• Type II: Symmetrical, inhibitory

The Neuromuscular Junction (NMJ)

• The NMJ is a synapse between the axons of motor neurons in the spinal cord and skeletal muscle
• Studies of the NMJ have established the principles of synaptic transmission
• The axons of the autonomic nervous system innervate glands, smooth muscle, and heart

Explore the intricate processes of quantal analysis and synaptic integration in this neuroscience quiz. Delve into the mechanisms of EPSP summation, the role of dendritic properties, and how these factors contribute to neuronal communication. Test your understanding of how neurotransmission and electrical signals interact within the neuromuscular junction and CNS.