Bio 351 - Lecture 5 Notes
Action Potential Patterns Dictate Patterns of Neurotransmitter Release
Membrane Potential: The difference in electric potential between the interior and exterior of a cell; measured in millivolts (mV). It is maintained by an unequal distribution of ions (primarily Na+, K+, Cl-) across the membrane, established by ion pumps (like the Na+/K+ pump) and selective ion channels. The resting membrane potential is typically negative (e.g., ) meaning the inside of the cell is more negative than the outside.
Example values: 20 mV (depolarized), -20 mV, -40 mV (closer to threshold), -60 mV, -80 mV (hyperpolarized).
Key Concepts:
Stimulus initiates the response in neurons, causing a change in membrane potential.
Receptor detects the stimulus, often specialized proteins that convert various energy forms into electrical signals or bind to chemical messengers.
Afferent Neuron (sensory neuron) transmits signals from the periphery towards the central nervous system (CNS).
Graded Potential: A change in membrane potential that is localized, can be depolarizing or hyperpolarizing, and its amplitude is proportional to the strength of the stimulus. They decrement over distance and time.
Trigger Zone (axon hillock): The area of the neuron where action potentials are initiated if the sum of graded potentials reaches the threshold potential. It contains a high density of voltage-gated sodium channels.
Threshold: The critical membrane potential (typically around ) that must be reached for an action potential to occur. It triggers a rapid, regenerative opening of voltage-gated sodium channels.
Action Potential: A rapid, transient, all-or-none change in membrane potential that propagates without decrement along the axon. It involves depolarization (Na+ influx), repolarization (K+ efflux), and hyperpolarization (overshoot).
Neurotransmitter Release occurs during the action potential's arrival at the axon terminal, specifically during the depolarization phase of the action potential which opens voltage-gated calcium channels.
Cell Body (soma): Contains the nucleus and most organelles of the neuron, responsible for protein synthesis and metabolic support.
Axon: A long, slender projection that conducts electrical impulses (action potentials) away from the cell body towards target cells. Myelin sheaths facilitate faster conduction.
Axon Terminal (synaptic bouton): The distal end of the axon, specialized for transmitting signals across a synapse by releasing neurotransmitters.
Synapses in Neural Communication
Types of Synapses: Synapses are specialized junctions where neurons communicate with other neurons or effector cells.
Axodendritic Synapses: Connections from the axon terminal of one neuron to the dendrite of another neuron, often at dendritic spines. These are the most common type.
Axosomatic Synapses: Connections from the axon terminal to the cell body (soma) of another neuron.
Axoaxonal Synapses: Connections from the axon terminal of one neuron to the axon of another neuron, often near the axon terminal. These can modulate neurotransmitter release from the postsynaptic axon terminal (e.g., presynaptic inhibition or facilitation), affecting its influence on subsequent neurons.
Dendrodendritic Synapses: Connections between the dendrites of two neurons. These are less common and often involved in local circuit modulation.
Somatodendritic Synapses: Connections from a dendrite to a soma, also less common.
Electrical and Chemical Synapses
Electrical Synapses:
Signal transmission occurs via Gap Junctions, which are direct cytoplasmic connections between adjacent cells. These junctions are formed by complexes of proteins called connexins, forming a channel that allows small molecules and ions (like Ca2+, cAMP, ATP) to pass directly from one cell to another.
Characterized by very fast, bidirectional transmission and minimal synaptic delay.
Found in regions of the brain responsible for functions like synchronized neuronal activity (e.g., eye movement, respiration), emotions, and memory. They are also prevalent in cardiac muscle and certain smooth muscles.
Most abundant in embryonic nervous tissue, playing a role in neural development and circuit formation.
Chemical Synapses:
Use neurotransmitters that cross the synaptic cleft, a fluid-filled space (typically 20-40 nm wide) separating the presynaptic and postsynaptic neurons. This distance introduces a synaptic delay.
Presynaptic Neuron: Contains synaptic vesicles filled with neurotransmitter, which are released into the synaptic cleft upon stimulation.
Postsynaptic Neuron: Possesses specialized receptors on its membrane that bind to the neurotransmitter, leading to a change in its membrane potential (postsynaptic potential) or intracellular signaling. Chemical synapses allow for complex modulation, integration of signals, and are crucial for learning and memory.
Mechanism of Neurotransmitter Release
Calcium Ions (Ca2+) and Neurotransmitter Release:
Action Potentials arrive at axon terminals, causing depolarization of the presynaptic membrane.
This depolarization opens Voltage-Gated Ca2+ Channels (specifically N-type or P/Q-type calcium channels) embedded in the presynaptic cell membrane.
Ca2+ enters the presynaptic neuron from the extracellular fluid, as the intracellular Ca2+ concentration is normally very low. This Ca2+ influx acts as a critical signal.
Increased intracellular Ca2+ concentration signals neurotransmitter vesicles to move towards the active zones of the presynaptic membrane. Ca2+ binds to proteins like synaptotagmin, which acts as a Ca2+ sensor facilitating membrane fusion.
Vesicles dock at the active zone, fuse with the presynaptic membrane, and release neurotransmitter via exocytosis into the synaptic cleft.
Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic cell membrane, initiating a response (e.g., opening ion channels, activating G-protein coupled receptors).
SNARE Complex in Neurotransmitter Release
Components of SNARE Complex:
SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor) proteins are a family of proteins that mediate membrane fusion in eukaryotic cells.
Key SNARE proteins involved in synaptic vesicle fusion include:
Synaptobrevin (VAMP): A v-SNARE (vesicle-associated SNARE) located on the synaptic vesicle membrane.
Syntaxin: A t-SNARE (target membrane SNARE) located on the presynaptic plasma membrane.
SNAP-25: A t-SNARE (Synaptosomal-Associated Protein, 25 kDa) also located on the presynaptic plasma membrane.
These proteins are essential for the docking, priming, and fusion of synaptic vesicles with the presynaptic membrane, facilitating the highly regulated release of neurotransmitters.
Fusion Steps:
SNARE complex assembly: Upon Ca2+ influx, synaptobrevin on the vesicle interacts with syntaxin and SNAP-25 on the presynaptic membrane, forming a tight four-helix bundle. This assembly pulls the vesicle and plasma membranes close together, overcoming the energetic barrier to fusion. Chaperone proteins assist in the initial stages.
Fusion pore opens: The zipping up of the SNARE complex induces curvature and subsequently leads to the formation of a transient fusion pore, allowing neurotransmitter to rapidly efflux from the vesicle into the synaptic cleft.
SNARE complex disassembly: After fusion, a protein complex involving NSF (N-ethylmaleimide-sensitive factor) and SNAPs (Soluble NSF Attachment Proteins) utilizes ATP hydrolysis to uncoil and dissociate the SNARE complex, preparing the proteins for further rounds of vesicle fusion and recycling.
Types of Endocytosis in Neurons
Neurons employ various endocytic mechanisms to retrieve fused vesicle membranes and maintain the presynaptic terminal's function during ongoing neurotransmission.
Endocytosis Types:
Clathrin-mediated Endocytosis (CME): The classic pathway for recycling synaptic vesicles. It involves the formation of a clathrin coat around the newly endocytosed membrane patch. Dynamin, a GTPase, then