Neurophysiology: Electrical Signals in Neurons/synapse

Neurotransmitters and Their Effects

• Same neurotransmitter can have different effects depending on the receptor it binds to
• Acetylcholine (Ach) binds to ionotropic and metabotropic receptors:
  • Ionotropic receptors (e.g., nicotinic acetylcholine receptors) allow influx of positively charged ions, leading to depolarization and excitatory effects
  • Metabotropic receptors (e.g., muscarinic acetylcholine receptors) trigger intracellular signaling cascades, leading to inhibitory effects

Neurotransmitter Removal

• Neurotransmitters can be removed from the synaptic cleft by:
  • Diffusion
  • Enzymatic degradation
  • Uptake into cells (reuptake or uptake into neighboring neuroglia)

Action of Drugs on the Chemical Synapse

• Drugs can:
  • Increase leakage of neurotransmitter from vesicle to cytoplasm
  • Increase neurotransmitter release into the cleft
  • Block neurotransmitter release
  • Inhibit transmitter synthesis
  • Block neurotransmitter reuptake
  • Block cleft enzymes that metabolize neurotransmitters
  • Bind to receptors on the post-synaptic membrane
  • Inhibit or stimulate second-messenger activity in the post-synaptic cell

Neurotransmitter Agonists and Antagonists

• Neurotransmitter agonists:
  • Mimic the action of endogenous neurotransmitters
  • Enhance neurotransmission
  • Bind to receptors on the post-synaptic neuron, leading to an excitatory response
  • Examples: L-DOPA (levodopa) for treatment of Parkinson's disease
• Neurotransmitter antagonists:
  • Block the action of endogenous neurotransmitters
  • Bind to receptors, preventing the neurotransmitter from exerting its usual effect
  • Result in inhibitory responses
  • Examples: Haloperidol for treatment of Schizophrenia

Neuromodulators

• Modulate synaptic transmission by influencing the release or reuptake of neurotransmitters
• Examples: Opioids, which can alter the electrical properties of target neurons and induce pain relief, euphoria, and other effects

Ion Channels

• Types of ion channels:
  • Leak channels
  • Ligand-gated channels
  • Mechanically-gated channels
  • Voltage-gated channels
• Ion channels open and close due to "gates" that can seal the channel pore shut or open it up
• Ion channels allow specific ions to move across the plasma membrane down their electrochemical gradient

Resting Membrane Potential

• Determined by:
  • Unequal distribution of ions across the plasma membrane
  • Selective permeability of the neuron's membrane to Na+ and K+
  • Na+/K+ pump
• Net flux of ions across membranes depends on both the concentration gradient and the electrical difference (electrochemical gradient)

Graded Potentials

• Small, transient changes in membrane potential confined to a small region of the plasma membrane
• Provide signaling in short distances
• Can be depolarizing (excitatory) or hyperpolarizing (inhibitory)
• Magnitude of the transient changes in membrane potential can vary
• Dependent on changes in membrane permeability to ions (ligand-gated ion channels)

Action Potentials

• Sequence of rapidly occurring events that decrease and eventually reverse the membrane potential (depolarization) and eventually restore it to the resting state (repolarization)
• Large changes in membrane potential of excitable cells only
• Membrane potential can change from -70mV to +40mV
• Depolarization, overshoot, repolarization, hyperpolarization, and return to resting membrane potential

Mechanism of Action of Action Potentials

• Initiated at the axon hillock (trigger zone)
• All-or-none event
• Depolarization needs to exceed the threshold potential
• CNS physiology and electrical signals in neurons

Electrical Signals in Neurons

• Information is carried within neurons and from neurons to their target cells by electrical and chemical signals
• Excitable cells communicate with each other via action potentials or graded potentials
• Action potentials allow communication over short and long distances, while graded potentials allow communication over short distances only

Synapse

• Anatomically specialized junction between two cells
• One single neuron can synapse onto many other post-synaptic cells (divergence)
• Many synapses from different presynaptic neurons can synapse with a single cell (convergence)
• Functional anatomy of the nervous system synapse:
  • Electrical synapse (gap junction)
  • Chemical synapse (operates through the release of neurotransmitters)